LT6394B - System and method of analyse of liquid sample - Google Patents

Abstract

Programmable, variable step system for applying a liquid biological solution on a surface of chosen individual array elements of CMUT sensors delivers variable amounts of material for sensor surface modification and for analyses. By changing nozzle of the solution dispensing device, solutions of different material can be applied or concentration of a material changed. The system according to the invention comprises a positioning device of the sample dispensing device, a sample dispensing device with a dispensing nozzle, whose dimensions depend on the liquid volume being dispensed on array elements of the sensor and the position of which is controlled by electric actuator or piezo-actuator. Surface of the CMUT cell array is modified. Afterwards on top of it a sample of a biological liquid solution is dispensed for obtaining the characterizing signal of the sample. CMUT cell sensor arrays are connected in series to the signal processing and measurement device for measuring electromechanical impedance of the CMUT sensor membrane.

Description

Field of the Invention

The invention relates to automated biological sample analysis systems with CMUT sensors and to the use of such systems for liquid biological sample analysis.

State of the art

Microelectromechanical systems (MEMS) devices such as micro / nano clamps, thin film resonators (FBARs), surface acoustic wave (SAW) devices and capacitive micromountable ultrasonic transducers (CMUTs) are used today as resonant, acoustic or gravimetric chemical and biochemical sensors. The CMUT structure is made up of cells, which are capacitors with a single moving plate (membrane) which is aligned with the top electrode, separated from the structural base by a vacuum gap and insulating brackets. The most commonly used is a disk-shaped membrane, but can be rectangular, polygonal, or other. The structure of a single cell is formed on a plate of silicon or other material which also functions as a bottom electrode. Applying voltage to the electrodes, regardless of polarity, the membrane tilts toward the base due to coulomb interaction. The membrane vibration is excited by changing the membrane deflection with an alternating electric field. When the CMUT element is loaded with additional mass, the dynamic cell parameters change: resonant frequency and electromechanical impedance.

CMUT sensors can be manufactured as one-dimensional or two-dimensional arrays composed of cells connected in the appropriate order. Arrays of cells are called elements. The sensor may have one or many elements. With a multi-element sensor, multiple channels can be measured simultaneously, keeping the device small in size. This creates the potential for multi-channel measurements, which is a great advantage when there is a need for a large number of measuring probes in a small sensor area.

For liquid biological assays, the CMUT sensor working surface is modified using molecules that specifically interact with the analyte that selectively binds to the modified surface, thereby allowing for physical, chemical, and / or biochemical changes on the sensor surface. In this way, changes in mass and viscosity can be detected by analyzing changes in resonant frequency, acoustic wave propagation speed and damping. conventionally, liquid materials are deposited on the CMUT sensor by dipping, dripping, centrifuging, spraying and other means. However, all of the above methods are very inaccurate when the sample has to be applied to very small, tens or hundreds of micrometers of CMUT sensor elements.

The closest analogue is disclosed in patent application no. US 12 / 686,916. This application discloses a liquid sample analysis system; it employs a CMUT cell array and a method for analyzing a liquid sample in said system. The CMUT sensor used in the system consists of CMUT cells with a functionalized membrane supported by a support frame over the substrate, thus defining a vacuum cavity under the membrane. By excitation of the transducer with membrane and substrate-matched electrodes, the membrane reaction is detected by electrical capacitance, optical, mechanical stress or other types of detectors. Sensors formed from CMUT cell arrays are separated from each other by mechanical barriers to avoid interference of measurement signals between CMUT arrays. The method of testing liquid samples using the disclosed system includes applying a liquid sample to a CMUT device by dipping the CMUT device into a liquid sample, drying the CMUT device, electro-mechanically detecting the dried material on the CMUT device, and determining the mass of that material. A major disadvantage of the present invention is that the liquid sample is deposited onto all elements of the CMUT array of the analyzing system simultaneously. This does not provide a channel for analysis and comparison of biological samples. Comparison is only possible when testing with another converter or after cleaning the converter, which increases measurement uncertainty due to different measurement conditions. Another disadvantage is that the invention disclosing an analogue does not provide for sensor selectivity between membrane-bound and non-specifically bound substances. Therefore, the use of such a liquid sample analysis system is severely limited in terms of the information received.

