Sample treatment with focused acoustic energy

FIELD: physics, acoustics.

SUBSTANCE: group of inventions relates to an apparatus for irradiating a sample with focused acoustic energy, a device which is part of said apparatus, a cartridge for said device and a method of irradiating a sample with focused acoustic energy. The apparatus comprises a device, a cartridge, a completely solid-state connector and a source for generating acoustic energy. The cartridge has a chamber for receiving a sample, and the completely solid-state connector provides a completely dry coupling of acoustic energy between the source and the cartridge. The device and the cartridge are adapted for inserting the cartridge containing a sample into the device and are separable, and the focused acoustic energy is focused high-intensity ultrasound. The device has a source for generating acoustic energy and the cartridge has a chamber for receiving a sample.

EFFECT: improved sample processing.

17 cl, 24 dwg

 

The technical field TO WHICH the INVENTION RELATES

The present invention relates to the treatment of samples by focused sound energy. In particular, the present invention relates to an apparatus for irradiating the sample with focused acoustic energy for treatment of the sample and the method of irradiating the sample with focused acoustic energy for treatment of the sample.

The prior art PRIOR to the present INVENTION

In recent years progress has been made in many aspects of the devices 'sample - in, result out" (sample-in, result-out) also known as common microanalysis (microTAS) or lab-on-chip (lab-on-a-chip), for a number of reasons for the increasing interest in the use of in vitro diagnostics (IVD). For example, the integration and miniaturization result in systems requiring relatively small acceptable risk of contamination of the sample with high sensitivity and short test time and reduced cost of test. In addition, between the sample inlet and the result should require minimal operator intervention. Operator intervention can be performed relatively untrained operator at moderate requirements to the conditions of operation.

Known methods of processing samples with acoustic energy mo�ut not be suitable for certain uses, such as molecular device, since after sonic treatment cannot be established, the difference between the leakage from the cartridge, having liquid inside the sample, and the fluid used by the device. This may be an unacceptable result of processing within these devices with the use of such a connection of liquids.

In addition, pre-processing function that includes complex operations such as, for example, mixing, runs a separate and independent manner relative to other processing functions. This is contrary to the General tendency in this area to further miniaturization and integration. More seriously, this contradicts, for example, the requirements of the hospital or laboratory, which is to have the system actually small in size, due to the very limited space available in these places.

In addition, molecular diagnostic tests often include methods with complex piezometric, complex control systems and complex electrical actuators. These techniques are expensive, require considerable technical support and also take up much space.

Summary of the INVENTION

The purpose of this invention is to provide improved handling of samples.

This goal can be realized �through the subject matter of the invention in accordance with one of the independent claims. Embodiments of this invention are described in dependent claims.

Definitions and abbreviations:

You must specify that for purposes of this invention will be used the following definitions and abbreviations:

Dry link:

The term "dry connection" will be used in this invention as the full passage of sound energy through a substance, not a liquid, from the source to the sample.

Sound energy:

The term "sound energy" was used in reference to the present invention as including such terms as acoustic energy, sound waves, sound pulses, ultracytochemical energy, ultrasonic waves, ultrasound, shock waves, sound energy, sound waves, acoustic pulses, pulses, waves, or any grammatical forms of these terms.

Focal area and focal point:

"Focal region" or "focal point" as used in this invention means an area where sound energy converges and/or hits the target or sample, although this area is not necessarily a single focal point.

Device:

The term "device" in this invention includes devices for molecular diagnostics and other devices�. Types of application devices may be, for example, healthcare/life Sciences, food industry, veterinary and forensic applications.

Sample:

It should be explicit that the term "sample" may include samples for molecular analysis, processed by the device in accordance with the present invention. For example, blood, artificial blood, urine, a material obtained by aspiration, samples with similar water viscosity, heterogeneous samples or samples on the media, such as bronchoalveolar lavage (BAL), saliva, tracheal material obtained by aspiration of cerebrospinal fluid (CSF) smear and/or brush with a pathogen. However, this does not mean that any other kind of matter, solid, liquid, gaseous, or any combination thereof, are not permitted for use as a sample and irradiation of the focused acoustic energy according to the present invention.

NA:

The code "NA" will be used for any nucleic acid.

Source:

For purposes of this invention, the term "source" will be used as a synonym of the term "Converter". In addition, any other equipment that has the possibility of emission of sound energy, as defined for purposes of this invention, with�erida in the source.

The path of propagation:

The phrase "pathway" describes in relation to the present invention the path of sound energy from the source via any combination of at least the connector and the cartridge to the sample. Other elements, such as lenses, additional connectors may be on the path of propagation. Thus, the distribution of the sound energy passes through the intermediate contact layers of these different elements. In addition, may contain other layers, such as, for example, the acoustic window or front-end environment.

Attenuation:

The term "attenuation" in this invention refers to the decrease in the intensity of the generated sound energy. This may be due to, for example, reflection, absorption, diffraction, or any combination of these.

Processing the sample:

The term "treatment" or "training" is used in this invention to describe the interaction of a focused acoustic energy to the sample. By focusing the sound energy in the sample different in special ways in the sample are called akusticheskii and/or akustisches reaction to create functionality such as, for example, mixing, dispersing, mixing, elution from strokes or brushes, �atijenii, the lysis or release of cells. Thus, the definition of "processing" also describes akustisches and/or akusticheskii interaction during the process called "pre-processing". In other words, "treatment" includes, among other features, "pre-processing" of the sample.

Working chamber:

The expression "working chamber" will be used the same as "the chamber" and "chamber the cartridge".

Ultrasound:

The terms "ultrasound" and "ultrasonic" are used for cyclic sound pressure with a frequency between 20 kHz and 100 kHz.

Focused high intensity ultrasound (HiFu):

The term "HiFu" will be used in this invention as a focused acoustic field with nominal frequencies in the range from 0.2 MHz to 10 MHz, with amplitudes chosen so that they were sufficient to create shock waves of high pressure and/or cavitation in the focal area. The dimensions of the focal zone (length and diameter) depend on the type of source Converter (for example, natural focusing plane or forced focus conical/spherical source converters). The approximate scale length for nominal frequency range is (sub)mm.

System sample on �course - the result output:

A system in which the sample is placed (e.g., biological sample), performs all the necessary steps of preparation, to prepare it for data definition any kind, performs the determination and provides the results of the determination. For example, there may be provided a device for molecular analysis of samples, such as, for example, blood or other cells that provides all the essential stages of analysis, from feeding a natural, unprocessed sample prior to the issuance of the analysis results.

Lenses:

For purposes of this invention, the term "lens" can be used as a component or system that provides for the dispersion or convergence of sound energy. Any substance that can affect the characteristics of the propagation of the generated sound energy, must be regarded as included within the term "lens".

The boundary/interface environment:

For purposes of this invention the path of propagation of sound energy may contain multiple components, such as source, fully solid coupler and the cartridge. In order to describe the transitions or the zones in which these different elements of the pathways related to each other through physical contact, uses the terms "boundary" and "�nteresna environment". For example, if the connector is in physical contact with the cartridge, the interface environment of the connector describes the material used in the connector in the area of the connector is brought into contact with the cartridge.

Connector:

The term "connector" will be used in this invention as an element that is part of the path of propagation of sound energy and can transmit, together with other elements, the sound energy from the source to the cartridge. In addition, the term "connector" is used similarly to the term "fully solid-connector".

Solid gel:

For purposes of this invention "solid gel" contains only the gel-forming material. It is completely solid state and at the same time is a gel. Liquid substances are completely eliminated in a solid gel. Accordingly, water or hydrogel is fixed when using a solid gel. Thus, the term "gel" as used in this invention is used similarly to the term "solid gel".

It should be noted that the variants of implementation, described later, similarly relate to a device for irradiating the sample with focused acoustic energy and method of irradiating the sample with focused acoustic energy. About� various combinations of the embodiments may occur synergistic effects, although they may not be described explicitly or in detail.

Further it should be noted that all embodiments of this invention related to method, can be performed in the order of steps described, but it should not be seen as the sole and mandatory order of the method steps. All other orders and combinations of the method steps disclosed by this assertion.

In accordance with the first aspect of this invention provides a completely solid connector for the dry connection of sound energy between the source and the cartridge. Accordingly, in the first exemplary embodiment of the present invention presents a device for irradiating the sample with focused acoustic energy to treat the sample, wherein the device comprises the device, the cartridge is fully solid state connector and a source for the generation of sound energy. In addition, the cartridge has a chamber for receiving the sample, and a completely solid connector provides fully dry connection for sound energy between the source and the cartridge. The device and the cartridge are adapted for insertion of the cartridge into the device, wherein the cartridge and the device are shared.

Next will be explained in detail possible additional features and advantages of the device�VA in accordance with the first exemplary variant implementation.

In other words, by inserting the cartridge into the device creates a dry pathway for focused sound energy from the source to the sample. All the various dry components of the device, cartridge, fully solid-connector's source and, thus, are connected completely dry, after insertion of the cartridge into the device. The connector typically transmits sound energy from one end to the other end. Should be a clear way to indicate that a completely solid connector is located in the device in such a way that it complements or completes the path of propagation of the acoustic energy between the source and the cartridge in a dry way. In other words, the propagation path contains completely before inserting a solid first connector dry partial path distribution and the third partial path of propagation. By inserting the connector between the two parts is missing the second partial path. The full path of propagation, for example, may be formed, firstly, of a material that is attached to the focusing transducer, secondly, of a polymeric connector and, thirdly, the foil between the connector and the cartridge. Thus, completely dry the link between the source and the cartridge. Accordingly, the totally�'yu solid connector should not itself form all the way distribution however, if it is desirable, exemplary variant of implementation of the present invention can implement it.

Therefore, eliminating the use of water or hydrogel or gel containing a liquid substance. Accordingly, after completion of the radiation of sound energy can be established a clear distinction between the possible leakage from the cartridge containing the liquid substance, and a binding medium. In other words, a situation with a high risk of contamination due to leakage from the cartridge can be recognized by the user of the device more clearly and more quickly.

When the device and the cartridge are completely different components, they are physically separated, or at least separable sample volume to be processed can be selected by selecting different cartridges. In addition, the chamber of the cartridge may not be completely filled with sample and have, respectively, an additional air layer inside the chamber above the sample. This can lead to several technical advantages compared to the so-called flow-through systems. An example of the advantages of the air layer above the sample is that by HiFu can be created vigorous stirring, providing the ability to process sample volumes are much greater than the volume of the focal zone. For example, simply�PTO create a fountain of liquid sample by using HiFu irradiation may be provided with a mechanism for mixing with the circulation of the liquid sample, which is inevitable in the cycle of spouting. Thus the focal zone of the HiFu energy creates a fountain can be quite small compared to the sample size, however, nevertheless, by means of HiFu is initiated by the mixing process using a fountain. Accordingly, this exemplary embodiment of the present invention can be eliminated the need for irradiation of the entire volume of sample that needs to be mixed. In other words, a large sample can be processed by a relatively small device.

In addition, HiFu can create a fountain that can be used to create cavitation at relatively low (lower) power. Centers cavitation can be introduced into the sample drops of the fountain, returning to liquid, which can reduce the threshold power compared to the homogeneous cavitation in water by an order of magnitude. In other words, through education of the fountain from the sample (for example, when the sample is a liquid) minimum power for the transducers and, accordingly, the minimum audible energy that must be radiated from the source, can be reduced. This may provide the advantages described in connection with the invention.

In other words, the fountain, in addition to stirring about�of ASCA and a decrease of the threshold power of cavitation, can be used for cooling the sample, as the fountain creates a much larger contact surface of the sample with ambient air inside the cartridge.

Physical separation of the cartridge and the device can lead to non-integrated system, which means that the source connector and the cartridge can be selected and applied to measure independently of one another. In other words, the boundary between the three constituent parts of the system (source, a connector and a cartridge) can be made independent of the choice of these three component parts, if this choice corresponds to the boundary of the section.

Due to the fact that the size of the cartridge and the camera does not depend on the size and shape of the source and connector, you can increase the volume of the cartridge without having to change the acoustic characteristics of the device. The disadvantage of flow systems compared to this variant implementation of the present invention may be that in their case it is impossible to increase the camera without the need to increase also and Converter.

In addition, you can be confident in focusing at the focal area and eliminate the dependence on the interaction of sound energy with the wall of the chamber. In other words, the chamber wall is not used as a Converter. In contrast to these known si�, it should be taken into account what is the resonant frequency of the chamber walls depend on the geometry and material properties. These systems must coordinate them with the frequency of the source. Because it does not depend on interactions of the acoustic field and the walls in the manner described, the camera zoom can be done regardless of the choice of the Converter.

Since the cartridge is physically separable from the device, the cartridge may be disposable, consumable and replaceable cartridge that may lead to inexpensive system for analysis of a sample with focused acoustic energy. After sample processing cartridge may be discarded without discarding the source or connector. Accordingly, possible by using a dry connection is the provision of a plurality of measurements of a single device and one solid connector and one source to a plurality of different cartridges with different samples.

The device can also contain a lens for focusing the generated acoustic energy in the sample.

In addition, the irradiation of a sample with focused acoustic energy causes the processing of the sample.

Source or transducer may be flat or curved piezoelectric transducer operating at frequencies between kHz and up to megahertz. The diameter of the Converter can� be, for example, between 5 mm and 35 mm, to reply to the interval volume (0.2 ml - 10 ml), the corresponding process cartridge. Focal length transducers can vary from 5 mm to 80 mm. the Input electric power Converter may vary from 2 watts to 100 watts. In accordance with this exemplary variant of implementation of the present invention, the processing of the samples is possible at lower capacity compared with the corresponding known technology. Accordingly, eliminates the heating due to absorption of sound energy by the environment, especially of matter between the source and the sample, making possible the introduction of a dry connection.

The Converter can operate in continuous mode or in pulsed mode. The signal applied to the Converter may have a different and changing forms: for example, sinusoidal, rectangular, triangular, or any combination thereof. The frequency can be further adjusted to compensate for the frequency shift due to heating or to change the focal length.

The cartridge may have one of the following characteristics: can be disposable, expendable, replaceable, can contain a single camera or multiple cameras may contain a single sample or multiple samples, to have industrial application. The material of the cartridge can be, e.g.�measures polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polymethylpentene (PMP), polymethylmethacrylate (PMMA), polycarbonate (PC) and polystyrene (PS), not limited to.

