RU2774307C1 - Biosensor for indication of biopathogens - Google Patents

Abstract

FIELD: fine particles indicating.

SUBSTANCE: invention relates to means for indicating fine particles (FP) of nano and micron size in suspension: proteins, viruses, bacteria and can be used in the field of medicine, virology, microbiology, biotechnology, toxicology, biology. The biosensor for indicating biopathogens includes a silicon crystal in the form of a substrate on which conductive electrodes are located, which are the source and the first drain of the transistor, a sensitive element, which is the first nanowire, made in a thin-film silicon-on-insulator structure on a silicon substrate and placed between two conductive electrodes source and drain electrodes to form a transistor channel, dielectric coatings that provide insulation for the conductive electrodes. In addition, on the silicon substrate on the other side of the source electrode, symmetrically to the first drain electrode, there is a second drain electrode and a second nanowire installed between the source electrode and the second drain electrode, and on both sides of one of the nanowires, a pair of lateral electrodes for dielectrophoretic concentration of viral particles are installed, located with a gap relative to the specified nanowire and with an axial displacement relative to each other, or on both sides of both nanowires, pairs of lateral electrodes are installed for dielectrophoretic concentration of viral particles, located with a gap relative to of these nanowires and with axial displacement relative to each other.

EFFECT: invention provides an increase in the sensitivity of the biosensor for the indication of biopathogens.

2 cl, 1 ex, 6 dwg

Description

The invention relates to means for indicating fine particles (MP) of nano and micron size in suspension: proteins, viruses, bacteria and can be used in the field of medicine, virology, microbiology, biotechnology, toxicology, biology.

The prior art at the present time, modern analytical methods for the indication of viruses (enzymatic immunoassay, immunochromatographic, polymerase chain reaction (PCR), analysis, etc.) have the highest level of sensitivity. They are able to detect single viral particles and their fragments in suspension with a fraction of a microliter, to identify specific sections of DNA, RNA of specific pathogens [Shchelkunov S.N. genetic engineering. - Novosibirsk: Sib. univ. publishing house, 2004. - 496 p.; ill. - ISBN 5-94087-098-81. For example, the enzyme immunoassay method provides high speed and convenience in carrying out a diagnostic reaction [Egorov A.M., Osipov A.P., Dzantiev B.B., Gavrilova E.M. Theory and practice of enzyme immunoassay. M.: Publishing house "Higher school", 1991. S. 3-42.].

The immunochromatographic method at a relatively low cost allows for a visual assessment of the result of the indication of pathogens [Immunochromatographic analysis https://monographies.ru/en/book/section?id=99291.

The PNR method significantly increases the low concentrations of certain nucleic acid fragments (DNA or RNA) in the biological material (sample) and reveals specific sections of DNA or RNA, which gives a direct indication of the presence of the infectious agent.

However, the accumulated theoretical knowledge indicates that a significant part of viruses and low molecular weight proteins still eludes detection methods due to their natural low concentration. As a result, the reliability of the indication acquires a random value.

The search for new principles and means of indicating pathogens is still relevant for early medical diagnosis of a disease.

A competitive alternative to the above analytical means of indicating viruses can be offered by nanowire biosensors based on silicon-on-insulator structures with nanowire sensors (SOI-NS) [K.A. Highly sensitive detection of low-copy proteins using a nanowire biosensor. 2019. Dissertation for the degree of candidate of biological sciences.]. The development of technical means for express indication of pathogens using SOI-NP sensors is carried out in the direction of improving the characteristics of their sensitivity, reliability, simplicity, the use of dielectrophoresis, concentration devices.

