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Cartridge for analyses with magnetic particles. RU patent 2505816.

Cartridge for analyses with magnetic particles. RU patent 2505816.
IPC classes for russian patent Cartridge for analyses with magnetic particles. RU patent 2505816. (RU 2505816):

G01N33/53 - Immunoassay; Biospecific binding assay; Materials therefor (medicinal preparations containing antigens or antibodies A61K; haptens in general, see the relevant places in class C07; peptides, e.g. proteins, in general C07K)
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FIELD: chemistry.

SUBSTANCE: cartridge (100) for detecting target components in a liquid sample comprises: a sample chamber (SC); at least two reservoirs (131, 132) filled with magnetic particles(MP, MP'), which are specific for different target components; at least two sensitive zones (121, 122) for detecting magnetic particles and/or target components, wherein magnetic particles (MP, MP') of different reservoirs primarily reach different sensitive zones while migrating into the sample filling the sample chamber under the effect of an activation magnetic field (B). The group of inventions also relates to a method of detecting target components using said cartridge, a device for detecting target components having said cartridge, a magnetic field generator and a sensor unit for detection inside the cartridge and to use of said device for molecular diagnosis, biological analysis of samples or chemical analysis of samples.

EFFECT: group of inventions enables to conduct multiple analyses in a single chamber without cross-reactions.

14 cl, 7 dwg

 

THE TECHNICAL FIELD TO WHICH THE INVENTION RELATES

The present invention relates to the print cartridge and a method for the detection of target components in a liquid sample with the help of the magnetic particles to the device sensor, containing such a cartridge, and to use such cartridge and sensor device.

PRIOR ART

Magnetic sensor device known from WO 2005/010543 A1 and WO 2005/010542 A2, for example, you could use in for detecting molecules, for example, biological molecules, marked magnetic balls. Magnetic detector unit is equipped matrix gauge block, containing wires for the generation of magnetic field sensors and giant magnetoresistance effect (GMR) to detect spurious fields generated by magnetized balls. Signal GMR specifies the number of balls, associated with the neighboring contact surface.

In WO 2003/062787 uncovered a process in which the magnetic microspheres are sorted into different groups according to their magnetic moments, and different agents-receptors join different groups. After preprocessing, all magnetic microspheres are filled with a model that allows you to target specific components to communicate with agents-receptors. At the last stage, magnetic microspheres again divided into different groups according to their magnetic moments, and the linking of target components detected in separate groups, for example, by the presence of fluorescence.

A BRIEF DESCRIPTION OF THE NATURE OF THE INVENTION

The objective of the present invention is to provide a means for the detection of target components in the sample with the help of magnetic particle, and it is desirable to have the ability to simultaneously detect different target components with high accuracy.

This objective is achieved through the cartridge according to claim 1, device section 12 of the sensor, the fashion paragraph 14 and utilization according to item 15. Preferred options implementation disclosed in dependent clauses.

Cartridge, according to the present invention, serves for detection of target components in a liquid sample, for example, atoms, (bio)molecules, complexes, narcotic drugs (especially drugs), nanoparticles, microparticles, cellular fractions or cells in body fluids such as blood, saliva or urine. Detection of target components can be qualitative (yielding only information presence/absence) or, preferably, quantitative (yielding, for example, the concentration of the target components in the sample). The cartridge is usually a cheap plastic piece, made by a method of punching under pressure, which you can fill in the test sample, insert in a compliant reader to produce the necessary measurements, and disposed of. In General, the term "cartridge" means the device specified by the contents of the following components:

a) "the camera for samples, which you can fill in the test specimen and where you can create "the magnetic field of the activation" of this configuration. Sample chamber is usually an empty cavity; it can be an open cavity, sealed cavity or a cavity is connected to other cavities TV connection liquids.

Configuration of the magnetic field activation is set to the spatial arrangement of its lines of the magnetic field and the value of a field (i.e. the direction and length of the vectors of the magnetic field). To define a cartridge configuration of the magnetic field activation is considered a predetermined and fixed relative to the cartridge.