In addition, the cartridge is also a component that is physically independent from the connector. Accordingly, the ink cartridge is a great component and separable from the device and also from the connector. This exemplary variant of implementation of the present invention does not exclude the fact that the connector is placed or mounted on the cartridge or the device and includes this feature.

The main advantage is that all desirable and necessary treatment of the sample can be performed in a single chamber of the cartridge. In addition, all processing applied sound energy can be made in accordance with the principle of "sample - in, result out" with all the necessary conversions in the action happening from a single source device. By means of focused acoustic energy of the sample can be processed using several different features, such as sample pretreatment and lysis in a single cell, which is the working chamber. In particular, HiFu can be used for these processes.

To achieve in�high intensity sound energy into the receiving chamber in the cartridge and accordingly, in the sample), it is preferable that the quality of the source or focus of the transducer and/or lenses was sufficient to attenuation of acoustic waves in materials on the path of propagation of the sound energy was quite low, which means low acoustic impedance and/or a small thickness, and the reflection at the interfaces between materials in the path of propagation of the sound energy was quite low, which means to dry the connector that the thickness and roughness of the two contacting layers must be sufficiently small. This exemplary variant of implementation of the present invention meets these requirements.

Energy can be supplied to the source from the device through, for example, conclusions or brushes. Completely solid state, the connector may contain different portions, parts or segments.

In addition, it may dry the bond that for the micro-scale contact between, for example, the source and the connector (first layer) and/or the connector and the cartridge (the second layer) can approach the condition of direct contact, in other words, such a heavy weight as possible to achieve effective dry connection. Accordingly, the surfaces of the two layers can be conformal in the microscale or the nanoscale, how the who�one, to minimize or eliminate air pockets between the two layers of dry contact.

In other words, to minimize or eliminate air pockets, the device can be met the following requirements: the surface roughness can be small enough for the source, connector, cartridge, a completely solid connector and interface environment. Also the materials used can be sufficiently "flexible" to achieve conformance. In this regard, the order of conformity can be considered as liquid>hydrogels>solid gels>rubbers>(elastic) films>thermoplastic polymer>thermoset materials, metals, ceramics and other solid materials.

Sound energy or sound radiation can propagate through the first part of the path unfocused and can then be focused inside the second part of the way to spread focused through a third of the way to the sample. It is also possible preceding or succeeding the focus.

The power required for the process of creating cavitation in the sample, can be reduced by this exemplary embodiment of the present invention, since the camera can be entered additional nucleation centers (for example, an element with a suitable high�Oh surface roughness, for example, the terminal) or may be created by a fountain. Drops, falling back from the fountain in the sample can reduce this threshold power. As the presented design provides both of these capabilities, low power HiFu can be used for the preparation and processing of the sample.

Since the required power can be reduced by this invention, it is possible to avoid additional refraction, created at high intensities.

In accordance with another exemplary variant of implementation of the present invention focused sound energy is a focused high-intensity ultrasound (HiFu).

Thus, the nominal frequency may be in the range from 0.2 MHz to 10 MHz, with amplitudes chosen in such a way as to be effective enough to create shock waves of high pressure and/or cavitation in the focal area. The dimensions of the focal zone may depend on the type of the source Converter. The approximate scale length for nominal frequency range is (sub)millimeter. In addition, can be used flat or curved piezoelectric transducer operating between 0.2 MHz and 10 MHz, or between 0.75 MHz and 3 MHz, or between 1 MHz and 2 MHz. The diameter of the Converter may be, for example, between 5 mm and 35 mm, �order to respond to the interval volume (0.2 ml - 10 ml), the corresponding process cartridge. Focal length transducers can vary from 5 mm to 80 mm. the Input electric power Converter may vary from 0.5 watts to 100 watts.

In other words, this exemplary embodiment of the present invention may be used as a molecular device with HiFu for the treatment and/or molecular analysis of samples. In this regard, the liquid should not be used for the transmission of sound energy from the source to the sample. Accordingly, the risks of contamination of the fluid can be reduced, and by disposable or consumable cartridges can be provided a simple, cheap and quick way of measuring characteristics of the sample plus sample preparation through the device and, accordingly, through HiFu.

Due to the relatively short wavelength of HiFu compared to ultrasound can be improved focusing on the area of the smaller sizes. This leads to the advantage of the miniaturization.

In addition, different distinct forms the focal area can be used for processing the sample through HiFu.

Because HiFu provides the user with the ability to process a sample, for example, with such functionality, as mixing with the reagent, the blood circulation attention: t�I, the release of cells, pathogenic microorganisms and the matrix material of the stroke, the release of cells, pathogenic microorganisms and the matrix material from the brush, liquefaction, incubation of the sample with the reagent at room temperature or elevated temperature, shaking, mixing; mixing, extraction, extraction of nucleic acid (NA), generation of the flow, homogenization of the sample, separation by centrifugation, and any combination thereof, lysis, lysis of microorganisms, incubation of the sample with the reagent at room or elevated temperature, and any combination thereof, that creates a huge variety of uses for the device.

Furthermore, the known systems can be limited by the physics of the process, because the actual miniaturization of the ultrasound transmitter may be impossible known system may, accordingly, be limited to approximately 100 mm. This variant implementation of the present invention can be miniaturization to a size less than 100 mm.

Further, another disadvantage of known systems may be the fact that the resonant frequency of the ultrasonic camera depends on design and material and correspond to the selected transmitter frequency ultrasound. Manufacturing tolerances may need to include this dependency. In contrast, all�I resonant frequency of the device may not be taken into account as described above.

In addition, other devices that use sound energy can be limited by the chamber of small volume, as in accordance with the basic physical laws of mechanics, the increase in size means a reduction of the resonant frequency of the chamber or system. In parallel, existing in the specification of the sample requirements for the ultrasound frequency can, therefore, make the camera size. This may limit the range of uses of such a known device.

In contrast, the presented system is not integrated, in which the cartridge is physically independent, i.e. separated from the source and connector, as described above. It may be that the resonant frequency of the chamber should not be taken into account when you select the desired size of the cartridge or camera. This is an important advantage in comparison with known technology.

In addition, this exemplary variant implementation provides the ability to avoid, if necessary, flow-through methods, which can complicate the integration with incubation at elevated temperature. In addition, running these methods may have a need for the provision of some types of granules in the cells. However, in the case where the flow may be desirable, this idea can deliver it.

Dr�in other words, this exemplary variant of implementation of the present invention differs from the technique with ultrasound acting on the wall of the chamber. In these known systems, the resonant frequency depends on the geometry and/or material of the device.

In addition, unlike flow-through systems that use homogeneous cavitation, power can be reduced in this exemplary variant implementation, since this exemplary embodiment of the present invention may be applied to the formation of air layer in the camera, which makes possible the introduction of centers of nucleation or the formation of the fountain, as described above. By means of additional nucleation centers, such as the rod is introduced into the chamber, or by means of the described fountain power threshold for the initiation of cavitation can be reduced. In addition, you may be given the opportunity of incubation of the sample, although not all of the fluid sample must be in the focal area.

This may allow the user to use smaller transformers and smaller powers, that provides the possibility of including a completely solid connector or a dry connection. In addition, can be alleviated combination with incubation.

In addition to this exemplary embodiment be implemented thr�of this invention is the possibility of using various additional functions for example, elution of the stroke in the working chamber. Because HiFu is used with dry connection, it allows you to determine the leakage of the cartridge, and therefore, contamination can be detected at an early stage.

In accordance with another variant implementation of the present invention the source is part of the device or part of a cartridge.

In the first example of this embodiment of the source can be enabled in the device. Consequently, multiple cartridges can be irradiated one by one, through one and the same source of sound energy. Accordingly, the measurement results for different cartridges may be more comparable and reliable because they can be excluded deviations originating from different sources.

In the second example of this embodiment of this invention the source is part of the cartridge. For example, the cartridge may be provided with a source and a fully solid coupler disposed between the source and the cartridge. For example, they can be glued together into a single node. Can also be used other opportunities to consolidate. By including this node in the device provides electrical connection between a node supplying power to the source. Accordingly, in this embodiment of the present invention creates fully�TEW dry connection.

By integrating the source with the cartridge of possible pre-selection or pre-adaptation of a particular source for a particular target dimensions. Accordingly, in combination with the device can be used with various types of cartridges are specifically selected as a source for these cartridges and for specific measurements using a single device. This means an increase in the area of operation of the device. In addition, the cartridges and springs mounted on the cartridge may be disposable, and thus, may be provided cheap and neoslojnennoe solution for handling different samples in different cartridges with different sources, connected through a single device.

In accordance with another exemplary variant of implementation of the present invention, the device and the cartridge are arranged in such a combination that by inserting the cartridge into the device forms a pathway for the transmission of sound energy from the source to the sample, wherein the propagation path does not contain liquids.

In other words, the relationship of the cartridge and the instrument during the insertion process leads to the path of propagation with dry coupling. Therefore, the corresponding surfaces of the device and the cartridge are brought into contact during insertion, and they may have a form to create, for example, the path with a closed shape or path with an interference fit. In addition, fitting the shape of the contour of the device and the cartridge is additionally designed for the application of pressure between these elements, and can be provided with an additional connector. In other words, only solid materials and gaseous materials such as air pockets are present on the path of propagation of sound energy.

In accordance with another exemplary variant of implementation of the present invention, a completely solid connector is formed from material selected from the group consisting of a solid gel, a rubber, an elastic film, a material based on polymer, thermoplastic polymers, the polymer having a low attenuation of sound vibrations, metal, semiconductor, ceramic, polypropylene, aluminum and multilayer packages of these materials.

Should be a clear way to indicate that a completely solid connector can be formed of a material based on polymer.

The materials used may have the characteristics of elasticity, which provide the opportunity to align the connector with the shape of the component devices, such as cartridge or source. Accordingly, the material is completely solid-connect�I can be chosen that air pockets on any boundary of the distribution is minimized or eliminated in order to achieve effective dry connection. In addition, a fully solid coupler may also contain the above materials as partial components, and other materials not mentioned may be contained in a fully solid coupler.

The calculations showed that the package could increase the amount of energy that would be transmitted to the reception site, but at the expense of a more complex connector. In other words, can be used for the coordination of acoustic resistance. Accordingly, a fully solid coupler may contain several components, which together result in a complete and effective dry connection, sound energy from the source to the sample.

In accordance with another exemplary variant of implementation of the present invention the cartridge includes an acoustic window, acoustic window made of flexible film, and completely solid state, the connector is physically in contact with the acoustic window by inserting the cartridge into the instrument.

To achieve high intensity focused acoustic energy in the receiving chamber in the cartridge that contains the sample) may be significant that the attenuation in the material�x " in the path of the HiFu is quite low. In addition, air pockets should be minimized or eliminated by the roughness of the surfaces is small enough. Can also be used materials which are sufficiently flexible. These requirements can meet the acoustic window, which is made of a flexible material, such as plastic film. Thus, the plastic film can adapt its shape during insertion of the cartridge into the device in accordance with the shape of the contact surface of the cartridge or form a completely solid connector.

Acoustic window of the cartridge may be large enough cross-section of the cone HiFu at a given distance acoustic Windows completely housed in the window. The acoustic window may be flat or curved. An acoustic window made of a thin layer of polymer with low attenuation, for example, polypropylene (PP), polymethylpentene (PMP). It is also important that the rest of the walls of the chamber for lysis below the liquid level may be sufficiently thin to reduce acoustic losses and to limit heating of the body of the camera.

In accordance with another exemplary variant of implementation of the applied contact pressure between a fully solid coupler and the cartridge, wherein the contact pressure is created by men�her least one method from the group including the application of excess pressure in the chamber of the cartridge, the application of local pressure from the outside of the cartridge and the cartridge pressing and fully solid-one connector with respect to the other by application of force.

The contact pressure between the solid connector and the surface of the cartridge is applied in such a way as to be sufficient to remove air or air pockets at the interface or at any intermediate layer on the path of propagation of sound energy. A possible solution may be pressed, for example, solid connector, convex to flat cartridge, despite the fact that the material of the cartridge is flexible enough to take a shape corresponding solid-state connector. In addition, the connector can also have the same flexibility.

Another exemplary variant of implementation can be the solution with a dry boundary containing a smooth spherical or conical HiFu transducer and the flexible film cartridge.

Thus, the contact pressure causes a force that compresses at least three components, a source, a connector and a cartridge with one another in such a way that can be minimized air pockets between some or all of the contacting surfaces�of challenges. So mainly smooth and flexible materials can be used for these surfaces.

In accordance with another exemplary variant of implementation of the present invention is completely solid state, the connector has a first contact surface for contacting the acoustic window, and the cartridge has a second contact surface for contacting the acoustic window. In addition, at least one surface of the first contact surface, the second contact surface and the acoustic window has a value of surface roughness selected from the group comprising a value less than 0.5 μm, less than 1 micron and less than 2 microns.

Through this embodiment of this invention, air pockets and, accordingly, losses in the transmission of sound energy can be minimized or eliminated.

The interface environment between the device and the cartridge to allow the transmission of sound energy through a dry boundary may be made of a material with low attenuation, such as rubber (for example, RT 615), (elastic) film (e.g., polypropylene (PP), thermoplastic elastomer based on polypropylene, polymethylpentene (PMP) or thermoplastic polymer (e.g., polypropylene (PP)). Layer at the interface may be part of a device or �artridge. For example, the bottom layer of the cartridge in contact with the connector, may also be simultaneously interface environment.

In accordance with another exemplary variant of implementation of the present invention, the propagation path has an acoustic impedance gradient, wherein the gradient monotonically decreases in the direction from the source to the sample.

This implementation option can lead to additional loss of sound energy as a connection from one component to another component in the direction of spread can be improved due to the gradient of the acoustic impedance. By applying this profile acoustic resistance of the diffusion of the reflection and absorption of the focused acoustic energy can be reduced. This can lead to improved productivity or efficiency for a given power.

The acoustic impedance of the materials used on the path of propagation of sound energy is changed from a relatively high-side source to a relatively low-side sample/cartridge. In addition to this can be used basic laws of acoustics to optimize the election of the dimensions and material of the device and its components.

In accordance with another exemplary variant of implementation of this image�etenia fully solid coupler is selected from the group contains the connector, which is physically separate component placed between the source and the cartridge, the connector that is part of the source connector, which is part of the cartridge and any combination thereof.