A known method and device for manipulating polarizable analytes using dielectrophoresis (patent application US 20040011650, Fig. 1). In the device, the concentration module includes a microfluidic channel with inlet and outlet ports and a structural constriction. Two electrodes that generate an electric field for manipulation of analytes are located upstream and downstream. Using the dielectrophoresis method, target analytes are concentrated or separated from contaminants and transported to the detection module. EFFECT: invention allows to increase the value of detection of target analytes. However, the method and device have a number of disadvantages. The first disadvantage of this method is the high quality requirements for the analyzed suspension of the analyte. The suspension should have low electrical conductivity, micron-sized particles should be completely absent. They can lead to a partial or complete stop of the suspension flow through the microfluidic channel. The second disadvantage is the difficulty in realizing the stability of the volumetric flow rate and the magnitude of the linear velocity of the flow of the test liquid through the microfluidic channel. The dielectrophoretic force acting on the target analyte between two electrodes generating an electric field for manipulation of the analytes is highly sensitive to the specified suspension flow parameters. The third disadvantage is the extremely difficult procedure for removing contaminants or air bubbles from the microfluidic channel. The fourth disadvantage is the problem of sterilization, washing with a neutralizing solution and sample preparation of the microfluidic channel for the next experiment. The fifth disadvantage is the numerous difficulties in combining the standard CMOS technology with the design features of the biosensor.

A known method for increasing the sensitivity of a biosensor (patent application US 20060219939), which presents a method and device for detecting small amounts of bioparticles in small sample volumes. Here, a quadrupole electrode system is used, which contains four electrodes. A drop of the studied suspension is placed between the electrodes. The concentration and manipulation of target particles is carried out using the dielectrophoresis method, which ensures their compression towards the center of the quadrupole system. The method and device also have drawbacks. The first drawback is the four electrodes and the intersection of conductors that supply alternating voltage to them. The second disadvantage is the numerous difficulties in combining the standard CMOS technology with the design features of the biosensor.

A known biosensor is described in the work (Malsagova K.A. Highly sensitive detection of low-copy proteins using a nanowire biosensor. 2019. Dissertation for the degree of candidate of biological sciences., pp. 28-33). The main element of the biosensor is an array of 12 transistors with nanowires. Each transistor has individual source and drain electrodes. The design solution of the topology does not contain and does not provide for the use of electrodes for the purpose of particle manipulation in order to increase the number of particles in the NP region and, thus, increase the sensitivity of the biosensor using dielectrophoresis. As a result, the appearance of the desired viral particle on the surface of the nanowire (gate) is random.

Known biosensor containing an array of nanowires on a crystal and an integrated microfluidic system for supplying biological solutions [Patolsky F., Timko B.R., Zheng G., Lieber C.M. Nanowire - Based Nanoelectronic Devices in the Life Sciences // MRS BULLETIN. 2007 Vol. 32. P. 142-149]. The chip size is 15×15 mm, which is located on the platform and has a liquid inlet channel, a PDMS (polydimethylsiloxane) channel and a liquid outlet channel

However, the analogue biosensor has insufficient sensitivity, because does not have electrodes for manipulation of viral particles by dielectrophoresis in order to increase their concentration in the area of nanowires. The microfluidic system also has typical disadvantages, which are described in detail above (see US patent application US 20040011650).

The closest analogue (prototype) is a biosensor (utility model patent of the Russian Federation No. 178317, IPC G01N 27/414, published on March 29, 2018), made in the form of a field effect transistor for determining biologically active compounds, including a silicon substrate, conductive electrodes, representing the source and drain of the transistor, a sensitive element placed between two conductive electrodes to form a transistor channel, dielectric coatings that provide insulation for the conductive electrodes. The sensitive element is a nanowire made in a thin-film silicon-on-insulator structure formed on a silicon substrate, while gold nanoparticles with a diameter of 2-6 nm are deposited on the surface of the nanowire with a deposition density of 100-7000 pieces/μm ² , on which gold nanoparticles are covalently immobilized fragments of highly specific antibodies to the determined biologically active compound. Conductive electrodes are made of chromium, gold, platinum, aluminium, titanium or heavily doped silicon.