The magnetic field of the activation can be generated by means of internal funds cartridge and/or external funds. The cartridge design in any case should allow to create a magnetic field to activate this configuration in the chamber for the sample, i.e. the sample chamber may, for example, not be magnetically shielded. The magnetic field of the activation can affect migration of magnetic particles in the cell for samples under the action of forces, for example, due to a non-zero gradient fields. Note that the magnitude of the vectors of the magnetic field usually exceed a certain threshold, to magnetic influence was strong enough (in comparison with other impacts, for example, gravity).

b) at least two "tank" for magnetic particles, which are soluble in the sample. Magnetic particles can, in particular, contain complexes, nanoparticles, microparticles etc., magnetized or likely to be magnetized in an external magnetic field; it is most preferable, they contain balls with a biocompatible coating on its surface.

Each tank can be coherent or incoherent two-dimensional/three-dimensional area. The tanks can be pre-filled with magnetic particles or may be initially empty (i.e. ready to fill particles).

c) At least two "sensitive areas" (areas)in which the magnetic particles and/or target components can be qualitatively or quantitatively) detect, for example, if they enter into these areas through liquid sample in which they are divorced. Sensitive areas may, for example, be placed on a transparent wall of the chamber for samples so that they can be optically available from the outside.

In addition, the ratio between the camera for samples, tanks, sensitive areas and to the data of the magnetic field of the activation should be such that the magnetic particles of different tanks mainly reached different sensitive areas (if they even reach the sensitive area) in migration in the sample that fills the camera for samples, under the influence of magnetic field is activated. Since the motion of microscopic particles always subjected to the random effects, it is sufficient if this condition "predominantly" is performed, i.e. for more than 90% of the total number of magnetic particles, preferable for more than 95%, the most preferable for more than 99%.

Described cartridge enables the parallel testing of a sample of magnetic particles from different reservoirs with the help of different sensitive areas, in which the magnetic particles can be exposed to a magnetic field of activation (for example, to move in the right direction). Favorably that the influence of the magnetic field of the activation of the magnetic particles is such that the magnetic particles of different tanks are not mixed in the course of migration to sensitive areas and in the course of interaction with the sensitive areas. Thus, the magnetic field of the activation forms a certain virtual wall (only) for magnetic particle, essentially separating chamber for samples on various , between which there is no exchange of magnetic particles. However, in fact, the sample chamber remains connected displacement, which may be freely distributed liquid sample.

Note that the magnetic particles from one tank can migrate in accordance one to several different sensitive areas, although usually between the tanks and the sensitive areas there exists a bijective correspondence.

In the General case, the configuration of the magnetic field of the activation can be arbitrary. However, in many cases, field gradient, i.e. the gradient of (scalar) amplitude of intensity of the magnetic field is perpendicular to the sensitive areas (and, optionally also to the tanks). More specifically, the sensitive areas can be placed in a common plane, and the gradient of the magnetic field activation crosses the plane essentially perpendicular (i.e. at an angle of about 70 degrees to about 110 degrees, preferably from about 80 degrees up to about 100 degrees). Since the magnetic particles tend to move in the direction of the gradient of the magnetic field, the configuration described here provides the movement of the particles is perpendicular to sensitive areas (and tanks).

Tanks cartridge may be, for the use of a cartridge, fill in the homogeneous magnetic particles (material, size distribution, coverage, etc). However, it is preferable that at least two tanks were filled with magnetic particles of a different type, in particular, the magnetic particles, which are specific to the different target components. Magnetic particles of two tanks may be covered with different molecules, which form a (bio-)chemical bonds with different target components in the sample and/or with different binding sites in sensitive areas.

Similar comments could be made in relation to the sensitive areas, i.e. it is preferable that at least two sensitive areas were specific to the different target components. These zones can, for example, be covered with binding sites (molecules of capture), which is specific form a relationship with different target components in the sample. This allows you to simultaneously scan the sample in relation to different target components.