For example, a possible configuration with a source, which is a piezoelectric transducer, combined with a metal lens on top of it, which has a polymer over the metal connector lenses. Also may be provided a curved source working simultaneously as a lens, together with a polymeric connector curved over the top of that source. The connector can be physically connected to the source or the cartridge, but may also be supported on top of one of these components by means of external pressure applied to these components. When you refer to below Fig.10-14 possibly a great variety of combinations of location and fastening of the connector between the source and the cartridge. The placement of the connector on the source, on the cartridge, on the lens, the second additional connector on an acoustic window through the various possibilities of fastening, such as a compressible, bonding, deposition connector on the component and any combination of them, are included in this variant implementation of the present invention.

In accordancewith another exemplary variant of implementation of the present invention additionally contains a lens for focusing the generated acoustic energy to the sample. Accordingly, the lens is selected from the group consisting of a lens, which is a physically separate component placed between the source and the cartridge, a lens that is part of the source, the source with the shape of the focus, which lens, a matrix of sources that generate focused acoustic energy, a lens forming part of the cartridge, a lens constructed of polymer having low attenuation of sound vibrations, metal filter, ceramic filter, polypropylene lens, aluminum lens, hybrid lens, and any combination thereof.

The lens may be made of polymer, metal or ceramic with low attenuation. From environmental considerations, the lens may be combined with a consumable cartridge and manufactured from polymer, such as polypropylene (PP).

As the first characteristics lenses lens provides the possibility of focusing the sound energy generated in the sample. In order to reduce transmission loss, the lens can be fixed at the source. For example, a metal lens may be mounted on a piezoelectric transducer, leading to the emission of the focused acoustic field. In addition, the matrix from multiple sources can be spatially positioned in such a way and have such an electronic actuator that the superposition of all the single and�rustichesky fields leads to a focused acoustic field. It's also possible that the lens is part of the cartridge, for example, is fixed to the cartridge. In addition, this example may also include the source, which is part of the cartridge.

To create multifocality also in this exemplary embodiment of the present invention may be used in a hybrid lens. Accordingly, this lens has at least two different emitting areas, which means that different emitting areas lenses differ from one another by at least one of the following components: shape, surface roughness, material and any combination thereof. Briefly summarizing the function of the hybrid lens, it should be noted that the incoming homogeneous acoustic field will be converted to a hybrid lens in an inhomogeneous acoustic field having, for example, two different focal area.

In accordance with another exemplary variant of implementation of the present invention in a single chamber cartridge pretreatment and lysis are applied to the sample through the focused acoustic energy. Consequently, the pre-treatment comprises a method selected from the group consisting of mixing with a reagent, circulation, release of cells, pathogenic microorganisms and the matrix material of smear, wysw�the recovery of cells, pathogens and the matrix material from the brush, liquefaction, incubation of the sample with the reagent and/or enzyme at room temperature or elevated temperature, shaking, mixing, stirring, extraction, extraction of nucleic acid (NA), the generation of flow, homogenization of the sample, separation by centrifugation and any combination of them. In addition, lysis is a method selected from the group consisting of mixing with a reagent, mixing with a reagent different from the reagent applied during pre-processing, circulation, the lysis of microorganisms, incubation of the sample with the reagent at room or elevated temperature or a temperature different from the temperature used during pre-processing, and any combination thereof.

It should clearly indicate that the combination of pretreatment and lysis in a single chamber by means of a focused sound energy coming from a single source, can be applied without providing a dry connection. A completely solid connector or path of propagation of a completely dry environment are not necessary.

Accordingly, the second feature of this invention is directed to the use of pretreatment and lysis of the sample p�means of focused acoustic energy in only one chamber of the cartridge, that is, in particular, in the same chamber. The approximate variant of the implementation of this feature of the present invention provides a device for irradiating the sample with focused acoustic energy to treat the sample, the device contains a device, cartridge and a source for the generation of sound energy. The cartridge has a chamber for receiving the sample. The device and the cartridge are adapted for insertion of the cartridge into the device. The cartridge and the instrument are separable. The device is designed in such a way that pretreatment and lysis were applicable to the sample in the chamber of the cartridge by means of focused acoustic energy.

In addition to this exemplary variant of implementation of this second features of the present invention also relates to a corresponding device for irradiating the sample with focused acoustic energy to treat the sample, the device comprises a source for generating acoustic energy. The device is adapted for reception of a cartridge, which is detachable from the device, this cartridge provides a chamber for receiving the sample. The device is designed so that when the cartridge is inserted into the device, pretreatment and lysis can be applied to the specimen in the chamber of the cartridge by means of focused acoustic energy.

Accordingly, in another about�m variant implementation is provided a cartridge, this cartridge unit for irradiating the sample with focused acoustic energy generated by the source to process a sample, comprises a chamber for receiving the sample. The cartridge is adapted for insertion into the device and is detachable from the device. The cartridge is designed so that, when inserted into the device, pretreatment and lysis were applicable to the sample in the chamber by means of a focused sound energy.

In addition, exemplary embodiments of the implementation of this feature of the present invention also relates to a corresponding method pretreatment and lysis of the sample in a single chamber by means of focused acoustic energy, such as, for example, HiFu coming from one single source, preferably, by means of such a device, and computer program element, characterized in that it is adapted when applied to control a device for pretreatment and lysis of the sample to cause the executing device of the stages of the corresponding method.

These exemplary embodiments of the implementation can, for example, to combine pretreatment and lysis in a single cell by applying odnofotonnogo HiFu, however, also possible to use a multi-focus HiFu. One�also about any combination with incubation.

In other words, can be eliminated manual steps necessary to perform a pretreatment of the sample by means of an exemplary embodiment of a device corresponding to the device and cartridge of the corresponding method and computer program element. Pre-processing is integrated into the cartridge, to increase the ease of application and to reduce the interaction of the fluid with the environment and the risk of contamination. In addition, the functions of pretreatment and lysis combined in a single chamber which can be subjected to HiFu and/or heated and/or cooled, to reduce the complexity, cost and size of the device, and procedures for joint processing and lysis. The functions of pretreatment and lysis mostly carried out without intermediate output of the sample from the chamber and/or mainly performed in a fully automated manner and/or predominantly performed sequentially or simultaneously.

This second feature of the present invention can be used for any application requiring pre-processing and/or lysis. Applications may not be limited to health, biomedical Sciences, food industry and veterinary medicine. This applies to any �the Ariant implementation of this invention.

Especially difficult to lyse microorganisms current state of technology of application of thermal lysis has several drawbacks. In contrast, this aspect of the present invention uses focused acoustic energy, mainly HiFu, to solve these problems. Through this fully integrated in vitro device for the preparation and detection system is provided for testing "sample - in, result out", especially for the detection of nucleic acid (NA), protein or cells. Furthermore, through the so-called Microsystems a complete analysis can be possible the analysis of nucleic acids, protein analysis and analysis of cells.

In addition, existing methods of lysis include shredding or destruction of the granules, which can here be avoided.

In General, protocols for the preparation of the sample nucleic acids are more sophisticated than the protocols of preparation of the sample of cells or protein. Although these aspects of the present invention may be applicable in the main part for the preparation of the sample nucleic acid, it is not limited to this.

For this reason, a separate solution with high flexibility requires adaptation to these variations in required pre-treatment. This aspect of the present invention meets these requirements by vysokoaktiven of flexibility with respect to protocols pretreatment and lysis.

It should be noted that the preferred embodiments of the other aspects of this invention should be considered as the preferred and disclosed variants of implementation in relation to this aspect and Vice versa.

In accordance with another exemplary variant of implementation of the present invention the device is adapted such that it generates at least two different focal region in the sample.

It should clearly indicate that this exemplary embodiment of the present invention may be applied or performed without the need to provide signs of completely dry connection. In other words, the creation of multifocality device may also be used in combination with a non-solid binder.

Accordingly, the third aspect of the present invention is directed to the formation of two different focal regions in the sample. In an exemplary embodiment, the implementation of the third aspect of this invention presents a device for irradiating the sample with focused acoustic energy to treat the sample containing the device, the cartridge and the source for the generation of sound energy. The cartridge has a chamber for receiving the sample. The device and the cartridge are adapted for insertion of the cartridge into the device. The cartridge and the instrument are separable�. The device is designed for the formation of at least two different focal regions of sound energy in the sample.

In addition, an exemplary embodiment of the third aspect of the present invention also relates to a corresponding device for irradiating the sample with focused acoustic energy to treat the sample, the device comprises a source for generating acoustic energy. The device is adapted to receive the cartridge which is separable from the device and provides a chamber for receiving the sample. The tool was developed for the formation of at least two different focal regions of sound energy in the sample, when the cartridge is inserted into the instrument.

Accordingly, in another exemplary embodiment of the provided cartridge, the cartridge unit for irradiating the sample with focused acoustic energy generated by the source to process a sample, comprises a chamber for receiving the sample. The cartridge is adapted for insertion into the device and is separable from the device. The cartridge is designed to provide educational opportunities to at least two different focal regions of sound energy in the sample when it is inserted into the device.

Moreover, it should be clear to indicate that the appropriate form of education for at least two RA�different focal regions in the sample through the device and a corresponding computer program element for controlling the device, forming multifocality in relation to the specimen contained within this variant implementation. Thus, the computer program element may differ in that it is adapted, when used in the device, to create multifocality relative to the sample to cause the executing device of the steps of the method.

In other words, given a Protocol processing with the use of the two focal zones for different conditions of focus. For example, the conditions of focus to perform mixing by circulation of fluid through the focused acoustic energy may differ from the requirements to perform lysis, for example, microorganisms. This variant implementation of the present invention meets these requirements.

By providing at least two different focal regions in the sample, the device can ensure the implementation of molecular diagnostic tests simple and inexpensive manner. In addition, this exemplary embodiment of this invention it is possible to avoid complicated locations piezometric, complicated systems and/or actuators. In addition, the result of the integration of several different functional capabilities (such as, for example, mixing, circulation and lysis) inside one chamber, vol�Lauda through two different focal regions, possible miniaturization of the device for molecular diagnostics.

In other words, the device for molecular diagnostics is a device with HiFu for multifocal molecular diagnostics for use in different focal areas to sample. This can be used for creating and combining various functional processing capabilities. For example, point focused HiFu may be optimal to perform lysis, and HiFu focused zone, may be optimal for mixing and/or circulation. Thus, the "point of focus" means a relatively small focal region, and the "zone focused way" means comparatively large focal region. Different focal regions may also differ in shape and size. These different focal meets the requirements of this exemplary embodiment of the present invention.

In addition, lysis by HiFu requires high sound pressures. High pressure is achieved through good quality focus, which is achieved in this exemplary embodiment of the present invention by initially well-focused part of the sound energy generated. In contrast to release of particles or cells from smears to high�obodai and homogenizing the sediment from the media for example, the strokes of the brush to homogenize the liquid present in the chamber, with reagents added in the camera, you may need mixing and circulation in a single chamber of the cartridge. Accordingly, the second part of the generated acoustic energy is focused in a relatively large, in the form of a zone of the second focal region in the sample. Accordingly, two different functional processing capabilities that can be applied to the sample at the same time, in a single camera and without any manual user intervention.

In accordance with another exemplary variant of implementation of the present invention at least two different focal field formed by a member selected from the group consisting of multiple sources, a single source and hybrid lens, a single source with zones of different roughness and single source excited in different ways at different positions of the source, and any combination of them. Such an element can be implemented in the form of an element that is external to the cartridge, or item related to the cartridge, or in the form of the item combined with the cartridge.

Multiple sources include at least two separate sources, as well as the matrix of sources, which is regulated electronically t�Kim, the superposition of the fields of all sources leads to the total field, having at least two focal region. In addition, a hybrid lens may be composed of material with an average degree of focus and of a material with a high degree of focus. These materials can be located in different parts of the lens, leading to multifocality. For example, curved hybrid lens may be mounted on a flat source, such as a Converter. However, it is also possible curved transducer with a curved hybrid lens, made of a material with a medium degree of focus and of a material with a high degree of focus. In order to find the optimized distribution of these two different materials can be accomplished acoustic modeling for different configurations. For example, the lens may be formed from polypropylene. In addition, the radius of the lens may vary depending on usage. To create multifocality on the receiving end, where the sample may also be a source with zones of different roughness, which means that the surface source has different values of surface roughness.

Different emitting areas, more specifically, the corresponding surfaces of these zones may have different parameters of surface roughn�Tosti. These different roughness parameters determine different characteristics of acoustic emission zones, which leads to at least two different focal zones. Thus, the source or the transmitter can choose to have these zones. However, on top of the Converter can be added an additional component, wherein this component corresponds to these different characteristics of surface roughness. In other words, the essence of this feature is that the surface of the transducer is segmented into smooth and rough zones, delivering, respectively, high and moderately focused acoustic energy, in particular HiFu, to sample.

It should be noted that the preferred embodiments of the other aspects of this invention should be considered as the preferred and disclosed variants of implementation in relation to this aspect and Vice versa.

In accordance with another exemplary variant of implementation of the present invention focused sound energy is used to reduce the viscosity of the sample.

It should clearly indicate that for this variant implementation of the present invention does not necessarily contain all the hallmarks of a dry connection. In particular, does not require a completely solid connector or completely dry pathway.

Accordingly, a fourth aspect of the present invention is directed to the application of focused energy to reduce the viscosity of the sample. In an exemplary embodiment, the implementation of the fourth aspect of this invention presents a device for irradiating the sample with focused acoustic energy to treat the sample containing the device, the cartridge and the source for the generation of sound energy. The cartridge has a chamber for receiving the sample. The device and the cartridge are adapted for insertion of the cartridge into the device. The cartridge and the instrument are separable. The device was designed to apply focused acoustic energy to reduce the viscosity of the sample.

In addition to this exemplary variant of implementation of the fourth aspect of the present invention also relates to a corresponding device for irradiating the sample with focused acoustic energy to treat the sample, the device comprises a source for generating acoustic energy. The device is adapted to receive the cartridge which is separable from the device and provides a chamber for receiving the sample. The device is designed to apply focused acoustic energy to reduce the viscosity of the sample, when the cartridge is inserted into the instrument.