However, the prototype biosensor has insufficient sensitivity due to the lack of means for concentrating particles in the biosensor nanowires and the small number of transistors.

The technical result of the claimed invention is to increase the sensitivity of the biosensor for the indication of viral particles by increasing the number of nanowire transistors and increasing the concentration of viral particles in the area of these nanowires due to the effect on the particles by dielectrophoresis.

This technical result is achieved by the fact that in a biosensor for indicating viral pathogens, including a silicon crystal in the form of a substrate, on which conductive electrodes are located, which are the source and the first drain of the transistor, the sensitive element, which is the first nanowire, is made in a thin-film silicon-on-line structure. - an insulator on a silicon substrate and placed between two conductive source and drain electrodes to form a transistor channel, dielectric coatings providing insulation of conductive electrodes, according to the invention, on the silicon substrate on the other side of the source electrode, symmetrically to the first drain electrode, there is a second drain electrode and a second nanowire, installed between the source electrode and the second drain electrode, and on both sides of one of the nanowires, a pair of lateral electrodes for dielectrophoretic concentration of viral particles are installed, located with a gap relative to the specified nanowire and with axial displacement relative to each other or on both sides of both nanowires, pairs of lateral electrodes for dielectrophoretic concentration of viral particles are installed, located with a gap relative to said nanowires and with axial displacement relative to each other. The axial displacement of the lateral electrodes relative to each other is not more than the width of one lateral electrode.

Dielectrophoresis allows you to control the direction and speed of the translational movement of viral particles using the amplitude-frequency characteristics of an inhomogeneous alternating electric field (NPEP). Under the action of the field, any particle is polarized, and an induced dipole moment is formed in its volume. As a result, it moves towards the nearest electrode and settles on its face (positive dielectrophoresis), or the field pushes the particle into the region where its gradient is minimal (negative dielectrophoresis). Thus, by manipulating particles using the parameters of an inhomogeneous alternating electric field (NIEF), one can purposefully place them on the surface of a nanowire. The implementation of this technical result is achieved by the introduction of lateral electrodes in the area of space covering the nanowire of the transistor and the use of dielectrophoresis.

The inventive biosensor is illustrated by the following graphics. In FIG. Figure 1 shows a biosensor circuit consisting of two SOI-NL transistors, one common source, and one pair of lateral electrodes. In FIG. Figure 2 shows a biosensor circuit consisting of two SOI-NL transistors, one common source, and two pairs of lateral electrodes. In FIG. Figure 3 shows the biosensor circuit, which consists of four SOI-NL transistors, two sources, and two pairs of lateral electrodes. In FIG. 4 shows the calculated structure of the potential of the electric field between two lateral electrodes for dielectrophoresis of the proposed biosensor. In FIG. Figure 5 shows a graph of time currents I _ds of the biosensor measured in air for 1 mM PBS, different voltages V _bg and in samples with different concentrations of 10H10 monoclonal antibodies to tick-borne encephalitis virus. In FIG. 6 shows the electrical circuit of the SOI-NP transistor of the inventive biosensor in the section along A-A in Fig. 1 together with a silicon crystal substrate.

Description of the design of the proposed biosensor. The biosensor for indicating viral pathogens includes a silicon crystal (Si) in the form of a substrate 1, on which conductive electrodes are located, which are the source 2 and the first drain 3 of the transistor, a sensitive element, which is the first nanowire 4 (gate), made in a thin-film structure of silicon- on an insulator on a silicon substrate 1 and placed between two conductive source electrodes 2 and the first drain electrode 3 to form a transistor channel. On the silicon substrate 1, on the other side of the source electrode 2, symmetrically to the first drain electrode 3, there is a second drain electrode 5 and a second nanowire 6 (gate) installed between the source electrode 2 and the second drain electrode 5. On both sides of one of the nanowires 4 or 6, a pair of lateral electrodes 7 and 8 for dielectrophoretic concentration of viral particles located with a gap relative to one of these nanowires 4 or bis axial displacement relative to each other (Fig. 1). In another embodiment of the biosensor (Fig. 2), on both sides of both nanowires 4 and 6, pairs 7, 8 and 9, 10, respectively, of lateral electrodes for dielectrophoretic concentration of viral particles are installed, located with a gap relative to these nanowires 4, 6 and with an axial displacement relative to each other. The axial displacement of the lateral electrodes 7, 8 and 9, 10 relative to each other is not more than the width of one lateral electrode. To provide insulation, the conductive electrodes of the source 2, the first drain electrode 3 and the second drain electrode 5 have a dielectric coating (not shown in the drawings).