The relative positioning of tanks and sensitive areas completely arbitrarily, provided that, in the presence of the magnetic field of the activation guaranteed desired split moving of magnetic particles from the tanks in sensitive areas. In a preferred embodiment, tanks and sensitive areas are on different internal surfaces of the camera for samples, in particular, the surfaces facing each other (for example, on the top and bottom surfaces of the camera for samples). In this case, the magnetic particles will migrate through all chamber for samples to reach sensitive areas that maximizes the probability of reaction between the magnetic particles and destination components in the sample.

In another embodiment, tanks overlap (fully or at least partially) with the relevant sensitive areas. In this case, the magnetic particles are in the "right" sensitive areas from the beginning of the measurement and the magnetic field of the activation should ensure that they do not leave scope of this sensitive zone and reached another sensitive area.

When the magnetic particles move from the different reservoirs in the relevant sensitive areas, they can interact with each other, for example, under the influence of magnetic and/or electrostatic forces. In order to avoid undesirable consequences of such interaction for migration magnetic particles, it is preferable that the tanks were filled with magnetic particles in quantities, which is essentially the balance of interaction between the magnetic particles of different tanks in the course of their migration through the sample. In a symmetrical two tanks and two sensitive areas, for example, you can use equal amounts of magnetic particles in both tanks to make the interaction between the magnetic particles also symmetric.

Sample chamber, preferably, is part of a liquid system or connected to a liquid system through which the sample flow through you can induce through the camera for samples. This allows you to fill in the chamber for liquid samples sample, when you need to take a measurement.

In the simplest case, the cartridge can be a device (for example, shaped plastic piece), which essentially consists of a chamber for samples in which some are tanks and other areas are sensitive areas. In a more complex variant of implementation, the cartridge contains a built-in generator of the magnetic field, for example, the coil and/or wire that is embedded in the wall of the cartridge, through which you can pass the electric current to create a magnetic field. Generator magnetic field, in particular to adapt to generate a magnetic field activation, which affect the movement of the magnetic particles from the tanks to the sensitive areas. However, the generator of the magnetic field can additionally or alternatively to serve other purposes, such as magnetic excitation of magnetic particles in the sensitive areas for the generation of spurious fields that give out the presence of these particles appropriate magnetic sensor.

According to other variant of implementation, the cartridge may contain an integrated sensor unit for detection of magnetic particles and/or target components in sensitive areas. Integration of such sensor unit in the cartridge has the advantage of minimizing the distance between the sensor and the sample and in providing certain conditions.

Invention additionally refers to the device sensor for detection of target components in a liquid sample containing the following components:

a) cartridge for the above type, i.e. cartridge camera for samples and at least two reservoirs and sensitive areas, where the magnetic particles of different tanks will reach different sensitive areas, migrating under the influence of a magnetic field of activation;

b) magnetic field generator to generate a magnetic field activation inside the cartridge. Generator magnetic field, for example, can be implemented in the form of a permanent magnet or an electromagnetic coil and can be integrated into the cartridge or place outside of it.

c) block sensor for detection of magnetic particles and/or target components inside the cartridge. Again, the sensor unit can be (at least partially) is integrated into the cartridge or be a separate component of the sensor device.

As the cartridge is an important component of the device sensor, reference is made to the above description of the print cartridge for more information about the details, advantages and additional improvements of the device sensor.

Cartridge and/or device sensor can, optionally, include optical, magnetic, mechanical, acoustic, thermal and/or electrical power sensor. Magnetic sensor unit may, in particular, contain the coil, a Hall sensor planar sensor Hall, sensor, a SQUID (superconducting quantum interference sensor), magnetic resonance sensor, sensor, or magnetoresistive sensor like described in the WO 2005/010543 A1 or WO 2005/010542 A2, especially the sensor GMR (giant magnetoresistive effect), (TMR tunneling magnetoresistance effect) or AMR (anisotropic magnetoresistive effect). Optical sensor unit can be, in particular, to adapt to detect changes in the output light beam, which occurs as a result of frustrated total internal reflection, due to the presence of target particles on the sensitive surface. Other concepts optical, mechanical, acoustic and thermal sensor described in the WO 93/22678, are incorporated herein by reference.