The present invention solves the problem of accurately depositing liquid materials on CMUT cell array based liquid biological assay systems with CMUT sensors on individual array elements. This allows you to have more than one measuring channel and analyze different biological samples or different concentrations at the same time. Also, our invention improves the controllability and repeatability of the fluid application on CMUT sensor array in terms of both the volume of liquid applied and the area of the liquid covered CMUT sensor. This allows for much more sophisticated measurement algorithms, such as a series of different fluid application, drying, and washing steps, such as antigen modification, water washing, antibody loading, water washing, drying, and measurement. This reduces measurement uncertainty, and increases the sensitivity of the sensor signal, for example, by detecting specific and non-specific interactions of the analyte with the membrane.

Brief Description of the Invention

A programmable, variable-step application system of liquid biological solutions on the surface of individual arrays of selected CMUT sensors can carry varying amounts of sensor element modifying material and analyte. Changing the ejector nozzle may result in solutions of different materials or changes in the concentration of the materials. The solution delivery system includes a sample ejector positioning device with a liquid dosing ejector with a dosing nozzle, the dimensions of which depend on the volume of liquid applied to the array elements of the CMUT sensor, and is controlled by an electric or piezoelectric actuator. The surface of the CMUT cell array is modified, for example, by immobilizing on it an active biochemical element, such as an antigen, and a sample of a liquid biological solution, such as an antibody, is deposited on it to produce a signal characterizing the sample. The CMUT sensor cell arrays are sequentially connected to a signal measuring and processing device that measures the electromechanical impedance of the CMUT sensor membranes, which is directly related to the physical properties of the resulting coating solution, such as the Jungian modulus, viscosity, density. A computer device is used to store and process data. Prior to measurements, the surface of the CMUT sensor membranes is modified by applying a precise dose of modifying fluid to each element of the CMUT sensor array, which is controlled by varying the ejector movement velocity, tip tip distance, sensor surface material, sensor cell arrays. separating by hydrophobic barriers. Thereafter, the interaction of the precipitated liquid biological sample with specific analyte molecules on the intended CMUT sensor membrane surfaces is investigated by applying an accurate dose of the analyte that is controlled by the ejector speed, tip tip distance, sensor surface material, sensor array elements. others were separated by hydrophobic barriers.

Brief description of the drawings

Other features and advantages of the invention are described in the detailed description of the invention with reference to the drawings below. The accompanying drawings are an integral part of the invention. Drawings and diagrams may not necessarily be scalable. Details that are not necessary for an understanding of the meaning of the act and have no relation to this description are provided.

Fig. 1 is a diagram illustrating the operation of a CMUT sensor cell;

Fig. 2 shows a CMUT sensor divided into separate CMUT sensor arrays, which are separated by hydrophobic barriers;

Fig. Fig. 3a is a view showing one element of a CMUT sensor array, an ejector nozzle with an extruded half-spherical fluid volume;

Fig. Figure 3b shows one element of a CMUT sensor array, an ejector nozzle with an extruded spherical fluid volume;

Fig. Fig. 4 shows an algorithm for measuring a applied liquid biological sample;

Fig. 5 is a schematic diagram of a measuring system;

Fig. 6 is a schematic diagram of a programmable automated, variable step solution application system.

Before referring to the detailed description of the invention, with reference to the drawings of exemplary embodiments of the invention, it is to be noted that identical elements are denoted by the same numerals throughout the drawings.

Detailed Description of the Invention

According to the present invention there is disclosed a CMUT sensor for liquid biological sample assays, a precise surface modification of sensor elements and an accurate deposition of liquid biological solution samples using a system with CMUT sensors.