The above embodiments of the biosensor (Fig. 1, 2) allow you to create more complex designs of the biosensor from 4, 12, 20, 40 or more SOI-NL transistors. In FIG. Figure 3 shows a biosensor consisting of four SOI-NL transistors and equipped with an additional source electrode. A biosensor for indicating viral pathogens (as in Fig. 1) includes a silicon crystal (Si) in the form of a substrate 1, on which conductive electrodes are located, representing the first source 2 and the first drain 3 of the transistor, a sensitive element, which is the first nanowire 4 (gate) made in a silicon-on-insulator thin-film structure on a silicon substrate 1 and placed between two conductive source electrodes 2 and the first drain electrode 3 to form a transistor channel. On the other side of the source electrode 2, symmetrically to the first drain electrode 3, there is a second drain electrode 5 and a second nanowire 6 (gate) installed between the source electrode 2 and the second drain electrode 5. A pair of lateral electrodes 7 and 8 are installed on both sides of the nanowire 4 for dielectrophoretic concentration viral particles located with a gap relative to the specified nanowire 4 and with axial displacement relative to each other. In addition, conductive electrodes are located on the substrate 1, which are the source 11 and the third drain 12 of the transistor, the third nanowire 13 (gate) placed between the two conductive electrodes of the second source 11 and the third drain 12 to form a transistor channel. On the silicon substrate 1, on the other side of the source electrode 11, symmetrically to the third drain electrode 12, there is a fourth drain electrode 14 and a fourth nanowire 15 (gate) installed between the electrodes of the second source 11 and the fourth drain 14. On both sides of the nanowire 15, a pair of lateral electrodes 16 and 17 for dielectrophoretic concentration of viral particles located with a gap relative to the second nanowire 11 and with axial displacement relative to each other (Fig. 3).

Shown in FIG. 6 is an electrical circuit of the SOI-NP transistor of the inventive biosensor in the section along A-A in Fig. 1, together with the silicon crystal substrate 1, contains an induced conductivity channel 18 (subgate) of the transistor, located under the nanowire 4 (gate) of the transistor and a reference electrode 19. A constant voltage source 20 U=0.15 V is connected in the drain 3-source 2 circuit The plus terminal of the DC voltage source 20 is connected to all drains. A source 21 of constant voltage in the range U=0-30 V (for example, OJ5003CIII) is connected to the gate - ground circuit. Using a universal voltmeter 22 (for example, V7-73/3), included in the DC ammeter mode, measurements were made of I _ds - biosensor current. The test drop of suspension 23 contains virus particles 24 and antibodies 25.

The principle of operation of the biosensor is as follows.

The 0.15 V power supply 20 is connected by a positive terminal to the drain(s) (3, 5, 12, 14) of the transistor(s) through typical pads (not shown in the drawings). The negative terminal of source 20 connected to source(s) (2, 11) is common (ground) for all transistors (biosensors) in the electrical circuit diagram (FIG. 6).

A voltage in the range (0-30) V is applied to the induced conduction channel 18 (sub-gate) of the transistor from the source 21. The voltage is set so that the initial current I _ds of the transistor collector in idle mode is approximately 10 ^-6 A. The initial collector current I _ds the transistor is installed in the complete absence of the test sample (drops 23 of the test suspension).