In addition, the invention relates to a method for the detection of target components in a liquid sample that contains the stages at which (and their sequence numbering not necessarily correspond to the order of their implementation):

fill camera for samples cartridge model. Cartridge, in particular, can be described above type;

allow magnetic particles pass through a sample of at least two tanks in at least two sensitive areas. In this context, the term "permit" means that provide the conditions under which the magnetic particles can migrate through the sample. Such conditions may include, for example, sufficient time, the proper temperature, the initial provision of a sufficient amount of magnetic particles in the tanks, breeding of magnetic particles in the sample etc.;

create a magnetic field to activate this configuration in the chamber for the samples so that the magnetic particles of different tanks mainly migrated in different sensitive areas. The magnetic field of the activation can, optionally, be present during the entire procedure;

detect magnetic particles and/or target components in sensitive areas.

Method contains, in General, the steps that can be performed by using the print cartridge and the device sensor to the above type. Therefore, reference is made to the previous description for more information about the details, advantages and improvements of this method.

Invention additionally refers to the use of the above cartridge and/or sensor device for molecular diagnostics, biological sampling and chemical analysis of samples, food analysis and/or analytical analysis. Molecular diagnostics, for example, can be carried out with magnetic beads or fluorescent particles that are directly or indirectly connected to the target molecules.

BRIEF DESCRIPTION OF DRAWINGS

These and other variants of the invention follow from and explained with reference to the option(s) implementation described below. These options for implementation will be described in the examples with reference to the attached drawings, in which:

Figure 1 depicts the view from the top of the first cartridge according to the present invention, in which tanks for particles and sensitive areas are located in the upper part and the lower part, respectively;

Figure 2 cutaway view of the first cartridge line II-II in figure 1;

Figure 3 - the view from the bottom to the top of the first cartridge;

Figure 4 - the General view of the camera for the first samples of the cartridge;

Figure 5 - the General view of the camera samples for the second cartridge according to the present invention, in which tanks for particles and sensitive areas of overlap;

6 - General view camera for samples third cartridge according to the present invention, in which tanks surround particles sensitive areas;

Fig.7 - various charts experimental test of the cartridge and method according to the invention.

DESCRIPTION OF THE INVENTION

Similar legend or legends, differing in integral multiples of 100 indicate the drawings identical or similar components.

A roadside check on the availability of narcotic drugs is a typical use of portable magnetic biosensor. Such check will be used on the road (similar to the test for the presence of alcohol vapors in exhaled air) and must allow them to establish the existence of up to five drugs in one sample of saliva for one minute. A check must be reliable and easy to use. Preferably, so that it can be done with the help of only one operator actions (sample and insert it into a card reader) without any training police.

Illegal drug in the General case, is a small molecule, able to communicate only with one molecule of capture (antibody). For this reason, the detection of such medications can be used format or competitive analysis. In the analysis of the first type of target molecules homologues are present on the surface of the sensor. These target molecules homologues compete with the target component (which must be present in the sample) for education connection with the molecule capture, which is present on the magnetic marker. In the analysis of the second type target homolog is present on the magnetic marker, and covered with a marker competes with the target component (which must be present in the sample) for education connection with molecules capture (antibodies)that are present on the surface of the sensor.