Accordingly, in another exemplary embodiment of the provided with a cartridge box to�rtridge for device for irradiating the sample with focused acoustic energy generated by the source to process a sample, comprises a chamber for receiving the sample. The cartridge is adapted for insertion into the device and is separable from the device. The cartridge is designed to provide the capability of reducing the viscosity of the sample by means of focused acoustic energy applied to the sample when it is inserted into the device.

In addition to this exemplary variant of implementation contains the corresponding method of reducing the viscosity of the sample, preferably by means of such a device and a corresponding computer program element. Accordingly, a computer program element is characterized in that it is adapted, when used in the device, to reduce the viscosity of the sample by irradiating the sample with focused acoustic energy to cause the execution unit stages corresponding method.

In order to reduce the viscosity of a sample, such as, for example, the sample from bronchoalveolar lavage (BAL), saliva, blood, feces, or any other sample that is present on the smear, this variant implementation of the present invention provides the use of focused acoustic energy, for example, HiFu to cause this decrease. This method can be applied in the form of a complete solution "sample - in, result out", in which p�following pretreatment and lysis of the sample can be possible in one chamber of the cartridge. Accordingly, by only one single source is possible to perform full process of reducing the viscosity, further pretreatment and lysis.

For example, to reduce the viscosity of the sample can be used a source that has the following characteristics. Converter 3.0 MHz with a diameter of 25 mm and a focal length of 22 mm. in addition, the bottom of the cartridge may be located at a distance of 15 mm from the transducer. The approximate capacity of 5 watts can be applied to the sample for about 300 C. By application of HiFu sample may be more homogeneous after the HiFu exposure, and the viscosity may be reduced from the initial viscosity, e.g., viscosity, like water. Accordingly, it can be concluded that the force used by the HiFu combine the ability to reduce the molecular weight of macromolecules and, as a result, the viscosity and the ability to the circulation and mixing of the sample in the chamber.

It should clearly indicate that this exemplary embodiment of the present invention may be used for any application requiring circulation and/or mixing in THz range of volume in the device. Applications can also be used in biomedical Sciences, General microen�iza (microTAS) or labs-on-chip (lab-on-a-chip).

It should be noted that the preferred embodiments of the other aspects of this invention should be considered as the preferred and disclosed variants of implementation in relation to this aspect and Vice versa.

In accordance with another exemplary variant of implementation of the present invention further contains a detection unit for measurement on the sample. In this regard, the irradiation of a sample with focused acoustic energy causes the processing of the sample.

In other words, this exemplary embodiment of the present invention provides a complete system "sample - in, result out", which eliminated manual steps that must be performed by a user. The sample can be introduced into the apparatus and by means of focused acoustic energy of this sample is processed in the desired manner. Then or also a preliminary performance measurement can be applied to the specimen via the detection unit. Accordingly, the device can deliver the measurement results, for example, through the user interface to the user. For example, functionality such as dilution, mixing, mixing, circulation, pretreatment, incubation and lysis can be performed before or after any of izmereniyam detection by focused sound energy. Thus, the user is provided with a fully automated system.

It should also be noted that this exemplary embodiment of the present invention is not required to contain all the hallmarks of a dry connection. In particular, does not require a completely solid and dry the connector or completely dry way of distribution.

Accordingly, a fifth aspect of the present invention is directed to a detection unit for measurement on the sample. In an exemplary embodiment of the fifth aspect of this invention presents a device for irradiating the sample with focused acoustic energy to treat the sample containing the device, the cartridge and the source for the generation of sound energy. The cartridge has a chamber for receiving the sample. The device and the cartridge are adapted for insertion of the cartridge into the device. The cartridge and the instrument are separable. The device comprises a detection unit for measurement on the sample.

In addition, this exemplary embodiment of the invention also relates to a corresponding device for irradiating the sample with focused acoustic energy to treat the sample, the device comprises a source for generating acoustic energy. The device is adapted to receive the cartridge which is separable from the device and before�provide a chamber for receiving the sample. The device comprises a detection unit for measurement on the sample, when the cartridge is inserted into the instrument.

Accordingly, in another exemplary embodiment of the claimed cartridge, the cartridge unit for irradiating the sample with focused acoustic energy generated by the source to process a sample, comprises a chamber for receiving the sample. The cartridge is adapted for insertion into the device and is separable from the device. The cartridge is designed so that when it is inserted into the device, a detection unit may perform measurements on the sample.

In addition, it should be noted that this exemplary variant of implementation contains the corresponding method of measurement on the sample by means of such a device and a corresponding computer program element. Accordingly, a computer program element is characterized in that it is adapted, when used in such a system, "sample - in, result out", to trigger the device the steps of the method.

It provides sample processing in vitro by, for example, HiFu and simultaneously detecting in vitro, which leads to a complete system "sample - in, result out".

Especially for molecular device, which device in accordance with an embodiment is�the implementation of the present invention and providing the possibility of extraction, cleaning, amplificatoare and detection of nucleic acids should include the following information. Extraction and/or purification of nucleic acids based on adsorption and/or desorption on solid surfaces. Any surface, providing a sufficient capture area should be considered as part of the embodiment of this invention. Normal variants of implementation of the grips are (e.g., magnetic) particles and membranes. Any gripping material, capable of delivering nucleic acids of sufficient quality for the purposes of reproduction, should be addressed as part of the embodiment of this invention. Widely used materials are, for example, silica, magnetized silica, iron oxide, polystyrene, functionalized amino group. There might also be other materials.

The choice of the detection unit and, accordingly, the detection method may depend on the area of application, such as, for example, detection of nucleic acids, proteins or cells.

For amplificatoare and detection of nucleic acids, for example, describes a lot of isothermal methods and methods with thermal Cycling. One of the most used methods is the polymerase chain reaction (PCR). System "sample - in, result out" � according to this exemplary variant of implementation of the present invention performs the functionality PCR in the cell, in which the sample is also treated by HiFu.

PCR is further divided into two subcategories, namely, with the detection by end-point PCR and real-time rtPCR). Of these two categories rtPCR is used most widely (amplificatoare rtPCR proceeds simultaneously with the detection). For the detection of nucleic acids can be, for example, applied detectable markers such as fluorescent markers that can be incorporated into amplified nucleic acids during PCR. Can also be used other detectable labels or even the ways without the use of labels.

For detection of the protein can be used conventional approaches, such as the combination of capture antibody and optical reading, for example, fluorescent, or magnetic reading.

For the detection of cells can be used optical methods because they are widely used for counting, analysis of cell shape, etc., however, (di)electrophoresis and electrical properties can also be used for detection/characterization of cells.

All the above-mentioned detection of this variant implementation of the present invention correspond to the detection unit, which is used in this embodiment of the present invention. Accordingly, actual�private system "sample input the output can include any of these signs of detection or measurement.

In accordance with another exemplary variant of implementation of the present invention, the detection unit is designed to be applied to the sample at least one measure selected from the group consisting of optical measurements, magnetic measurements, thermal measurements, electrical measurements, chemical measurements, sound measurements, and any combination thereof.

The device may also include at least one of the following blocks: an extraction unit; a unit amplificatoare nucleic acid; a storage unit of the reagent; a detection unit for measurement on the sample, wherein the detection unit is designed to be applied to the sample at least one measure selected from the group consisting of optical measurements, magnetic measurements, thermal measurements, electrical measurements, chemical measurements, sound measurements and any combination of them. Under this option the implementation of this equipment may contain, for example: extraction unit; an extraction unit and the unit amplificatoare nucleic acids; extraction unit, the unit amplificatoare nucleic acid and a detection unit. In each of these options the storage unit of the reagent may be provided in addition to the elements�am every option listed in the preceding sentence. An extraction unit provides the possibility of obtaining nucleic acid from the sample that are processed by this equipment. Block amplificatoare nucleic acid provides the possibility of obtaining nucleic acid from a sample subjected to amplificatoare (when using, for example, PCR). The storage unit of the reagent includes a reagent required, for example, for extraction and/or amplificatoare.

In order to have a wide range of measurement capabilities, different types of sensors and detectors can be installed inside the unit. In addition, it may be favorable Association existing ultrasonic means for activation or sample processing with the possibility of conducting sound measurements. The detection unit may also be part of the cartridge. In other words, optical reading, however, it is also possible techniques using other tags to detect, for example, magnetic, electrical, electromagnetic, especially radio, as well as the methods without the use of labels.

In accordance with another exemplary variant of implementation of the present invention the device also includes a processor for coordinating the Protocol processing, the processor for data processing, display and user int�has.

It should be noted that the preferred embodiments of the other aspects of this invention should be considered as the preferred and disclosed variants of implementation in relation to this aspect and Vice versa.

In accordance with another exemplary variant of implementation of the present invention fully solid coupler is made of a material based on polymer; and wherein the material on the base polymer has a glass transition temperature Tgselected from the group comprising: Tg≥-30°C; Tg≥-10°C, Tg≥-5°C; Tg≥20°C; Tg≥40°C; Tg≥60°C; Tg≥80°C; Tg≥100°C; Tg≥120°C; Tg≥130°C; Tg≥140°C; Tg≥150°C and Tg≥160°C.

It should be noted that the importance of the glass transition temperature of the material is completely solid connector becomes more important, the higher the intensity of HIFU. For low intensity, for example, when the input power P of the Converter is less than 3 W, the value of Tgmay not be so important. This can be seen in Fig.22. The average intensity P, which, for example, between 3 and 6 watts, itself increases the attenuation, as described above, and then is able to play a more significant role, which may require the use of a polymer with a significantly higher Tg. At high intensities, above, for example, 6 W, important�ü selection of the polymer, based on the extent of his Tgbecomes even more significant.

It may be necessary to use with high intensity HiFu at room temperature the value of Tgwas above room temperature (about 50°C).

It was found that materials with a relatively high glass transition temperature Tgsupport, as opposed to materials with lower Tgduring functioning of the device and, accordingly, during the transfer of sound energy to their features of low attenuation. Accordingly, the use of these materials with low attenuation and high Tgas a fully solid coupler makes possible a very efficient transmission of ultrasound energy, which is important, for example, for sample processing, for example, for cell lysis. Especially for applications of HIFU, as described above, it is a useful effect realized by this invention. In other words, through the use of these materials may have reduced the power provided by the source, to realize a certain power of the HIFU focal region. Accordingly, the processing and/or functionality pre-processing can be realized with a reduced amount of power. This can save Energiya costs. In other words, the self-reinforcing effect of attenuation in the material for communication can be avoided by this invention. The attenuation per meter propagation paths can thus be reduced.

In order to provide a better understanding of this exemplary embodiment of this invention, should be taken note of the following physical processes:

The attenuation characteristic that the temperature of the material of the connector may begin to increase. In addition, it may also increase the attenuation of sound energy. This exemplary variant of implementation of the present invention now provides for the materials the advantage that they support relatively low attenuation, even if the temperature begins to increase during, for example, functioning with HIFU in the megahertz region.

Examples of such materials can be polypropylene with Tgapproximately -18°C, epoxy resin with Tgabout 60°C and silicones with Tgabout 60°C, about 100°C and about 125°C.

It should be noted that a sufficiently high glass transition temperature is associated with attenuation in the beginning of the test, the ultrasound intensity, thermal conductivity of the structure (the transfer of heat generated) and the time of exposure.

In other words, the choice of polymer with Oprah�specific value of T gdepends on several parameters, such as attenuation of the polymer at the beginning of the transmission of HIFU using the polymer as a solid connector and, therefore, before any absorption or the beginning of heat generation. In addition, we use the intensity or power of the spring is determined by the choice of polymer. In addition, thermal conductivity of the environment of the connector is a parameter that affects the choice of the polymer with a sufficiently high value of Tg. The high thermal conductivity of the system around the connector results in slower temperature rise and a lower maximum temperature, if the HiFu exposure is long enough to reach equilibrium.

In particular, this can be especially important when applying a relatively high intensity ultrasound. For example, when lysis is performed with the application of HIFU energy inside the sample, the required power can be relatively high. Accordingly, the methods of lysis with the use of HIFU according to this exemplary variant of the implementation can be quite beneficial.

In other words, a completely solid connector that is present on the path of propagation between the source and the destination, which is the cartridge that has a reduced attenuation of sound energy. In supplementary�lanie to this adjusted or selected acoustic resistance materials, transmitting the sound energy can be used to minimize the reflection losses at passage of boundary materials.

Accordingly, this device provides for completely dry connection, the following possible advantages: ease of use for the operator and reducing the execution time of the test, and, consequently, may be provided for other uses performed by less qualified personnel.

Polymers are particularly attractive class of materials for use as connectors, as in this case, are available in a wide variety of materials, freedom of choice designs in terms of shapes and sizes, the ease of duplication and the relatively low associated costs. This is further described in detail with reference to Fig.21-23.

In accordance with another exemplary variant of implementation of the present invention, in which the material based on polymer hardens during the curing temperature Tcselected from the group comprising: Tc≥20°C; Tc≥40°C; Tc≥60°C; Tc≥70°C; Tc≥80°C; Tc≥90°C; Tc≥100°C; Tc≥110°C; Tc≥120°C; Tc≥130°C; Tc≥140°C; Tc≥150°C; Tc≥160°C; Tc≥170°C and Tc≥180°C.

Attenuation in a fully solid coupler can be further reduced by about�their equal, when the curing temperature of the material based on the polymer during manufacture of the polymer increased. This is further described in detail with reference to Fig.21-23.

It has been found that during manufacture of the polymer, which includes the process step of curing, the curing temperature during the manufacturing stage of curing at least partially defines the glass transition temperature of the polymer material. As described above, a sufficiently high value of Tghas certain advantages when used in a molecular device with HIFU. Accordingly, by setting a certain value of the temperature of curing can be implemented with the desired value of Tgfor the polymer. This process step may be part of a method in accordance with another exemplary variant of implementation of the present invention.

In accordance with another exemplary variant of implementation of the present invention provides a method of irradiating the sample with focused acoustic energy to treat the sample. Accordingly, the method comprises the following steps: providing a device, providing the cartridge, providing a completely solid connector, providing a source for generating acoustic energy and the insertion of the cartridge into the device. In addition to t�, the cartridge has a chamber for receiving samples, and by inserting the cartridge into the device creates fully dry connection for sound energy between the source and the cartridge. The cartridge and the instrument are separable.