The CMUT sensor (201, 304) comprises at least one array element (202) comprising at least one cell (101) having a diameter of, for example, 10 to 100 µm. Preferably, the number of cells per cell (202) is more than one. At least one cell (101) comprises a membrane (102) which is separated from the structural substrate (104) by insulating brackets (103) to form a vacuum gap (105). The membrane top layer (106) is made of a material, such as gold, on which a technologically active layer (107) can be formed for modification of the transducer membrane. The membrane shape may include, but is not limited to, disk-shaped, quadrangular, polygonal, or other forms. At least one membrane layer (102) is electrically conductive and serves as a top electrode (106). An insulating layer (103) is formed between the diaphragm (102) and the substrate (104), for electrode separation and a vacuum gasket (105) for vibration of the diaphragm. The sensor cells (101) are formed on a doped silicon wafer (104) which serves as a lower electrode. A voltage is applied to the sensor electrodes (104, 106) regardless of polarity. The membrane (102) is inclined towards the base due to the coulomb interaction, and the vibration of the membrane is induced by changing the membrane deflection by an alternating electric field. To increase mechanical power and electrical impedance components, CMUT cells (101) are connected in parallel to form arrays of sensor (201) elements (202) comprising one or more cells (101). The vibration frequency of the CMUT cell, depending on the membrane design and the functional materials, covers the 100 kHz + 60 MHz band. When the CMUT array is loaded with additional mass, the dynamic sensor parameters change: resonant frequency and electromechanical impedance. In order for the CMUT sensor (201) to function as a chemical and / or biological sensor, the surface of its cells (101) is modified, i.e., coated with an active substance layer (107) that interacts with the liquid constituents to be analyzed. As a result of the resulting connections with the constituents of the material being analyzed, the mass and viscoelastic properties of the vibrating membrane are altered, while altering the resonant frequency, oscillation amplitude and resonance quality of the system. This type of CMUT sensors exhibit high sensitivity (up to 10 ^'15 g) to changes in membrane mass. Further, the transducer elements are further separated by hydrophobic baffles (203) for surface modification of the sensor elements (202) for surface modification and analysis of the liquid material for sensing the liquid material by the sensor (201), and for preventing the transfer of liquid material to the adjacent transducer element. ). Hydrophobic partitions may be formed from ultraviolet polymeric material such as SU8, EpoCore, EpoClad and others, or hydrophobic PECVD silicon nitride.

The process of analyzing a liquid sample, such as a liquid biological sample such as human or animal blood plasma, a preparation thereof, or another natural biological fluid preparation, begins by modifying the surface of at least one array element (202, 303) of said at least one CMUT sensor (201). (401). This is accomplished by depositing a solution (205) containing the surface modification molecules (108) on the surface of the sensor element (202, 303). Surface modification involves different immobilization techniques (402) depending on the surface layer (gold, silicon nitride, etc.), and one of these (without prejudice to the use of other appropriate immobilization methods) is the binding of solution molecules to the membrane surface by glutaric aldehyde vapor. Following this procedure, the membrane is washed and dried (402) if assayed in air, or after washing, left in solution if interaction with the analyte is recorded in a liquid medium. Non-specific surface-immobilizing substances are removed during washing. The substances in the solution are immobilized (402) on the surface of the sensor (201) elements (202, 303) using additional physical and / or chemical processes, such as drying, bifunctional reagent vapor or solution binding. Excess immobilizers are removed from the surface by washing.

The amount of active modifying solution is applied to the surface of the sensor element (202) by means of an ejector (204, 301, 30T, 614), which is mounted in a holder (618) controlled by electric actuators (601, 604, 608, 611). The movement of the ejector is controlled by programmable actuators (501, 601, 604, 608, 611) via a computer tool (506). The application of the solution is accomplished by contacting the ejector nozzle by touching an amount of solution which, due to the surface tension of the liquid, is limited to the diameter of the nozzle and forms an approximately half-spherical derivative (205, 302). The volume of the ejected solution in this form can be controlled by changing the ejector nozzle parameters. In one case, a hydrophobic ejector nozzle (204, 301) of appropriate diameter is used to ensure a minimum volume of squeezable solution, thereby forming a semi-spherical water derivative on the end of the ejector nozzle (204, 301). For example, using a needle made of a hydrophobic material with an outer diameter of 0.8 mm and an inner hole of 0.4 mm, it is possible to form a 0.4 mm diameter half-spherical drop (205, 302). By vertically positioning the ejector nozzle with a 0.4 mm diameter half-sphere drop to within 1 micrometer of the surface of the CMUT sensor array element (202, 303), the water-capable fluid can modify the sensor element (202, 303) or more. By reducing the diameter of the needle hole to 0.2 mm, a half-sphere drop can be used to modify the sensor element (202, 303) or larger by 56 µm in diameter. Alternatively, using a ejector nozzle, for example, a medical needle (301 ') of hydrophilic material having an outer diameter of 0.8 mm and an inner diameter of 0.4 mm can be used to form a half spherical drop (302'). By positioning the ejector tip with a 0.8 mm diameter half-sphere drop vertically within 1 micrometer of the surface of the CMUT sensor element (202, 303), the water-like fluid can be modified with a 160 micrometer diameter or larger sensor element by reducing the needle diameter to 0.4 mm, respectively. a sensor element (202, 303) 80 microns in diameter or larger can be modified. The needle of said dimensions forms a sphere of water of at least 1 mm in diameter, the deposition of which, for example by dripping, would wet a much larger area of the sensor.