In the above scenarios, five different molecules capture should be present at the magnetic marker or on the surface of the sensor (depending on the format of the analysis), the capacity to detect five drugs. In addition, five different target homologues must be present on the surface of the sensor or on magnetic marker (depending on the format of the analysis). Because the drug is usually a small molecule, linking with other molecules through a receptor-ligand (for example, binding to the coated antibody)in the General case is not very specific. As a result, cross reaction occurs (for example, magnetic marker, covered with binding molecules for type A, forms a link with a target which is homologous to type B). For instance, the magnetic particles coated antibodies will bind to the BSA- on the surface of the sensor, but also will greatly communicate with BSA-methamphetamine. Thus, the addition of magnetic particles with antibodies in the matrix of sensitive areas, where at least one sensitive area covered BSA-amphetamine and one sensitive area covered BSA-methamphetamine, will demonstrate a large output of the sensor to the sensitive zone, covered with BSA-amphetamine, but also will demonstrate significant output signal for the sensitive zone, covered with BSA-methamphetamine. So most of the testing systems, analyses, showing the cross-react physically separated by analysis in the individual test strips/tubes. It's a tough decision, because the test sample should be divided by different test strips/tubes that increase the complexity of the test device and increase the amount of sample needed for the implementation of all the tests.

Proposed here for the solution of the above problems is based on the fact that a magnetic , you can use the activation provided by magnetic markers (balls). To do this, the orientation of the magnetic forces and relative location of the magnetic particles are selected so that different types of particles separated.

Figure 1-4 shows the cartridge 100 according to the first realization of the invention. Cartridge 100 contains the following components:

- upper part 101, for example, in the form of a plastic part, produced by die molding under pressure. The upper part contains 101 funnel input channel 102 for the sample on its inner side, which leads in liquid channel 104. This channel 104 delves into the lower side and ends liquid siding, and a vent 105.

In addition, the upper part 101 contains two adjacent tank 131, 132, filled in (different) magnetic particles MP, MP'.

- the lower part of 103, which are attached to the top of the 101 and performed, for example, in the form of extruded connecting devices (MID). The lower part contains 103 tapered hole that forms the camera for samples SC under the tanks 131, 132.

- block 110 sensor that is attached to the underside of the bottom of 103 to close the camera, SC for samples. Block 110 sensor provides a tool for the detection of target components and/or magnetic particles in sensitive areas 121, 122 on its surface. Block 110 sensor can be, for example, just transparent body, through which the input light beam L1 from the light source (not shown) can be applied at the border section between this body and the camera SC for samples, where he is totally internally reflected in the output light beam L2. Target components and/or magnetic particles, which form a link on the boundary, will determine a frustrated total internal reflection (FTIR), which can be detected in the output light beam L2 with a detector of light (not shown).

Alternatively, the sensor unit may also contain sensor, for example, GMR sensor.

Block 110 sensor can be in electrical contact with the reading device (not shown) through the pads 111 on flexible electrical foil (MID).

Furthermore, figure 2 shows a generator 1 of the magnetic field, located beneath the unit 110 sensor for the generation of magnetic field B activation with a predefined configuration inside the camera SC for samples.

Figure 4 shows the General view from the camera perspective SC for samples, relative positions of two tanks 131, 132 at the top of the camera for samples and two corresponding sensitive areas 121, 122 in the bottom of the camera for samples. Each of sensitive areas 121 and 122 contains many spots BS and BS' binding, respectively. Spot BS BS' connect at each sensitive area covered by the same molecules seizures while spot BS and BS' linking different sensitive areas covered by different molecules capture. Molecules capture you can, for example, to besiege in small spots by inkjet printing.

According to figure 4, the main component of the magnetic force is directed in the (negative) z direction, i.e. perpendicularly to the surface of the sensor, and balls MP, MP' in the tanks are located in the z-direction precisely over their respective sites grip on the surface of the sensor. Planar components (in x and y direction) are much smaller. The magnetic field lines can, preferably, to Orient in the x direction (with their gradient points in the direction z)that creates a chain of magnetic particles along these lines. This creates a force of repulsion between the chains of magnetic particles in the y-direction, which helps to maintain two sets of balls separated.