Next, a drop 23 of a suspension of antibodies 25 with a volume of (0.5-1.0) μl is applied to the surface of the array of transistors. It must necessarily cover the nanowires (4, 6, 13, 15). The transistor current after some time (100-200) seconds is set at the level of the resting state. This level is taken as the reference level. All further measurements of the transistor current Ids are made relative to it. Next, the test suspension is added with a volume of 0.5-1.0 μl. It contains viral particles 24 (antigen). If the antibodies 25 are specific to the introduced viral particles 24, stable antibody + antigen complexes are formed between them. These complexes at the phase separation of the investigated suspension-nanowire surface (4, 6, 13, 15) form an electric charge that modulates the conductivity of the induced channel 18 and, as a result, the transistor drain current changes. The total electric charge of the antibody + antigen complexes reflects the number of viral particles and the amplitude of the change in the current of the transistor as a biosensor. The positive sign of the electric charge of the complexes increases the conductivity of the induced channel 18 and the magnitude of the transistor current. This reaction is determined by the well-known properties of the npn transistor [Dyakonov V.P., Maksimchuk A.A., Remnev A.M., Smerdov V.Yu. Encyclopedia of devices on field-effect transistors / Dyakonov V.P. - M.: SOLON-R, 2002. - 512 p.]. Similarly, the negative charge of the complexes reduces the magnitude and amplitude of the current of the transistor (biosensor).

Lateral electrodes (7, 8, 9, 10, 16, 17) allow you to control the direction of the translational movement of viral particles 24 using the dielectrophoresis method. After the test suspension is added to the surface of the array of transistors and nanowire (4, 6, 13, 15), an alternating voltage is applied to the lateral electrodes (7, 8, 9, 10, 16, 17) for 5-10 seconds. As a result, the concentration of viral particles 24 in the region of the nanowire (4, 6, 13, 15) and at the phase separation of the suspension-nanowire (transistor gate) under study increases, which increases the probability of indicating the desired viral particles 24. The amplitude and frequency of the alternating voltage on the lateral electrodes ( 7, 8, 9, 10, 16, 17) is determined experimentally for each antigen individually.

The time dependence of the current I _ds of the biosensor, measured in air, in samples with different concentrations of tick-borne encephalitis virus is shown in Fig. 5.

An example of the implementation and use of the proposed biosensor.

The experiment used the inventive biosensor manufactured at the Institute of Semiconductor Physics. A.V. Rzhanov of the Siberian Branch of the Russian Academy of Sciences, a fragment of which is shown in Fig. 3 and consisting of 40 field-effect transistors connected to two common electrodes that perform the function of the first and second sources (2, 11), lateral electrodes (7, 8, 16, 17) for manipulating the direction of the forward movement of antigen 24 and antibody 25 particles in the nearest space nanowires 4 or 15, the use of constant voltage sources 20 and 21.

The biosensor crystal in the form of substrate 1 is made on the basis of SOITEC plates (France). The plates had a p-type conductivity and a resistivity of 14-22 Ohm cm.

The external view of the topology of four SOI-NL transistors on two sources 2, 11 with lateral control electrodes (7, 8, 16, 17) is shown in Fig. 3. The electrical circuit of the SOI-NP transistor is shown in Fig. 6. Transistors were made by optical lithography. All transistors had an n-p-n type structure.

An alternating harmonic voltage with a frequency of 1 MHz and an amplitude of U=10 V was applied to the lateral electrodes, without a constant component from the generator G3-112/1 [Technical description and operating instructions G3-112/1]. The frequency was controlled using an ASN-8322 frequency meter. The relative frequency measurement error did not exceed ±10 ^-4 % [User's Guide. Frequency meter ASN-8322]. The voltage was controlled by a V7-78-3 voltmeter. The relative error in measuring the voltage amplitude was no more than ± 0.16% [Operating manual. Universal digital voltmeter V7-78/3.].