The ejector nozzle (204, 301) of each element (202, 303) is brought to the sensor (201, 304) such that the formed liquid derivative (205, 302) contacts the surface of the CMUT transducer element (202, 303). The volume of fluid deposited may additionally be controlled by controlling the contact time of the fluid surface (202, 303) with the surface of the CMUT element by synchronizing the ejector piston retraction with the ejector itself. The volume so deposited is less dependent on the diameter of the ejector nozzle. By controlling the duration of the touch, it is possible to personalize each sensor element during its use (no need to change design or photo templates), apply different amounts and volumes of analyte on freely selected transducer elements, thus forming support channels and channels for exploration of material interaction parameters. Due to the limited velocity of the fluid in the hydrophilic area of the sensor element, a shorter contact time means a smaller amount of the deposited liquid and vice versa. In practice, the minimum deposited volume is limited to a minimum contact time of about 10 ms. Liquid deposition in short touches, the duration of which is caused by the small dimensions of the sensor elements and (as a consequence) by the small volume of liquid deposited, can significantly increase the rate of modification of the entire sensor. The shortest practical placement of the ejector nozzle in the x-y axis is about 50 ms, while the z-axis has a total mounting and contact cycle of 30 ms. This saves about ms for one element modification, which represents a maximum modification performance of 12.5 arrays of elements (202, 303) per second.

After the modification step, supporting measurements (403) are performed to evaluate the resonant frequency, oscillation amplitude and resonance quality changed after the CMUT sensor surface modification. This is important in determining the selective response of a sensor to non-specific and membrane-interacting molecules.

A modified sensor surface (108) is provided with a solution containing the analyte (109), whose interaction at the transducer (101) surface (108) is recorded (404). The interaction of the analyte with the CMUT transducer membranes (405) can be controlled by maintaining the temperature, using catalysts, measuring and controlling the interaction time, or other similar means.

The amount of analyte solution is applied to the surface of the transducer (201, 304) element (202, 303) by means of an ejector, which is mounted in a holder (618) controlled by electric actuators (601, 604, 608, 611). The movement of the ejector is controlled by programmable actuators (501, 601, 604, 608, 611) via a computer tool (506). Applying the solution is done by touch. On the ejector nozzle (204, 301), an amount of solution is extruded which, due to the superficial stresses of the liquid, is limited to the diameter of the nozzle and forms an approximately half-spherical derivative (205, 302). The volume of the ejected solution in this form can be controlled by changing the ejector nozzle parameters. In one embodiment, a hydrophobic ejector nozzle (301) of appropriate diameter is used to provide a minimum spherical volume of solution, thereby forming a half-spherical solution derivative (302) on the end of the ejector nozzle. For example, using a needle made of a hydrophobic material having an outer diameter of 0.8 mm and an inner hole of 0.4 mm, it is possible to form a 0.4 mm diameter half-spherical drop (302). By positioning the ejector tip with a 0.4 mm diameter half-sphere drop vertically within 1 micrometer of the CMUT element surface, a water-soluble fluid can modify the sensor array element (202, 303) 80 microns in diameter or larger by reducing the needle hole diameter to 0.2 mm, a sensor array element (202, 303) having a diameter of 56 micrometers or larger can be modified accordingly. Alternatively, using a ejector nozzle, for example, a medical needle (30T) of hydrophilic material having an outer diameter of 0.8 mm and an inner diameter of 0.4 mm, it is possible to form a half spherical drop (302 ') covering the entire end of the ejector nozzle. perimeter. By positioning the ejector tip with a 0.8 mm diameter half-sphere drop vertically to within 1 micrometer of the CMUT element surface (303), the water-like fluid can be modified with a 160 micrometer-diameter or larger sensor element by reducing the needle diameter to 0.4 mm, micrometer diameter or larger sensor element. The needle of said dimensions forms a sphere of water of at least 1 mm in diameter, the deposition of which, for example by dripping, would wet a much larger area of the sensor.