When the center of the magnet 1, which generates a field is well aligned with the center of the surface binding, magnetic beads not cross the center of the (constant magnetic point), which prevents the mixing balls magnetic means. Mixing due to the diffusion can be neglected, because the magnetic force can be done quite large. However, since the magnetic balls can cross the center of the magnet due to the repulsive electrostatic and/or magnetic forces between the magnetic particles and chains of particles, respectively, both tanks preferably fill in approximately equal numbers of magnetic balls for the formation of a kind of "back pressure".

Note that the magnetic field that can be used for the magnetization of the balls in the course of the procedure of detection by the sensor GMR in sensitive areas, usually highly localized and does not lead to undesirable mixing balls.

Note also that, of course, more than two types of balls can be precipitated in tanks, one after another, depending on the availability of free space. According to this method, multiple analyses that will cross-react with each other in case of mixing them, you can make the same reaction chamber, without receiving any cross-reactions.

Figure 5 shows the second variant of the implementation of the cartridge 200. Different magnetic beads coated with different binding molecules or different target , used to separate tanks 231 and 232, respectively, which are located on the same surface, and sensitive areas 221 and 222, and overlap with them. The advantage of this design is that all of the biomaterial fit in one part of the cartridge (figure 5 lower part 203, containing the bottom of the camera SC for samples). Therefore, this part can be optimized for the imposition of biomaterials, while another part (201) you can optimize for example, for quick filling of liquid channels. This optimization can, for example, contain (which may impede the application of biomaterial in small spots). Another advantage is that the magnetic beads are very close to the surface of the sensor, and to move from the top down to the surface of the sensor does not require time, which reduces the analysis time.

On 6 shows a third option is the implementation of the cartridge 300. Again, tanks 331 and 332 for the balls are in the lower part of the chamber the SC for samples, i.e. at the bottom of the 303. However, instead of deposition balls on top of a printed spots BS, BS' bind that overlap with sensitive areas 321 and 322, they are deposited after the printed spots binding. Bulbs can precipitate after spots for linking in the direction of the x and/or y. Spot binding you can also print on a circular layout, after which the bulbs can precipitate after their respective customers capture, in a somewhat wider circle or ring that surrounds them.

Figure 7 shows the results of the experiments, which demonstrate the ease of implementation of magnetic separation of two different reservoirs (bays). In the experiment, competitive analysis was carried out in the system of the optical sensor FTIR. Five drugs (opiates OPI, amphetamine AMP, methamphetamine MAMP, cocaine COC, THC tetrahydrocannabinol) and the reference substance (Biotin BIOT) were measured simultaneously. Full-time analysis was one minute. Magnetic particles were present in the dry form, reagents were treated, filtered saliva (dry Regents).

particles were coated with monoclonal anti-drug antibodies. For the analysis of amphetamine, Biotin and opiate used particles ADEM electronics 500 nm, covered COOH. For the analysis of methamphetamine, cocaine and tetrahydrocannabinol used balls ADEM electronics 300 nm NH 2 . Particles were again scattered in a buffer. Balls 500 nm of each type were again scattered at 1% of weight. (full concentration balls 3 wt% a mixture of 1), then the balls 300 nm were again dispersed in 2% of the weight. (COC and THC) or 1% of weight. (full concentration balls 5%, mixture of 2). Then, 2 x 75 nl mix 1 and mix 2 was applied to the liquid top part containing the two marks, one of the mixture in each channel. Optical substrate was prepared for the detection of target molecules by printing spots BSA-drug. The upper and lower part of the biosensor were collected using a tape, and sensors supported in laboratory conditions at room temperature. The next day, the cartridges were tested through the implementation of a competitive analysis in optical biosensor system. The analysis contained filtering saliva (a group of 10 volunteers) through the stack of the filter-hydroxyapatite (HAP)filter where filters contain dry Regents. Then the filtered saliva added narcotic drugs in different concentrations and introduced in the cartridge by Autonomous filling up through the capillary channel. Then magnetic particles were again scattered, then attached to the surface of the sensor (using coil system activation). After a predetermined time, field of magnetic attraction removed. Another magnetic field over the cartridge used for pulling the disjoint balls with the surface of the substrate. Full-time analysis (filling, re-scattering and magnetic activation) amounted to 60 (1 with filling the cartridge, 14 with the re-dispersion balls, 45 with activation). Then measured the cross-reactivity.