In accordance with another variant implementation of the present invention presents a device for irradiating the sample with focused acoustic energy to treat the sample. The device comprises a source for generating acoustic energy, a completely solid connector, wherein the device is adapted to receive the cartridge containing the sample, and a completely solid connector provides fully dry connection of sound energy between the source and the cartridge, when the cartridge is inserted into the device;

wherein the cartridge and the instrument are separable, and the device and the cartridge form a device in accordance with one of the above variants of implementation.

This embodiment of the present invention may be used with sound HiFu energy to treat the sample by means of methods or features, such as mixing and/or lysis, in, for example, a single camera. In addition, the device may include a detector and an excitation source that can both be used to perform optical, electrical, magnetic and/or mechanical� measurements. In addition, the device may contain a lens.

In other words, dry the communication can be realized through a fully solid coupler that is part of the device. Before the presence of the cartridge is implemented completely dry the path of propagation from the source through a fully solid coupler. By inserting the cartridge into the device full dry path of propagation between the source and the sample ends, and sound energy can be transmitted to the sample in order to process the sample.

In accordance with another variant implementation of the present invention presents a cartridge unit for irradiating the sample with focused acoustic energy to treat the sample, the cartridge comprises a chamber for receiving the sample, a completely solid connector, wherein the cartridge is adapted for insertion into the device. In addition, a completely solid connector provides fully dry connection of sound energy between the source and the cartridge, when the cartridge is inserted into the device, wherein the cartridge and the instrument are separable, and wherein the device and the cartridge form a device in accordance with one of the described variants of implementation.

Completely solid state, the connector may be permanently fixed to the cartridge. However, there are other possible re�message. The source may be, for example, a part of the device. By inserting the cartridge into the device is completely solid-state propagation path between the source and the sample.

In addition, the source may be contained in the cartridge. Accordingly, by inserting the cartridge into the device electrical leads from the device are in contact with the source, to provide a source of electrical energy.

For two of the above options implementation should be a clear way to indicate that a completely solid connector is located on the device or on the cartridge so that a completely solid connector must not form the full path of propagation itself, and may include other additional elements, dry connection. However, if it is desirable, in an exemplary embodiment of the present invention this can be implemented.

It should also be noted that part of the device may be a computing unit. This may be a separate unit in connection with the device, or computing tasks can be distributed between the computer unit and the device.

It should also be noted that all elements of the computer program mentioned above as exemplary embodiments of this invention, should be maintained � computing unit, which can also be a part of an embodiment of this invention. This computing unit may be adapted to perform or induce the execution of the method steps described above. In addition, it can be adapted to control the above components of the device. The computing unit may be adapted for controlling an automatic manner and/or to execute user commands. In addition, the computing unit may require the user to process the input data from the user.

Implementation options related to the elements of a computer program that includes computer program that fits from the start of application of the computer program element and a computer program that by updating converts an existing program into a program that uses this invention.

In accordance with another variant implementation of the present invention presents a machine-readable medium, machine-readable medium has stored on it a computer program element, computer program element is described in the previous or subsequent sections.

As the essence of this invention can be considered that the consumable cartridge, which the Department�imym from the device, forms a pathway with a fully dry connection for a focused sound energy when the cartridge is inserted into the device. Accordingly, the dry connection passes from the source of the generated acoustic energy to the sample.

It should be noted that some embodiments of the present invention are described with reference to the various objects of the invention. In particular, some variants of the implementation described with reference to the methods, while other variants of the implementation described with reference to the device. However, the specialist in the art will make the conclusion from the above and the following description that, unless specified otherwise in addition to any combination or signs relating to one of the objects of the invention, also any combination of features related to different objects of the invention, is considered within this application.

The aspects described above and other aspects, features and advantages of this invention can also be installed from the examples of embodiments that are described later in this document and are explained with reference to examples of embodiments. The present invention will be described in more detail later in this document with reference to examples of embodiments, which, one�co the present invention is not limited.

BRIEF description of the DRAWINGS

Fig.1 is a schematic view of a device for irradiating the sample with focused acoustic energy to treat the sample in accordance with an example embodiment of this invention.

Fig.2 - schematic representation of the cartridge having an acoustic window, in accordance with an example embodiment of this invention.

Fig.3 is a schematic representation of a cartridge in accordance with an example embodiment of this invention.

Fig.4-8 - schematic drawing of the source device in accordance with an example embodiment of this invention.

Fig.9 - schematic illustration of several components of the device in accordance with an example embodiment of this invention.

Fig.10-14 - examples of possible configurations of the device in accordance with an exemplary variant of implementation of the present invention.

Fig.15 - schematic representation of the electronic components used for the device in accordance with an example embodiment of this invention.

Fig.16 - the Protocol processing performed by the device in accordance with an example embodiment of this invention.

Fig.17-19 - schematic drawing of the device, creating�is Central to multifocality in relation to the sample, in accordance with an example embodiment of this invention.

Fig.20 is a block diagram representing a method in accordance with an example embodiment of this invention.

Fig.21 is a schematic view of a device for irradiating the sample with focused acoustic energy to treat the sample in accordance with an example embodiment of this invention.

Fig.22 and 23 are graphs of the results obtained using the device for irradiating the sample with focused acoustic energy to treat the sample, in accordance with an example embodiment of this invention.

DETAILED DESCRIPTION of embodiments of

Similar or related components on multiple figures are presented under the same numeric designations. Views of the figure is schematic and not fully scaled.

Fig.1 shows a device 100 for irradiation of the sample 101 of focused acoustic energy to treat the sample in accordance with an example embodiment of this invention. It is clear that the device has several components that constitute the device 102, the cartridge 103 and the source 105 (shown only in dashed lines) for the generation of sound energy. In addition, a schematic view of the propagation path 106(dash-dotted line) of sound energy, starting from the source 105 and ending at the sample 101. Accordingly, the cartridge has a chamber 110 for receiving the sample 101. Shown inside of the device 102 provided by a fully solid coupler (not shown) 104 in order to form a path of propagation without liquid substance. Thus, the source 105 and a fully solid coupler 104 are located inside the device 102 and, accordingly, may not be visible directly. In addition, the device 102 and the cartridge 103 is adapted for insertion of the cartridge into the device, wherein the cartridge and the instrument are separable. It should be noted that the hidden components, such as source, a lens, a fully solid coupler and the acoustic window can be seen in the subsequent Fig.9, showing an exploded view, and Fig.2, respectively.

In addition, inside the cartridge shown a detection unit 111, for example, a sensor designed to perform measurements on the sample after or before a possible treatment focused sound energy. Also shows the processor 112 for coordinating the Protocol processing associated with the detection unit 111 and which is also connected to the display processor 114 and 113 to process the data. The processor 112 to coordinate treatment Protocol is connected to the device 100 and is also connected with the block�Ohm detection 111. Accordingly, the processor 112 has the option of regulating this system "sample - in, result out", in which fully automated processing of the sample by means of focused acoustic energy, in particular by means of HiFu can be combined with analysis and measurements, such as, for example, optical measurements, magnetic measurements, thermal measurements, electrical measurements, chemical measurements, sound measurements, and combinations thereof.

Due to the use of HiFu and the corresponding short wavelength (compared to, for example, with the known types of ultrasound application, operating in the range of 20 kHz - 100 kHz) the dimensions of the focal region can be reduced, and, accordingly, possible miniaturization of molecular devices in General. This is an extremely important advantage of the presented embodiment of this invention, for example, with regard to the requirements of the hospital or lab to have real small-sized system due to the very limited space available in these environments. In addition, the combination of the functionality of the processing, pre-processing, lysis and prior or subsequent measurements can reduce the cost and time of this treatment, the sample or molecular� diagnosis.

In addition, it may be possible to provide such as device 100 with multifocal structure. Accordingly, the device forms at least two different focal region in the sample 101. This can be done by at least two different sources, a single source and hybrid lenses or sole source areas with different roughness. Moreover, there is also a combination of these possibilities.

In addition, the device 101 can be used to reduce the viscosity of the sample by means of focused acoustic energy, particularly through application of HiFu.

In addition, the device makes it possible to combine in a single camera 110 pre-treatment and/or incubation and/or lysis by focused sound energy coming from one single source 105. In particular, application of HiFu. Accordingly, pretreatment and lysis may include various functionalities that were described in previous sections. This can reduce the cost and time of this treatment, the sample or molecular diagnostics, and can also be reduced by the space occupied by the device due to combining both functionality inside a single camera. In addition to t�, can be reduced the technical complexity of the device.

Method pre-treatment or method of lysis can be carried out or performed by means of focused acoustic energy, in particular by means of HiFu, and, respectively, by means of a source of sound energy or Converter that generates a plot of HiFu exposure at the location of the sample, providing pre-processing and/or lysis of the sample. However, also other devices, which can be combined with a device for molecular diagnostics and that are necessary for performing the method, can create a desirable method. For example, an additional device for heating device for cooling or block addition of a reagent (dispenser) with feed lines can be combined with a device for molecular diagnostics to provide additional incubation with the reagent at elevated temperature.

The reagent may be, for example, lysozyme, which can be initially mixed and then incubated at 37°C. In particular, mixing, circulation, liquefaction and homogenization can be performed by irradiating the sample HiFu.

In addition, the lysis of microorganisms, such as, for example, gram-negative and gram-positive bacteria, mold and yeast, can be performed through�Twomey HiFu using the device 100, shown in Fig.1. Lysis may also include incubation of the sample with the reagent at room temperature or elevated temperature. Reagents can be, for example, GuHCl/prot K, which is initially mixed and then incubated at about 56°C and optionally cooled to ambient temperature, or GuSCN, which is initially mixed and then incubated at about 70°C and optionally cooled to about 25°C.

Optionally, the camera has a filter at its outlet, or filter to its output channel to prevent movement of residues in the extraction of the cartridge.

Fig.2 shows the acoustic window 107 of the cartridge 103, wherein the acoustic window is made of a flexible material, which is shown as a plastic film 108. You can see that round acoustic window 107, which is shown in the bottom view, covered with plastic film 108, which is an interface environment that can adapt to the shape of, first, the cartridge 103 and, secondly, a completely solid connector, or the source may be brought into contact with the plastic wrap directly on the surface 108. Position 115 shown the lower part of the cartridge, which is fixed to a flexible film, for example, laser welding.

Fig.3 shows the cartridge 103 with the chamber 110 in its normal�Noah or operating position, which represents a rotation by 180° compared to Fig.2. In other words, Fig.2 shows the bottom part 115 of the cartridge with its lower side, and Fig.3 shows the cartridge with the bottom part 115 with its upper side. Shows the cartridge and the locking mechanism of the film can then be together as one node is inserted in the device 100 shown in Fig.1 and can be pressed on top of the device 102. This procedure inserts will form a pathway for the transmission of sound energy from the source 105 (shown in dash-dotted lines) in Fig.1 to the sample 101 in Fig.1.

Fig.4 shows an example of a possible source used in the device in accordance with an exemplary variant of implementation, which shows the source 105 and the connector 104, in this example shown here is a polymeric connector.

Fig.5 shows another example of a source that generates the focused acoustic energy, in particular HiFu, the source 105 may be a piezoelectric transducer, and a metal lens 109 is fixed on top of this, for example, flat Converter. In addition, the connector 104, for example, polymeric connector.

In contrast, Fig.6 shows the configuration of a polymer coupler in which the curved source 105 is combined with a polymeric connector 104. In addition � this for example, the lens may be located on top of the polymeric connector and is supplied by others, for example, polymer, connector on top of the lens to provide an efficient dry connection towards the cartridge.

Fig.7 shows the piezoelectric configuration where you can see a flat piezoelectric transducer, operating as a source 105 natural focus. In addition, applied a very thin layer of polymer to modify the surface roughness, in order to facilitate effective dry connection. In addition, it also shows electrical leads.

Fig.8 shows another possible configuration of the components of the source in which metal lens 109 is in direct contact with a flat transmitter operating as the source 105. As will be seen in Fig.10-14, any combination of these configurations, which leads to a wide range of applications.

Fig.9 shows an exploded view of the device 102, containing the heat sink 900, different ring 901 of the housing, partially creating the case for a fully solid coupler 104, which may be, for example, a material based on polymer gel or solid, an additional ring 902. In addition, the source 105 is shown as a piezoelectric transducer. In addition to et�mu completely solid state, the connector 104 is indicated by dash-dotted lines. These elements can be part of the device 102, and they can form a receiving component, which by means of the insertion of the cartridge on top of the retainer 903 foil creates a pathway that consists only of substance, not a liquid. Elements 901, 902 and 903 are also a part of the body of the connector. The case is made so that the height of the connector can be changed by selecting the number of rings 901 of the housing. The latch film 903 is fixed to the film (not depicted) that is used to cover the connector.

Fig.10 shows an overview of the combinations of possibilities to create a dry connection. Accordingly, the first line provides information about the structure of the cartridge 103, the second line provides information about the structure of the connector 104, the third line provides information about the structure of the lens 109 and the fourth line provides information about the structure of the source or Converter 105. It can be seen that five different configurations are shown as examples. 1001 shows the connector configuration on the basis of solid gel, 1002 shows the configuration of a polymer connector with metal lens 1003 and describes the configuration of polymeric connector. 1004 describes a solution for dry connection, which uses only the piezoelectric configuration (piezoelectricity� material has a thin layer of polymer, to modify the roughness of the surface of the transducer), and 1005 describes how can be installed configuration with a metal lens to provide a dry contact. 1001 indicates that the source may be shaped like a lens and, accordingly, to determine the generation and focusing of sound energy. In addition, shown in column 1002, the lens can be physically combined, for example, can be glued together with solid connector 104. In addition, a completely solid connector 104 can be attached directly to the source 105, as shown in column 1003. However, there is also direct contact between the cartridge and a piezoelectric source, as shown in column 1004. In addition to this configuration, with a metal lens describes that the source 105 of the curved shape can be fixed concavo-concave lens, for example, a metal lens.

Other structural features may be shown in the detailed reviews of 1100 in Fig.11, 12, 13 and 14. These reviews are more detailed than in Fig.10, as introduced, two additional rows to distinguish whether a component part of the cartridge, a part of the source (meaning that it is part of the device) or physically separated component.