вызывает перераспределение (поляризацию) совокупности свободных и связанных, положительных q⁺ и отрицательных q^- зарядов во всем объеме частицы 24 (клетке, вирусе, бактерии и др.). В результате возникает индуцированный диполь

на который действует усредненный по времени вектор силы, см. уравнение (1). Он приводит частицу (клетку, бактерию, вирус и др) в поступательное движение и удерживает ее между латеральными электродами (7, 8) [Hughes М.Р., Morgan Н., Rixon F.J. Dielectrophoretic manipulation and characterization of herpes simplex virus-1 capsids // Eur. Biophys. J. 2001. V. 30, N 4. P. 268-272.].Between lateral electrodes (7, 8) NPEP

causes a redistribution (polarization) of the totality of free and bound, positive q ⁺ and negative q ^- charges in the entire volume of particle 24 (cell, virus, bacteria, etc.). The result is an induced dipole

on which the time-averaged force vector acts, see equation (1). It brings the particle (cell, bacterium, virus, etc.) into translational motion and keeps it between the lateral electrodes (7, 8) [Hughes M.R., Morgan N., Rixon FJ Dielectrophoretic manipulation and characterization of herpes simplex virus-1 capsids // EUR. Biophys. J. 2001. V. 30, N 4. P. 268-272.].

where: ε _cp - dielectric constant of the medium;

ε _cl - dielectric permittivity of the particle (cells, etc.);

- градиент квадрата напряженности электрического поля в среде.

- the gradient of the square of the electric field strength in the medium.

Depending on the sign of the difference ε _cl -ε _av , the force acting on the particle can be either positive or negative. At a frequency of 1 MHz, it is positive. In this case, the particles move to the edge of the electrodes (7, 8) in the area with the maximum gradient of the square of the eclectic field strength and settle on it

градиента напряженности электрического поля между ними по оси симметрии. Расчетная структура потенциала ϕ электрического поля между латеральными электродами для диэлектрофореза представлена на фиг. 4.The shift of the lateral electrodes relative to the axis of symmetry makes it possible to achieve the maximum

electric field strength gradient between them along the axis of symmetry. The calculated structure of the potential ϕ of the electric field between the lateral electrodes for dielectrophoresis is shown in Fig. four.

The values of the strength components E of the electric field between the lateral electrodes are calculated from the coordinates X, Y as the sum of their squares

The desired value of the gradient of the squared strength of the two-dimensional electric field at each point between the lateral electrodes (7, 8) is found by the formula

The results of the indication of antibodies to tick-borne encephalitis 10H10

The experiment used:

- tick-borne encephalitis virus Strain 205 (FBSI SRC VB "Vector of Rospotrebnadzor");

- monoclonal antibodies 10H10 to tick-borne encephalitis virus (FBSI SRC VB "Vector" of Rospotrebnadzor).

Phosphate buffer (PBS) 1 mM was diluted in: Na ₂ HPO ₄ 0.05 M + NaCl 0.15 M, pH8. The studied suspension of 23 purified monoclonal antibodies (MCA) 10H10 to tick-borne encephalitis virus (TBE), strain 205, had a concentration of 1 mg/ml in a solution of 0.15 M NaCl, 0.010 M Trib pH7.4. The MCA suspension was sequentially diluted in 1 mM PBS in the ratios 10H10:PBS=10 ^-1 -10 ^-6 for performing the experiments and applied by drop method (drop volume 1 μl) onto the crystal in the form of a substrate 1 of the biosensor and the surface of the nanowire 4. Concentration of antibodies to the virus EC was ~ 10 ⁶ pcs/µl. In the experiment, the physical fixation of antibodies on the surface of nanowire 4 was used, as it is not expensive and the simplest. For this purpose, the surface of the nanowire 4 was not modified [Nikonov A.M., Naumova O.V., Generalov V.M., Safatov A.S., Fomin B.I. Surface preparation of nanowire silicon field-effect transistors as a stage of biosensor development: a review. Surface. X-ray, synchronous and neutron studies, 2020, No. 4, pp. 24-34.]. Before measurement, an alternating voltage with a frequency of 1 MHz and an amplitude of 10 V is applied to the lateral electrodes (7, 8) for 5 seconds. A field and dielectrophoresis of particles arise between the lateral electrodes (7, 8), which move towards the nearest electrode and settle on it edge and onto the surface of the nanowire 4. Using the voltage of the power source 21 OJ5003CIII, the initial value I _ds of the biosensor current is selected, relative to which the reading is made.