When the ten negative samples (all tests on narcotic drugs negative) and ten positive samples on narcotic medication (i.e. one test of a medicinal product is negative while the other is strictly positive) and measured the mutual influence. Concentration for a positive reaction was selected as 1 mg/ml (for opiates, amphetamine, methamphetamine, Biotin), 5 mg/ml (cocaine) and 50 mg/ml (tetrahydrocannabinol). Figure 7 shows the six charts the changes of the optical signal spots on optical substrates (in %) for mixtures of saliva containing all drugs except for one that is specified in the title of the chart (i.e. without Biotin BIOT, without amphetamine AMP, without opiates OPI, without methamphetamine MAMP, without THC and without cocaine COC; horizontal axis: the number of measurement).

All the spots, positively reacting to a hallucinogenic drug, have signal changes less than 10%, thus demonstrating a very small mutual influence. In addition, the magnetic particles coated with antibodies, are not associated with BSA-methamphetamine. If the division between the two rows was not good spot BSA-methamphetamine would demonstrate signals, similar signals from stains BSA-amphetamine, thus, showing good separation between tests for amphetamine and methamphetamine.

Thus, a solution was proposed to support a magnetic beads separate during linking. Thanks to the placement of magnetic balls in at least two different tanks which are oriented perpendicular to the direction of the magnetic field lines, groups of beads do not show any mixing in the course of analysis. This allows multiple analyses in one chamber without any problems with cross-reactions. Among the advantages of this approach include:

- no cross reactions;

- easy cartridge: single channel, one camera;

- a small volume of the sample: the sample should not be separated.

Although the invention described above with reference to the specific options for implementation, there are various modification and extension, for example:

- the sensor can be any suitable sensor for detecting the presence of magnetic particles on or near the surface of the sensor, on the basis of any property of a particle, for example, it can detect using magnetic media (for example, magnetostriction, Hall effect, coils), by optical means (for example, imaging, fluorescence, chemiluminescence, absorption, scattering, methods of decaying fields, surface plasmon resonance Raman scattering etc), acoustic detection (for example, surface acoustic wave, bulk acoustic wave, bracket, quartz crystal, etc.), electric detection (for example, conductivity, impedance, current measurement, redox cycle), their combinations and etc.:

- magnetic sensor can be any suitable sensor based on the detection of the magnetic properties of particles on or near the surface of the sensor, e.g. coils, of magnetoresistive sensor, sensor, Hall sensor, planar sensor Hall, ferrozond sensor, a SQUID, magnetic resonance sensor etc.:

- apparatus and method can be used as a fast, reliable, and easy-to-use biosensing applied in field conditions, for small sample volumes. Reaction chamber may be a single for use with compact reading unit containing one or more of the means of generation field and one or more means of detection. In addition, the device, methods and systems of the present invention can be used in automated testing with high efficiency. In this case, the reaction chamber is, for example, plate with holes or cuvette for installation in the automatic tool;

- under the nanoparticles refers to particles having at least one size between 3 nm up to 5000 nm, preferably, from 10 nm up to 3000 nm, preferably, from 50 nm to 1000 nm.

Finally, you must specify that in the application of the term "may contain" does not exclude the existence of other elements or phases, the use of the names of elements or phases in the singular shall not exclude the presence of their multiplicity, and that one processor or other device can perform the functions of several funds. Invention relies on all the signs novelty and each combination of distinctive features. In addition, the legend, the claims should not be considered a restriction of its volume.