It should clearly wook�AMB, that any component is shown and described may be part of a Converter, cartridge, or may be physically separated component. In addition, any combination of components may be used to separate the different functionalities. For example, a thin film having a high flexibility, can be used to tailor the shape of the transducer. In combination with a fully solid coupler having less flexibility, but lower attenuation than the film, this corresponds to the splitting functionality in relation to the attenuation and flexibility. This can lead to a favorable combination of different components to ensure effective dry connection.

The string 1101 describes whether there is a structure in which a fully solid coupler is part of the cartridge. In contrast, line 1102 describes the fact that a fully solid coupler is part of the source and, accordingly, a part of the device. Also both possibilities can be realized for the device at the same time. Similarly, the third possibility 1104 describes what a fully solid coupler is physically separated component entered on the path of propagation. Again, you can see that may be provided combinations and source 1103. As can be seen in Fig.11-14, possible a wide range of structural possibilities for dry communication device using, for example, HiFu.

Fig.15 shows an exemplary 1500 electronic components used to generate a focused sound energy. Correspondingly, function generator, power amplifier, oscilloscope, and an ultrasonic transducer connected together in order to create an acoustic field. After focusing the emitted sound energy she faces the sample and causes various akusticheskii or akustisches reaction. This is a sample processing caused by the device. In other words, Fig.15 shows the configuration of a laboratory structure for ensuring and research established functional characteristics. Industrial device may not turn on the oscilloscope and function generator and an amplifier can be included in specific and manufactured for a specific purpose electronic equipment.

Fig.16 shows a possible treatment Protocol for the application of pretreatment and lysis in a single chamber by means of only one single source. The Protocol processing 1600 has several stages, for example, the Protocol begins with pre-processing 1603 of the sample by means of HiFu, �ATEM is applied to the sample mixing 1604, then the possible incubation 1605 with different substances. Possible additional stages of mixing and incubation. These different functionalities, created or caused by the sound energy due to akusticheskii or akustisches interactions, are all part of pre-processing 1601. Then the possible lysis 1602 inside the same the only camera that can be caused by the same single source that was used to perform pre-processing. As possible steps that can be mentioned mixing and incubation. However, there may also be special lysis 1606 by HiFu, and additional phases 1607 filtering. Accordingly, the designation 1608 describes any sample with the target material to be detected, for example, faeces, blood, urine, saliva, specimen from bronchoalveolar lavage (BAL), cerebrospinal fluid (CSF), the sample swab or brush. In addition, the reagent for the first pre-processing (e.g., chemical(s) compound(I) and/or enzyme(s)) shown in the designation as 1609. The second reagent for pretreatment (chemical(s) compound(I) and/or enzyme(s) as shown 1610 and 1611 is a third reagent for pretreatment (chemical(s) compound(I) and/or enzyme(s)). The first Rea�UNT for lysis (chemical(s) compound(I) and/or enzyme(s)) is marked as 1612. 1613 shows a reagent for the extraction, for example, to bind DNA to the silica. Presents the figure is merely exemplary variant of implementation and the filter should not be placed inside the chamber for lysis.

Fig.17 shows multifocal structure of the device 1700 in accordance with another exemplary variant of implementation of the present invention. It can be seen that the cartridge 103 having the chamber 110 with the sample 101, also features the ability to have a certain amount of air 1701 above the sample. In addition, two different source 105 is applied to this structure to form a first focal region 1702 and a second focal region 1703. In addition, the acoustic window of the cartridge should have a low attenuation and a minimum thickness to avoid heating up the material and provide a high intensity in the focal areas. For mass production the preferred polymer is capable of forming by injection molding. It may be preferable that there be no contact focal regions with the chamber walls. At high intensities it can lead to melting of the wall. Also it may be desirable to have a transducer with a large focal plane area 1702 was located opposite the air volume 1701. This leads to optimal mixing and circulation, and may reduce the risk of p�of Alenia the wall of the chamber.

Fig.18a-18b show that multifocality device operating, for example, in the range of HiFu can be created only by a single source. Respectively, of Fig.18a shows multifocal structure 1700 hybrid lens 1800, having a first emitting area 1801, the second radiating area 1802 and the third radiating area 1803. It is also possible that in the concentric structure of the first and third radiating area equal. You can also see that in the sample 101 is formed by three different focal areas 1804-1806. In the concentric structure is, accordingly, a case in which 1804 and 1806 describe the same focal region having an annular shape around the second focal region 1805.

You can see that the source 105 may be a flat shape, and a hybrid lens 1800 is attached to the source.

Fig.18b shows multifocal structure 1700, in which the hybrid lens 1800 has a shape that is adapted to the shape of a curved source 1500. Fig.18b hybrid lens has three emitting zones and three focal region formed of three radiating zones. Different emitting zone may consist of different materials focusing. For example, the outer material forming the zones 1801 and 1803 may be Srednekolymsk external material with internal material forming zone 1802 may be silnik�siraudin material. Segmented lens 1800, respectively, contains silviocesare material and srednevekovoi material. This may be a case shown in Fig.18b. These different focal region to provide the user the opportunity to implement different functionality, such as mixing and lysis, at the same time by using only one single source. This can reduce the execution time, for example, molecular tests and, in addition, can be reduced the costs and requirements of space because it requires only a single source. In addition, can be reduced technical problems and maintenance costs.

In this regard, the allocation of materials with different focus can be adapted to the desired processing, lysis or analysis. Accordingly, the distribution of material inside hybrid lenses or segmented lenses are not excluded by this exemplary variant of implementation of the present invention.

The following paragraph refers to modeling the combination comprising a flat transducer and a curved lens to confirm the concept of hybrid lenses. It is possible to layout may, for example, include a material with high acoustic impedance, such as, for example, aluminum, the material � low acoustic impedance, such as polypropylene, is used as the material of the lens, the radius of the lens and the inner diameter of the chamber is, for example, 8 mm, and polypropylene, taken as a chamber wall thickness of 0.5 mm, and the height of the liquid is 35 mm, the frequency for the simulation is 1 MHz and the set pressure of the piezoelectric transducer is 1000 PA. The simulation results showed that the maximum pressure along the Central axis of symmetry is maintained at a very constant high level during the transition from a material with high acoustic impedance (aluminum) to segments increased size of a material with low acoustic impedance, such as polypropylene. In other words, the pressure remains at a level high enough to ensure lysis. Secondly, the results showed that when the size of the polypropylene segment is large enough, the conditions of minimum and maximum pressure outside the Central axis of the chamber, providing mixing. Effective functioning of hybrid design hybrid design is achieved when a material with a high index (e.g., aluminum) usually takes anywhere from 1/5 to 1/2 of the entire lens when the material with the lowest index is plastic with low scattering. Accordingly, the hybrid lens is an opt�th generation multifocal sound energy, in particular, multifocal HiFu from a single piezoelectric element. This solution can be used for communication using HiFu dry boundary, and also for connection to a liquid or hydrogel and direct contact with the fluid.

Fig.19 shows multifocal structure 1700, in which the source 105 has areas with different surface roughness. 1903 shows a top view of the annular source 105 having a zone of 1904 with the first surface roughness and the area of 1905 with a second surface roughness that create multifocality. You can see that the first focal region of 1900 and the second focal region of 1901 differ from one another. In this third focal region 1902 is the same as that of the first focal region of 1900, as area 1905 with the second roughness is a circular surface, which leads to the formation of ring-shaped focal regions of 1900 and 1902 around the second focal region 1901. Due to different surface roughness creates a different relationship with the material, transferring the sound energy. Therefore, different roughness leads to the formation of different focal regions.

It should clearly indicate that multifocality due to the different roughness of the surfaces may not be used with signs su�Oh connection of this invention and can be applied directly to the device for irradiation of the sample multifocusing sound energy, to process the sample.

For example, in the range of 1 to 2 MHz, the effect may be moderate for the roughness of 10 μm and may be significantly higher for the roughness of 50-80 microns. Accordingly, the curved transducer with rough and smooth segments is optional to generate multifocal HiFu from a single piezoelectric element. Compared with other solutions with a lens or multiple sources, this variant of the implementation can be simpler.

Fig.20 shows a block diagram describing a method of irradiating the sample with focused acoustic energy to treat the sample, which includes the following steps: providing a device (S1), the provision of a cartridge (S2), providing a completely solid connector (S3), providing a source for generating acoustic energy (S4). Next is the introduction of the cartridge into the device (S5), wherein the cartridge has a chamber for receiving the sample and through the introduction of the cartridge into the device is provided completely dry connection of sound energy between the source and the cartridge. In addition, the cartridge and the instrument are separable.

Fig.21 shows a schematic representation of a device with a device comprising a transmitter 105, a fully solid coupler 104, the cartridge 103 having the chamber 110 for obrabativala, for example, HIFU through device 102. The bottom 2100 cartridge has an acoustic window made of film.

Fig.22 shows a graph 2200, which illustrates the advantages of a completely solid connector with a sufficiently high glass transition temperature Tg. From curves 2203-2207 graph it can be seen that a completely solid connector with an increased glass transition temperature Tgprovides less attenuation of ultrasonic energy within a completely solid connector. These results will be described in detail later in this document.

Abscissa 2201 displays the input power supplied to the source 105 (not shown) generating acoustic energy, for example, HIFU. The ordinate displays the so-called time constant clipping. It represents the time between switching on the power source, generating, for example, HiFu, and the complete disappearance of the fountain (cut). This formation of the fountain described above. It is created by HIFU waves and is used to reduce the threshold power at which the sample begins cavitation. The fountain consists of a material sample (e.g., fluid). Because education is such a fountain depends on the sound energy that is transmitted through a fully solid coupler to the sample, the disappearance of the fountain means less per�given sound energy. The results of the test using different materials with different glass transition temperatures is shown in Fig.22.

In other words, the time cut-off is taken as a measure for the development with time of the attenuation or absorption observed in the material is completely solid connector. The results for a range of materials and thicknesses shown in Fig.22 and 23.

Thus, Fig.22 shows the results for the connector 2203 silicone 601 3 mm thick, having a glass transition temperature of 60°C. 2204 depicts the results for a completely solid connector, made of epotek 301, 3 mm thick, having a glass transition temperature Tgabout 60°C. 2205 depicts the results for a connector made of silicone 601 with a thickness of 6 mm, having a glass transition temperature of 60°C. 2206 depicts the results for a completely solid connector with a thickness of 1 mm, made of polypropylene (PP) having a glass transition temperature Tgapproximately -18°C. 2207 depicts the results for a completely solid connector, made of epotek 301 with a thickness of 5 mm, having a glass transition temperature of about 60°C. All the samples have temperature curing 60°C, except for polypropylene (PP).

Fig.22 shows that the polypropylene (PP) is even at a moderate intensity pretty bad material. Attenuation as epoxide�th resin, and silicone increases, as expected, with the thickness of a completely solid connector. Attenuation for silicone lower than for epoxy resin. For all of these materials with high temperature Tgclipping occurs when continuous input power <6 mo. This capacity can be insufficient for processing the sample. Accordingly, for a wide range of processing device for molecular diagnostics the present invention provides polymers with a sufficiently high temperature Tg.

Additional experiments showed that, firstly, the observed phenomenon is not due to a change of the Converter over time. Second, this phenomenon may be reversible (if the material is not subjected to a "burn down" of intensities). After approximately 1 min, the material returns to its original state, and the experiment can be repeated. This observation suggests the dependence of material properties on temperature.

Fig.23 shows a graph 2300, which shows the effect of temperature curing material on the base polymer used as a solid connector. Abscissa 2301 displays the input power, and the ordinate 2302 displays a time to failure, i.e. the time constant clipping. 2303 at 2306 depict grap�completely solid state and different connectors. 2303 depicts the result for a completely solid connector with a curing temperature Tcconstituting 100°C, 2304 depicts the results for the connector with Tccomponent 125°C, 2305 depicts the results for the connector with Tcof 60°C, and 2306 also depicts the results for the connector with Tcof 60°C. in Other words, Fig.23 shows that the effect of attenuation also depends on the temperature of curing. With increasing temperature curing time constant clipping is substantially increased. An exemplary embodiment of the present invention utilizes this advantage. In other words, in General, a higher curing temperature Tcdirectly leads to increased glass transition temperature Tg.

Additional experiments with the material, cured at 60°C, showed that:

first, use the fountain, disappearing at a water temperature of 8°C or more. Secondly, when the fill factor of 20% the time constant of the cut-off is shifted to >120 seconds for peak power from 0 W to 65 W (average power of 13 watts). For a peak power of 90 W (average power 16 W) time constant cut-off was reduced to 10 seconds.

Example of possible equipment for these tests may include the following devices: PM5193: programmable� synthesizer/function generator 0.1 MHz-50 MHz, amplifier: power amplifier ENI 240L 50 dB 20 kHz-10 MHz or power amplifier AR Worldwide KAA204 50 dB RF of 0.5-100 MHz 200 watts, Tektronix TDS3014: four channel color digital phosphor oscilloscope; Agilent 4395A: 10 Hz-500 MHz/10 Hz-500 MHz/10 kHz-500 MHz network analyzer/spectrum/impedance and piezoelectric transducer HiFu: JR20/60 supplied by Dongfang Jinrong.

In the claims the word "contains" does not exclude other elements or steps, and the singular does not exclude the possibility that there is more than one such element. Notations shall not limit the scope of the claims.