With an increase in the voltage of the power source 21 V _bg current values I _ds increases (see Fig. 5), t - 2500 sec. The positive voltage of the source 21 induces an electronic conduction channel 18 between the source 2 and drain 3 regions of the biosensor. Experimentally, the optimal initial value of the current I _ds was chosen at the level of 10 ^-6 A, which ensures high sensitivity of the biosensor. A decrease in current I _ds at a fixed voltage V _bg and after replacing PBS with a sample with MCA (t=1000-1200) sec means that antibodies to the TBE virus in the samples under study on the surface of the nanowire 4 of the transistor have a negative charge. This conclusion follows from the well-known reaction of a transistor with an npn structure [Dyakonov V.P., Maksimchuk A.A., Remnev A.M., Smerdov V.Yu. Encyclopedia of devices on field-effect transistors / Dyakonov V.P. - M.: SOLON-R, 2002. - 512 p.].

Amplitude changes in biosensor current I _ds as a function of voltage V _bg , and MCA concentration in the sample are shown in Fig. 5, which shows a graph of time currents I _ds of the biosensor, measured in air (t=0-100) sec, for 1 mM PBS (t=100-1200) sec, different voltages V _bg and in samples with different concentrations of monoclonal antibodies 10H10 to tick-borne encephalitis virus (t=1200-2500) sec. At a time interval of 2500 sec, the voltage from source 21 was increased to 20 V to dilute the virus by 10 ^-4 times. From the given data it follows that the response of the biosensor - the relative changes in current I _ds for the sample 10H10:PBS=10 ^-6 is ~ 65%, for a sample with a dilution of 10 ^-5 - 90%. The biosensor practically does not react to a sample of 10 ^-4 - saturation is observed, associated with the absence of free bonds capable of ensuring the adsorption of MCA on the sensor surface, or access to these bonds is blocked.

Thus, an example of the implementation and use of the proposed biosensor confirms the achievement of the claimed technical result, which consists in increasing the sensitivity of the biosensor to indicate viral particles due to their concentration by dielectrophoresis on the surface of the nanowire.

Claims (2)

1. A biosensor for indicating biopathogens, including a silicon crystal in the form of a substrate, on which conductive electrodes are located, which are the source and the first drain of the transistor, a sensitive element, which is the first nanowire, made in a thin-film silicon-on-insulator structure on a silicon substrate and placed between two conductive source and drain electrodes to form a transistor channel, dielectric coatings that provide insulation of conductive electrodes, characterized in that on the silicon substrate on the other side of the source electrode, symmetrically to the first drain electrode, there is a second drain electrode and a second nanowire installed between the source electrode and the second drain electrode, and on both sides of one of the nanowires, a pair of lateral electrodes for dielectrophoretic concentration of viral particles are installed, located with a gap relative to the specified nanowire and with an axial displacement relative to each other or both The crowns of both nanowires are equipped with pairs of lateral electrodes for dielectrophoretic concentration of viral particles, located with a gap relative to these nanowires and with an axial displacement relative to each other. 2. The biosensor according to claim 1, characterized in that the axial displacement of the lateral electrodes relative to each other is not more than the width of one lateral electrode.

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