The ejector nozzle (301) of each element (303) is led to the transducer (304) such that the formed liquid derivative (302) contacts the surface of the CMUT element. The volume of deposited fluid may additionally be controlled by controlling the contact time of the fluid surface (302) with the surface of the CMUT element (303) by synchronizing the ejector piston retraction with the ejector itself. The volume so deposited is less dependent on the diameter of the ejector nozzle. By controlling the touch duration, each element of the sensor array (303) can be personalized during use (no need to change design or photo templates), different amounts and volumes of analyte can be deposited on freely selected transducer elements, thereby forming support channels and channels for scattering response . Because of the limited velocity of the fluid to pass through the hydrophilic area of the sensor element, a shorter contact time means less amount of fluid deposited and vice versa. In practice, the minimum deposited volume is limited to a minimum contact time of about 10 ms. Liquid deposition in short touches, the duration of which is due to the small size of the sensor elements and (as a consequence) the small volume of liquid deposited, can significantly increase the rate of modification of the entire sensor. In practice, the shortest placement of the ejector nozzle in the x-y axis is about 50 ms, while the z-axis has a total mounting and touch cycle of 30 ms. This takes about 80 ms to modify one element, which means a maximum modification performance of 12.5 elements per second.

Unnecessary reaction products and unmobilized materials may be removed by washing (406) or other means prior to measurements (408). The resulting structure on the surface of sensor cell arrays may be further washed, dried, or otherwise treated prior to measurement (407). The measurements (408) comprise at least measurements of the electromechanical impedance parameters, the measurement data being stored in a data storage medium of a computer device connected to the measuring device. After a complete measurement cycle, the surface of the converter (202, 303) can be cleaned (409), ready for a new measurement.

In addition to the above-mentioned means for achieving controlled volume deposition of the liquid modifier and the analyte solution on the CMUT sensor element (202, 303), additional hydrophobic barriers (203) are used to limit the area of the individual CMUT sensor array elements (202, 303). The area of the hydrophilic material (such as gold) (working area of the sensor element) can be formed on the CMUT transducer element using direct or reverse photolithography technique. The area of the hydrophilic material may be limited to a hydrophobic material (such as a photopolymer or silicon nitride). In order to cover the entire hydrophilic area of the sensor element (202, 303) (which may be smaller than the diameter of the droplet formed by the ejector nozzle), it is sufficient to touch the hydrophilic surface with the edge of the fluid sphere (205, 302) at a point. The hydrophilic interaction between the surface of the liquid and the surface of the sensor will break the barrier formed by the surface forces of the liquid, and a portion of the formed drop will be dispersed on the surface of the sensor. At the same time, the hydrophobic material limiting the working surface of the sensor element (202) will prevent the fluid from spreading over a larger area, and the amount of fluid deposited will be proportional to the dimensions of the working surface of the sensor element and hydrophilicity. This will result in greater accuracy and repeatability of sensor modification.

The described fluid deposition technique allows the liquid to be deposited in a much smaller area than other known liquid deposition methods by using an ejector nozzle of conventional dimensions and materials. A smaller deposition area means smaller dimensions of the sensor array elements, which also means a smaller overall sensor dimension. Because CMUT sensor cells are manufactured using silicon micromachining technology, their production cost is determined by the area of the crystal occupied. The smaller the sensor, the cheaper it is. On the other hand, the deposition area can be reduced without reducing the size of the ejector nozzle.

The device used for surface modification of the elements of the CMUT sensor (201, 304, 615) and for analyzing the analyte solution comprises at least a frame structure (607, 617), a computer controlled x-axis (601), a y-axis (604), metering up / down (608). and actuator piston control (611) actuator, ejector holder (613). With these actuators and with the help of the guides (602, 603, 605, 606, 609, 610) the displacement of the dispenser (613) is controlled in the x and y axis directions. The metering unit is raised or lowered in the Z axis. The computer-controlled displacement of the dispensing plunger (612) ensures accurate squeezing of the solution on the tip of the ejector nozzle and subsequent application thereof to the array element (202, 303) of the selected CMUT sensor (615). The CMUT sensor is attached to the table (616) by means of a vacuum suction cup.

A circuit analyzer or a specialized electronics unit (504) is used to measure the amplitude and frequency of the electromechanical impedance. The change in both parameters is measured at the same time, so that all information collected during the measurement is potentially more reliable and better illustrated than by performing one of the selected parameters, e.g. resonant frequency measurements. The electronics unit used has one measuring channel. The individual CMUT element arrays (202, 303) (measurement channels) are connected to the electronics unit (504) via a switch (503). The circuit analyzer (504) and the solution applicator (501) are controlled by computer means (506). A computer tool is also used to collect, store, interpret, and process information from the measurement process. Additional means (washing, drying, etc.) are used to immobilize reagents on the surface of the transducer, to control the reaction process, and to remove unnecessary reaction products (505).