A list of digital symbols

100 Device

101 Sample

102 Device

103 Cartridge

104 Fully solid-connector

105 Source

106 Pathway

107 Acoustic window

108 Flexible material

109 Lens

110 Camera

111 a detection Unit

112 the Processor to coordinate treatment Protocol

113 Processor for processing data

114 Display

115 lower part

900 Heatsink

901 Ring body

902 Additional ring

903 Retainer foil

1000 Review combinations of possibilities to create a dry connection

1001 connector Configuration on the basis of solid gel

1002 Configuration of polymeric connector with metal lens

1003 Configuration polymannuronides

1004 Only piezoelectric configuration (in this case the piezoelectric material is a thin layer of polymer to modify the surface roughness)

1005 Configuration with metal lens

1100 Detailed reviews of combinations of possibilities to create a dry connection

1101 a String describing that a fully solid coupler is part of the cartridge

1102 String describing that a fully solid coupler is part of the device

1103 Component that combines the functionality of the lens and the source (curved source)

1104 String describing that a fully solid coupler is physically separated component

1500 Electronic components used to generate a focused sound energy

1600 Possible treatment Protocol for the application of pre-processing, incubation and lysis in a single cell using a single source

1601 part of the pre-treatment Protocol

1602 part of the lysis Protocol

1603 Pre-HiFu treatment

1604 Mixing

1605 Incubation

1606 Lysis HiFu

1607 Filtering

1608 the Sample with the target material to be processed

1609 Reagent for the first pre-processing

1610 Reagent for the second pre-processing

111 the third Reagent for pretreatment

1612 the First reagent to lyse

1613 Reagent for extraction

1700 Multifocal structure

1701 Volume of air above the sample

1702 First focal region

1703 Second focal region

1800 Hybrid lens

1801 First radiating area hybrid lenses

1802 Second radiating area hybrid lenses

1803 Third radiating area hybrid lenses

1900 First focal region

1901 Second focal region

1902 Third focal region

1903 a top View of the source 105 with areas with different roughness

1904, the source Zone with the first roughness

1905 the source Zone with the second roughness

S1 Providing unit

S2 Provision cartridge

S3 the Provision of a fully solid-connector

S4 providing a source for generating sound energy

S5 Insert the cartridge into the device

1. The device (100) for irradiating the sample (101) of focused acoustic energy for treatment of a sample containing:
the device (102);
cartridge (103);
fully solid state connector (104);
source (105) for generating acoustic energy;
the cartridge has a chamber (110) for receiving a sample;
fully solid state connector provides fully dry connection of sound energy between the source and the cartridge;
the device and the cartridge are adapted for insertion Carter�JHA in the device;
the cartridge and the instrument are separable, and
focused sound energy is focused high intensity ultrasound (HiFu).

2. The device according to claim 1,
in which the device and the cartridge are arranged in combination such that by inserting the cartridge into the device is formed pathway (106) to transmit sound energy from the source to the sample; and
the pathway consists only of substance, not a liquid.

3. The device according to claim 1,
in which a completely solid connector contains a material selected from the group consisting of a solid gel, a rubber, an elastic film, a material based on polymer, thermoplastic polymers, the polymer having a low attenuation of sound vibrations, metal, semiconductor, ceramic, polypropylene, aluminum and multilayer packages of these materials.

4. The device according to claim 1,
wherein the cartridge contains an acoustic window (107);
an acoustic window made of flexible material (108);
completely solid state, the connector is physically in contact with the acoustic window by inserting the cartridge into the instrument.

5. The device according to claim 4,
which is completely solid state, the connector has a first contact surface for contacting the acoustic window (107);
the cartridge has a second contact surface DL� contact with the acoustic window; and
at least one surface of the first contact surface, the second contact surface and the acoustic window has a value of surface roughness selected from the group comprising a value less than 0.5 micrometers, less than 1 micrometer and less than 2 micrometer.

6. Device according to any one of claims.2-5,
in which the propagation path has a gradient of acoustic impedance; and
the gradient decreases monotonically in the direction from the source to the sample.

7. The device according to claim 1, further comprising:
the lens (109) for focusing the generated acoustic energy to the sample;
the lens is selected from the group consisting of a lens, which is a physically separate component placed between the source and the cartridge, a lens that is part of the source, the source with the focusing form, which is a lens, a matrix of sources that generate focused acoustic energy, a lens forming part of the cartridge, a lens constructed of polymer having low attenuation of sound vibrations, metal filter, ceramic filter, polypropylene lens, aluminum lens, hybrid lens, and any combination thereof.

8. The device according to claim 1,
in which one chamber of the cartridge pretreatment and lysis are applied to the sample through the focused sound �power;
pre-processing is a method selected from the group consisting of mixing with a reagent, circulation, release of cells, pathogenic microorganisms and the matrix material of the stroke, the release of cells, pathogenic microorganisms and the matrix material from the brush, liquefaction, incubation of the sample with the reagent at room temperature or elevated temperature, shaking, mixing, stirring, extraction, extraction of nucleic acid (NA), the generation of flow, homogenization of the sample, separation by centrifugation, and any combination thereof, and
in which lysis is a method selected from the group consisting of mixing with a reagent, circulation, lysis of microorganisms, incubation of the sample with the reagent at room or elevated temperature, and any combination thereof.

9. The device according to claim 1,
in which the device is adapted to form at least two different focal region in the sample.

10. The device according to claim 9,
wherein at least two different focal field formed by a member selected from the group consisting of multiple sources, a single source and hybrid lens, a single source with zones of different roughness, a single source, which is excited in different ways at different�Azaniah source and any combination of them.

11. The device according to claim 1, further comprising at least one of the following blocks: an extraction unit; a unit amplificatoare nucleic acid; a storage unit of the reagent; a detection unit (111) for performing measurements on the sample, wherein the detection unit is designed to be applied to the sample at least one measure selected from the group consisting of optical measurements, magnetic measurements, thermal measurements, electrical measurements, chemical measurements, sound measurements and any combination of them
in this case, the irradiation of a sample with focused acoustic energy causes the processing of the sample.

12. The device according to claim 3,
which is completely solid state, the connector is made of a material based on polymer; and
in which, the material on the base polymer has a glass transition temperature Tgselected from the group consisting of: Tg≥-30°C; Tg≥-10°C, Tg≥-5°C; Tg≥20°C; Tg≥40°C; Tg≥60°C; Tg≥80°C; Tg≥100°C; Tg≥120°C; Tg≥130°C; Tg≥140°C; Tg≥150°C and Tg≥160°C.

13. The device (102) for irradiating the sample (101) of focused acoustic energy for treatment of a sample containing:
source (105) for generating acoustic energy;
fully solid state connector (104);
the device is adapted for receiving a cartridge (103) containing clicks�sec and which is separable from the device; and
fully solid state connector provides fully dry connection of sound energy between the source and the cartridge, when the cartridge is inserted into the instrument.

14. The device according to claim 13, wherein the device has accepted the cartridge (103) containing a sample and which is separable from the device, and the device and the adopted form a cartridge device (100) according to any one of claims.1-12.

15. Cartridge (103) for the device (102) for irradiating the sample (101) of focused acoustic energy generated by source (105) for processing a sample, containing:
the chamber (110) for receiving a sample;
fully solid state connector (104);
wherein the cartridge is adapted for insertion into the device and is detachable from the device; and
fully solid state connector provides fully dry connection of sound energy between the source and the cartridge, when the cartridge is inserted into the instrument.

16. The cartridge of the device according to claim 15, wherein the cartridge is inserted into the device, and the device and inserted the cartridge form a device (100) according to any one of claims.1-12.

17. The method of irradiating the sample with focused acoustic energy for treatment of a sample, comprising the following stages:
the provision of the device (S1);
providing a cartridge (S2);
the provision of a fully solid state connector (S3);
providing a source for generating acoustic energy (S4);
insert cartridge Pribor (S5);
the cartridge has a chamber for receiving the sample;
when you insert the cartridge into the device to provide a fully dry connection of sound energy between the source and the cartridge; and
the cartridge and the instrument are separable.



 

Same patents:

FIELD: motors and pumps.

SUBSTANCE: simulation device contains an oil batcher, a dispersion chamber and a lubricant oil decomposition chamber (1). At the air outlet downstream the chamber the diffuser (2) is located. On the chamber the heater (3) with the thermocouple (4) and the thermorelay (5) is installed. The device includes the air duct (6) supplying the pumped-over hot air into the lubricant oil decomposition chamber connected through the manometer (7) to the air compressor (8). The device contains the cylinder (13) filled with ultra-pure nitrogen, (23, 24) the sealed gage tank with air cavity with oil and a cover for oil filling, with the oil pipeline connected to it through the gas pipeline with the regulator (12), the adapter (11) and cap nuts. The gage tank (9) is connected through the adapter (11) with cap nuts (20, 21) to the measured capillary (15) in a cooling jacket (16) with circulating water through the thermostat with the pump (18) and radiators, attached to the decomposition chamber by means of the cap nut (22) and the sealing cone (25). Also the device comprises the additional chamber (26) screwed to the main decomposition chamber of (1) coaxially and sealed with a gasket (27), with the rod with a flywheel (17) installed inside, with threaded and non-threaded parts. Meanwhile the threaded part is implemented with a possibility of movement in the internal washer with a thread (28) for adjustment of the decomposition chamber volume and change of conditions of simulation of oil concentration, while the non-threaded part is sealed in a gland with graphite seal (29).

EFFECT: improvement of accuracy of simulation of composition of oil decomposition products in aviation gas-turbine engines.

1 dwg

FIELD: aircraft engineering.

SUBSTANCE: invention relates to aircraft cabin air samplers, gadgets for analysis of admixtures in aircraft cabin air samples for analysis of concentration of contaminants in aircraft air conditioning systems and for determination of the composition of harmful admixtures and dangerous concentrations of gases and vapours in air. This sampler comprises evacuated vessel as air consumption booster, absorption cartridge with sorbent-concentrator composed of sharpened steel tube with plugs of glass wool at tube ends, with side bore in said tube filled with sorbent and glass wool. Evacuated vessel is composed of cylindrical case with inlet and outlet pipes fitted at case ends. Outlet pipe is provided with tube of vacuum rubber and metal plug to be fitted in the tube free end after evacuation. Inlet pipe is welded to the case end and features ID larger than that of the case inlet and internal thread. Aforesaid absorption cartridge with sorbent-concentrator is fitted in said inlet pipe and, partially, in evacuated vessel used also as a sampler of admixtures not absorbed by concentrator. Locking device composed of the tube with air sample passage inlet is screwed via seal ring in evacuated vessel surface neck to tight fit. Cover with stiffness ribs and rubber washer is secured to said locking device and aligned therewith. Lever with triangular cam at the end is articulated with the device on opposite side from the cover attachment side to lift said cover to unseal the system and to bleed air. Said lever and cover are secured to be revolved in one plane relative to axles of rotation and attachment. Springs secured from one side to locking device case and to cover stiffness ribs on opposite sides. This makes said cover opened and cover closed at lowered lever and cover located at lever can outer leg. Lever shifted, cover goes up to unseal the system and to bleed air.

EFFECT: higher sampler sensitivity, accuracy of analysis, accelerated in-flight experiment.

3 dwg

Gas sampling system // 2552267

FIELD: oil and gas industry.

SUBSTANCE: system contains casing-well, cylindrical sampler comprising three main parts, top part is manifold chamber, middle part is connecting coupling with female thread and groove connecting bottom and top parts, bottom part is receiving chamber for accumulation of gas supplied via side holes of the casing-well, receiving chamber and manifold chamber are covered with lids, above the connecting coupling a discharge tube is installed, under it a receiving tube is installed, above it a ball valve is installed, top discharge tube passes through the manifold chamber, lid and goes outside, on it the inlet union valve is installed to inject air in the manifold chamber and safety union valve for overpressure relief, the pneumatic chambers are located one above, and another below the inlet holes in the sampler casing, in top lid of the sampler the outlet valve is installed, casing pipe is made out of n pipes connected by outside thread coupling, with side holes of same diameter uniformly distributed along length of the casing pipe-well.

EFFECT: simplified design.

3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a solution for fixing biological cells. The fixing solution is intended for in vitro preservation of a cytological sample containing nucleated cells and erythrocytes. The solution contains 80-95 vol. % of a mixture of 590 ml normal saline, 10 ml polyethylene glycol (Carbowax®), 203 ml isopropyl alcohol, 193 ml pure ethanol, 0.01 vol. % sodium azide, and 5-20 vol. % buffered 4% formalin; pH of the fixing solution is in the range of 6.4 to 7.4.

EFFECT: preserving the integrity of nucleated cells.

2 cl, 2 dwg, 1 ex

FIELD: construction.

SUBSTANCE: static, dynamic or vibration sensing is carried out preliminary at the selected points to the depth from 1 m with respect to the top of the earth fill. At the same time the samples of compacted soil of undisturbed structure are selected in order to determine the moisture and density of skeleton of the specified soil from several drilled wells at points at a distance of not more than 1 metre in plan from sensing points. Laboratory researches of standard compaction with definition of compacting factor depending on the density of soil skeleton, are carried out on the selected samples of soils from the body of compacted fill. Construction of correlation dependence is performed between the specified values of compaction factor and values of the resistance to penetration of standard cone into the soil during sensing, taking into account determinations previously performed in the laboratory followed by evaluation of compaction quality of the earth fill.

EFFECT: improving the accuracy of definition and identifying the areas of non-compacted soil for its subsequent local postcompaction.

3 cl

FIELD: medicine.

SUBSTANCE: method includes the preparation of smear from peripheral blood with preliminary fixation with methyl alcohol, drying, washing with distilled water. After that, the smears are placed in a potassium chloride solution in a ratio of 0.57 g of potassium chloride per 100 ml of distilled water for 20 min and washed with distilled water. Additionally prepared is a mixture of solutions, prepared ex tempore, containing a solution "A" and "B". The solution "A" includes a 50% silver nitrate solution in an amount of 5 g of silver nitrate + 5 ml of distilled water. The solution "B" includes a 2% solution of gelatin on a 1% formic acid solution in an amount of 15.8 ml of distilled water + 0.2 ml of 100% formic acid + 4.0 ml of 10% gelatin. The solutions "A" and "B" are mixed in an amount of 5 ml of each, in darkness, with further submergence of the blood smears for 20 min in darkness in the thermostat at a temperature of 37°C with the further submergence of the smears into distilled water for 2-3 seconds. After that, they are twice subjected to a 8 min exposure in a 5% sodium thiosulphate solution in darkness in the thermostat at a temperature of 37°C. After that, they are washed successively with tap water and distilled water, after-staining is performed in the Romanovskiy dye for 30 min. After that, the smears are washed again with tap water, air-dried, placed in the Canadian balm and covered with a coverslip.

EFFECT: increased quality of smear staining and provision of a possibility to identify and further evaluate parameters of nucleolus organiser regions.

4 tbl, 6 ex

FIELD: agriculture.