1. Cartridge (100, 200, 300) for the detection of target components in a liquid sample, containing (a) the camera (SC) for samples that can be filled with sample and in which you can create a magnetic field () is activated, (b) at least two of the tank (131 and 132, 231 and 232, 331 and 332) for magnetic particle (MP, MP'), which are soluble in the sample, wherein said at least two of the tank (131 and 132, 231 and 232, 331 and 332) filled magnetic particle (MP, MP'), which are specific in relation to different target components, c) at least two sensitive areas (121 and 122, 221 and 222, 321 and 322), which can be used to detect magnetic particles and/or target components, magnetic particle (MP, MP') different tanks mainly reach different sensitive areas, migrating in the sample that fills the camera for samples, under the influence of a magnetic (B) field activation.

2. Cartridge (100, 200, 300) according to claim 1, characterized in that sensitive areas (121 and 122, 221 and 222, 321 and 322) are in a common plane, the gradient of the magnetic field (In) activation crosses the plane perpendicular.

3. Cartridge (100, 200, 300) according to claim 1, wherein at least two sensitive areas (121 and 122, 221 and 222, 321 and 322) are specific to the different target components.

4. Cartridge (100) according to claim 1, characterized in that the tanks (131, 132) and sensitive areas (121, 122) are located on different internal surfaces of the camera (SC) for samples, in particular on the opposite surfaces.

5. Cartridge (200) according to claim 1, characterized in that the tanks (231, 232) overlap with relevant sensitive areas (221, 222).

6. Cartridge (300) according to claim 1, characterized in that the tanks (331, 332) are located on the same surface as the corresponding sensitive areas (321, 322), behind them.

7. Cartridge (100, 200, 300) according to claim 1, characterized in that the tanks (131 and 132, 231 and 232, 331 and 332) filled magnetic particle (MP, MP') in amounts which, in essence, balance the interaction between the magnetic particles of different tanks, when the magnetic particles migrate in the sample.

8. Cartridge (100, 200, 300) according to claim 1, wherein the camera (SC) for the samples is part of system (103, 104, 105) or connected to it, whereby the sample flow can be directed through the camera for samples.

9. Cartridge (100, 200, 300) according to claim 1, characterized in that it contains a built-in generator of a magnetic field.

10. Cartridge (100, 200, 300) according to claim 1, characterized in that it contains an integrated unit (110) sensor for detecting magnetic particle (MP, MP') and/or target components in sensitive areas (121 and 122, 221 and 222, 321 and 322).

11. Device for detection of target components in a liquid sample containing a) cartridge (100, 200, 300) according to claim 1, b) generator (1) of the magnetic field for the generation of magnetic (B) field activation inside the cartridge, c) unit (110) sensor for detecting magnetic particle (MP, MP') and/or target components inside the cartridge.

12. The device according to claim 11, wherein contains at least one optical, magnetic, mechanical, acoustic, thermal or electric sensor unit, in particular the coil, a Hall sensor planar sensor Hall, sensor, a SQUID, magnetic resonance sensor, sensor or magnetoresistive sensor (110), such as the GMR, TMR or AMR.

13. Method of detection of target components in a liquid sample containing the steps to: fill the camera (SC) for samples cartridge (100, 200, 300) model, allow the magnetic particles (MP, MP') migrate across the sample of at least two tanks (131 and 132, 231 and 232, 331 and 332) in at least two sensitive areas (121 and 122, 221 and 222, 321 and 322), wherein said at least two of the tank (131 and 132, 231 and 232, 331 and 332) filled magnetic particle (MP, MP'), which are specific to the different target components, create magnetic (B) field activation in the chamber for samples to magnetic particle (MP, MP') from different reservoirs mainly migrated in different sensitive areas, detect magnetic particles and/or target components in sensitive areas.

14. Use the device on item 11 for molecular diagnostics, biological sampling and chemical analysis of samples.

 

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