Although the practice of the present invention is particularly suitable for the analysis of soluble biological material solutions, it should be understood that the present invention can be applied to the analysis of both liquid, gaseous and solid materials.

Claims (13)

Definition of the Invention A liquid sample analysis system comprising a CMUT sensor, a fluid carrier, a computer controlled ejector positioning device, wherein the CMUT sensor (201, 304, 615) elements (202, 303) are within a micrometer diameter range, the CMUT sensor elements ( 202, 303) are separated from one another by hydrophobic baffles (203), and in that the ejector nozzle positioning device comprises guides (602, 603; 605, 606; 60, 610) for positioning the ejector holder (613). 2. A system according to claim 1, characterized in that the elements (202, 303) of the CMUT sensor (201, 304, 615) are in the range of tens to hundreds of micrometers in diameter. 3. The system of claim 1, wherein the ejector nozzle (301) is hydrophobic. 4. The system of claim 1, wherein the ejector nozzle (30T) is hydrophilic. A method of depositing liquid materials using a liquid sample analysis system with a CMUT sensor according to any one of claims 1 to 4, comprising modifying the surface of the CMUT sensor, applying a liquid sample to the CMUT sensor, drying the CMUT sensor, electrical detection of the material dried on the sensor. and determining the weight of the dried material, wherein the surface modification of the CMUT sensor array arrays is performed automatically, wherein the volume of the surface-deposited modification fluid of each CMUT sensor element (202, 303) is controlled; the liquid assay sample on the optional individual CMUT sensor element (202, 303) is deposited by touching the liquid assay sample onto the sensor element (202, 303) and the volume of the liquid sample deposition on the CMUT sensor element is controlled; and further comprising controlling the electromechanical impedance of the CMUT sensor elements (202, 303) after surface modification and after accurately depositing the liquid sample onto the surface of a freely selected CMUT element, controlling the interaction of the liquid sample with CMUT cell membranes (102). 6. The method of claim 5, wherein the automatic surface modification of the CMUT sensor array arrays comprises ejecting a precise volume of liquid material simultaneously and individually on each modifier (202, 303), wherein said plurality is effected by contacting the volume of the liquid separately with the CMUT. the surface of at least one element (202, 303) of the sensor, and wherein the minimum contact surface area is not greater than the area of one element (202, 303) of the CMUT sensor. 7. The method of claim 5, wherein the automatic surface modification of the array of CMUT sensor elements comprises ejecting a precise volume of liquid material in a sequential manner and individually on each modifiable element (202, 303), wherein said plurality is performed by contacting the liquid volume separately with the CMUT sensor. at least one surface of the element (202, 303), and wherein the minimum contact surface area is not greater than the area of one element (202, 303) of the CMUT sensor. 8. A method as claimed in any one of claims 5 to 7, wherein the volume of modifying fluid to be deposited on the surface of each element (202, 303) of the CMUT sensor is controlled by at least actuating actuators (601, 604, 608, 611) and / or separating the CMUT sensor elements (202, 303) and / or each other by barriers (203) and / or changing the surface wetting angle by changing the surface materials of the sensor elements (202, 303). 9. The method of claim 5, wherein the touch-deposited accurate dose of the liquid sample on each optional individual element (202, 303) of the CMUT sensor is deposited on a surface of no more than a single touch surface (202, 303) of the CMUT sensor. Method according to claim 5 or 9, characterized in that the volume of the liquid sample deposited on the surface of each element (202, 303) of the CMUT sensor is controlled by controlling at least ejector actuators (601, 604, 608, 611) and / or the CMUT sensor. separating the elements (202, 303) and / or from each other by barriers (203) and / or changing the surface wetting angle by changing the surface materials of the sensor elements (202, 303). 11. The method of claim 5, wherein, after accurately depositing the liquid sample onto the surface of a freely selected CMUT element, controlling the interaction of the liquid sample with CMUT cell membranes (102) comprises at least maintaining temperature and / or using a catalyst and / or measuring the interaction time. and management. A method according to any one of claims 5 to 11, characterized in that a liquid sphere derivative (302, 302 ') is formed on the ejector nozzle to deposit the liquid material on the CMUT sensor elements (202, 303). 13. A method as claimed in any one of claims 5 to 12, wherein the contact time of the deposited liquid material on the surface of the CMUT sensor element is about 10 ms.