SUBSTANCE: method of selection of horizontal soil monolith comprises embedding along the genetic horizons of nth thin-walled metal cylinder-monolith-selector of the ith diameter with a pointed lower end of a triangular shape. The selection of the horizontal soil monolith from the pit is carried out with the number of cylinders-monolith-selectors k, equal to where i - number of the cylinder diameter (n > i > 1), n - number of cylinders of different diameters, ki - the number of repetitions of the cylinder of ith diameter (ki > 3). And each time, prior to selection of the horizontal soil monolith the inner surface of each used cylinder-monolith-selector is greased with petroleum jelly, and the load on the cylinder-monolith-selector is performed in a direction perpendicular to the surface of the pit stepwise with fixing the load of each step. The set of devices for selection of the horizontal soil monolith comprises the said k-th number of thin-walled metal cylinder-monolith-selectors and a metal cylindrical nozzle on the cylinder-monolith-selector. The metal nozzle is provided with a cylindrical recess in one of its ends, which diameter is equal to the outer diameter of the cylinder-monolith-selector having a maximum diameter of n cylinder-monolith-selectors, and the axis of symmetry coincident with the axis of symmetry of the metal cylindrical nozzle. The set also comprises (n-1) washer with an outer diameter equal to the diameter of the recess and the thickness equal to the height of the recess in the end of the metal cylindrical nozzle with the ability of mounting of each of them to the recess, followed by fixing in it. The inner washer diameters are different and equal to the outer diameter of each of the (n-1) cylinder-monolith-selector, constituting a pair: washer-cylinder-monolith-selector. Set is provided with a screw press with a head and a heel of cylindrical shape and a shield with a recess on its axis of symmetry with the ability of mounting in it through the heel of the screw press. And in the other end of the metal cylindrical nozzle on the cylinder-monolith-selector on its axis of symmetry a recess of cylindrical shape is made, the diameter and depth of which correspond to the diameter and thickness of the head of the screw press.

EFFECT: improvement of quality of sampling soil of undisturbed placement and increase in the accuracy of determining the water-physical and filtration properties of soil on genetic horizons of the soil profile, reduction of time for selection of the monolith and the complexity of operations in selection of quality horizontal soil sample.

3 cl, 1 dwg, 1 tbl

FIELD: engines and pumps.

SUBSTANCE: device comprises a floating element 10, which is placed onto the sea surface and connected to a pump, rigidly fixed to the sea bottom or to massive floatage 8. The pump is made in the form of a cylindrical pipe-shaped vertically arranged chamber 1 semi-submerged into the sea, which in its upper and lower parts is equipped accordingly with lower 3 and upper 6 nozzles. At the lower nozzle 3 there is a hose 4 with certain length arranged in water depth. In the chamber there is a piston in the form of an inlet check valve placed on the stem 9, which is made as capable of passing water in the chamber only in direction from the lower nozzle to the upper one and is connected by means of the stem 9 with a floating element 10. The piston may be made within a membrane 12 adjacent to the plane of a disc 11 made with through holes, axes of which are parallel to the axis of the disc.

EFFECT: simplified design, expanded area of application of a device for water lifting.

2 cl, 1 dwg

FIELD: measurement equipment.

SUBSTANCE: invention relates to equipment for determining consumptions and periodic water sampling from different horizons of a peat deposit, which are fixed as to depth. The complex includes a well casing pipe with a cone tip and a water intake structure. Besides, a sampling unit includes a cylindrical housing, on which there located are two elastic rubber cuffs with diameter equal to well diameter; in the wall of the cylindrical housing there are side holes - a middle one - for water receiving from a working horizon and is located between two cuffs; an upper one is located above the upper cuff; the lower one is located under the lower cuff; upper and lower holes are of a transit type and connected to each other with a tube passing inside the cylindrical housing of the sampling unit; the lower part of the cylindrical housing is connected to the water intake structure through a flange attached to the cylindrical housing; the upper part of the cylindrical housing is connected to a bracket for lifting the sampling unit and the water intake structure connected to it, the diameter of which is lower than inner diameter of the well casing pipe; the well casing pipe is pipes from one to N, which are connected to each other with external threaded couplings and side holes made throughout length of the pipes.

EFFECT: simpler design.

2 cl, 2 dwg

FIELD: measurement equipment.

SUBSTANCE: invention relates to a measuring probe for measurement and taking samples in molten metal. The probe is provided with a measurement head located on a rod, which includes at least a temperature sensor and a sampling chamber. The latter is at least partially enveloped with the measurement head and includes an input channel passing through the measurement head. The input channel has an internal section with length L, which is located in the measurement head, and has minimum diameter D at least at one point in this internal section; with that, L/D2 ratio is less than 0.6 mm-1. Besides, the measurement head has counter pressure Pg of lower than 20 mbar, which is determined so that first a reference gas flow is passed via a pipe with two open ends, and pressure P1 is measured in the pipe. Then, the pipe is inserted with one end into the inlet channel of the measurement head; the same reference gas flow is passed via the pipe and pressure P2 is measured in the pipe, and counter pressure Pg of the measurement head is determined based on difference P2-P1.

EFFECT: improvement of quality of the obtained samples.

23 cl, 5 dwg

FIELD: physics.

SUBSTANCE: method includes placing liquid media and objects located in a medium inside a mechanical oscillatory channel system, having a nonlinear relationship between resonant oscillation frequency and amplitude, wherein the method includes maximum alignment of resonance curves of an ultrasonic vibration generator and the nonlinear resonance curve of the channel system itself by determining the nonlinear resonance curve of the channel system as the relationship between the amplitude of mechanical vibrations and frequency, determining the difference between the frequency of the generator and the resonant frequency of the channel system at the required amplitude of vibrations and, based on said difference, changing the resonant frequency of the channel system by changing the geometric dimensions of the sizes. If the difference in frequency exceeds about 1.5-2.0 times the width of the resonance curve of the generator, vibrations are generated at two or more different frequencies.

EFFECT: high efficiency of cavitational effect on a processed liquid medium and objects in the medium.

12 dwg, 1 tbl

FIELD: food industry.

SUBSTANCE: homogeneous milk product manufacture device consists of a mixing vessel with an appliance for dry milk components loading therein, a rotary disperser connected to the mixing vessel in the recirculation circuit via the recirculation pump, an inlet nozzle connected (via the doser pump) to a sonochemical reactor connected to the ultrasound generator. Additionally, the invention relates to a method for hydration of polar molecules of milk proteins amino acids in the homogeneous milk product preparation process performed in the homogeneous milk product manufacture device. According to the invention, into the mixing vessel one adds dry whole or defatted milk or dry milk whey or a dry milk protein concentrate and water preliminarily treated in the sonochemical reactor at mean amplitude of sound pressure no less than synperiodical cavitation mode amplitude; one spends 5…9 kilojoules of cavitation mode acoustic energy for treatment of 1 l of water.

EFFECT: invention allows to manufacture homogeneous milk products based on natural milk, buttermilk with addition of vegetal fats and dry whole or defatted milk or dry milk whey or a dry milk protein concentrate without excessive energy expenditure.

2 cl, 3 dwg

FIELD: aviation.

SUBSTANCE: invention represents the method to obtain the soluble concentrate from sideline products of reindeer antlers, comprising aqueous raw extraction, grounded up to the forced meat condition with particle size of 3-5 mm under the action of ultrasonic vibrations with frequency of 37 kHz with subsequent filtration and vacuum drying at temperature of 45°C and pressure of 0.9 atm, distinguished by the fact that the aqueous raw extraction is carried out at temperature of 35-36°C in the presence of pepsin ferment at its concentration in raw mixture: water of 0.5% during at least 3 hours, at ratio raw: water for tails 1:5, for male genital 1:4, for uteruses with embryos and amniotic fluid 1:2.

EFFECT: significant increase of final concentrate yield from sideline products of reindeer antlers.

3 ex, 2 tbl

FIELD: physics.

SUBSTANCE: method includes placing liquid media and objects located in a medium inside a mechanical oscillatory channel system, having a natural oscillation frequency, in which parametric resonances are excited or parametric excitation of self-oscillation is performed, setting as the cavitational processing efficiency criterion the oscillation amplitude of the channel system, determining optimum frequency of oscillation frequency of power exciters with experimentally predetermined natural and parametric oscillation frequencies.

EFFECT: shorter processing time, higher power of acoustic waves and higher efficiency of cavitational processing of liquid media and objects located in the media.

12 dwg

FIELD: technological processes.

SUBSTANCE: invention relates to devices for physical and chemical treatment by ultrasonic cavitation of molecular and colloid solutions, and also disperse systems, phases of which may include live forms, by initiation of sonochemical reactions in media of such solutions and cavitation erosion of their phases. A sonochemical reactor for treatment of liquids includes a working volume filled with liquid flowing through it and limited with the surface of the body, which belong to a single solid-state vibrating system, from metal by two emitting surfaces and a binding surface between them, at the same time the centre of mass of this system is the centre of its geometric symmetry, for which purpose emitting surfaces belong to acoustic waveguide transformers of identical shape, dimensions and mass, transmitting coherent cophased flat-elastic oscillations from both sides from sources into liquid at frequency of free elastic oscillations of this solid-state vibrating system from metal, into composition of which they are included, and binding length makes half of length of vibration wave in metal, from which it is made.

EFFECT: invention provides for increased acoustic capacity of a cavitation reactor and increased efficiency of liquid treatment in it due to reduced losses of energy of ultrasound exciting cavitation.

2 cl, 4 dwg, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to field of chemical technology of energy-saturated materials, namely to methods of utilisation of formed wastes of production of defective and expired products, and is intended for laboratory methods of trinitrotoluene decomposition. Method of trinitrotoluene destruction consists in influencing trinitrotoluene in water medium with alkaline chemical reagents - water solutions of sodium sulphite and sodium hydroxide with concentration 5-20%, with weight ratio trinitrotoluene: chemical reagent, equal 1:3-30, and simultaneous impact with ultrasonic fluctuations with frequency not lower than 20 kHz and intensity not lower than 2,5 W/cm2; and at initial temperature 40-50°C heating is realised due to absorption of energy of ultrasonic fluctuations to temperature 80-85°C.

EFFECT: invention provides complete decomposition of explosive substance, absence of toxic organic products and high rate of the process.

9 dwg, 1 tbl

FIELD: power industry.

SUBSTANCE: heat-mass-energy exchange method consists in formation of vortex annular flows of media, their direction parallel to each other with provision of partial contact of opposite directed external surface layers in radial and tangential directions to the depth providing their acoustical excitation due to deformation-shear interaction, and further combination of excited flows. One of the vortex annular flows is additionally directed in an opposite direction to the rest ones along their axes. A heat-mass-energy exchange device containing two pipes with tangential inlets, which are interconnected with each other by partial intersection along generatrixes, and an acoustical chamber; with that, tangential inlets and the outlet of one of the pipes are located in an opposite direction in relation to the tangential inlets and outlets of the rest pipes.

EFFECT: invention provides for additional excitation of flows in the zone of their contact and increase of heat-mass-energy exchange intensity.

2 cl, 6 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to obtaining biocompatible magnetic nano-particles and can be applied for therapeutic purposes, in particular, for fighting cancer. Method of obtaining nano-particles, including iron oxide and silicon-containing casing and having value of specific absorption rate (SAR) 10-40 W per g of Fe with field strength 4 kA/m and frequency of alternating magnetic field 100 kHz, contains the following stages: A1) preparation of composition of at least one iron-containing compound in at least one organic solvent; B1) heating of composition to temperature in range from 50°C to temperature 50°C lower than temperature of reaction of iron-containing compound according to stage C1 for minimal period 10 minutes; C1) heating composition to temperature between 200°C and 400°C; D1) purification of obtained particles; E1) suspending purified nano-particles in water or water acid solution; F1) addition of surface-active compound to water solution, obtained according to stage E1); G1) processing of water solution according to stage F1) by ultrasound; H1) purification of water dispersion of particles, obtained according to stage G1); I1) obtaining dispersion of particles according to stage H1) in mixture of solvent from water and water-mixable solvent; J1) addition of alkoxysilane into dispersion of particles in mixture of solvent according to stage I1); and K1) purification of particles.

EFFECT: invention makes it possible to obtain biocompatible magnetic particles with high value of specific absorption rate (SAR).

42 cl, 3 dwg, 9 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to a method for preparing a soluble concentrate of deer-breeding antler by-products. The method for preparing the soluble concentrate of deer-breeding antler by-products involving water extraction of raw materials when exposed to ultrasonic vibrations at a ratio of raw materials: water 1:3 for male deer tails and/or reproductive organs, 1:1 for uterus with foetuses and amniotic fluid; that is followed by filtration and vacuum drying, under certain conditions.

EFFECT: method provides higher yield of the end product and keeping the natural properties of the raw material and a high degree of water-solubility.

3 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the technology of processing mineral material and can be used to produce amorphous silicon dioxide from rice husks. The method producing amorphous silicon dioxide from rice husks involves washing rice husks with deionised water in an ultrasonic field in cavitation mode while heating to 90°C, for 10 minutes at frequency of 20 kHz and 20 minutes at frequency of 35-60 kHz, respectively. Carbonisation is then carried out, as well as grinding the ash and oxidising roasting in a reactor lined with quartz glass, while constantly stirring in a current of cleaned air and raising temperature at not more than 10°C/min.

EFFECT: invention enables to obtain, using an ecologically clean method, amorphous silicon dioxide with purity of up to 99,99%, specific surface area of up to 420 m2/g and particle size of 10-80 nm.

3 cl, 5 ex

FIELD: chemical industry; mining; food industry; pharmaceutical and perfumery industry.

SUBSTANCE: the invention is dealt with the field of the hypersonic cavitational desintegration of liquid mediums and may be used in food, chemical, ore mining, pharmaceutical and perfumery industries. The method provides, that a liquid flow is passing through a resonant cell of the cavitational reactor, where in the liquid is formed a stagnant acoustic wave with the given average value of a volumetric density of the power causing generation of a cavitation in it in the form of one or several stationary cavitational zones. Density of the potential energy evolving for a period of the acoustic wave, in any point of perimeter of any cross-section of the liquid flow inside the reactor is set not exceeding its peak value on the walls of the resonant cell. The reactor contains a resonant cell, a body, a diaphragm with an aperture placed in a plane parallel to the oscillation shifts of the resonant cell walls. Coordinates of points of the perimeter of the minimum area of the cross-section of the reactor in the plane parallel to oscillating shifts of the walls of the resonant cell, are determined by an equation. The technical result is an increase of dispersion, homogeneity, intensifications of reactions, synthesis of new compounds and increase of their activity.

EFFECT: the invention ensures increased dispersion, homogeneity, intensifications of reactions, synthesis of new compounds and an increase of their activity.

2 cl, 7 dwg

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