RU2383004C2 - Bifunctional acoustooptical sensor for physical-chemical and medical-biological research of nanofilms - Google Patents

Abstract

FIELD: measurement equipment.

SUBSTANCE: invention is related to the field of measurement equipment, in particular to microelectronic sensors - chemical and biosensors, which are intended for simultaneous acoustic (on surface-acoustic waves (SAW)) and optical investigations of physical-chemical and (or) medical-biological properties of fine nanofilms of around 0.1 mcm (100 nm) and below. Sensor uses light of visible range, for which absorption coefficient are 2-4 orders more than in infrared range, waveguide mode of measurement, in which single crystal of piezoelectric cell is used as flat waveguide for light of visible range, besides two modes of optical waveguide measurements are available: MNPVO or multiple reflecting-absorbing one, and also heater in the form of several chip-resistors, which are connected into serial circuit, and temperature detector - platinum resistance thermometre.

EFFECT: improved sensitivity and simplified design.

4 dwg, 1 tbl

Description

The present invention relates to the field of measurement technology, in particular to microelectronic sensors - chemical and biosensors, designed for simultaneous acoustic and optical studies of physico-chemical and (or) biomedical properties of thin order of 0.1 microns (100 nm) nanofilms.

Microelectronic sensors - sensors, with the help of which it is possible to carry out simultaneous measurements of two or more physical parameters of the same micro-object in one physicochemical and (or) biological process, have recently received a special name - “Lab on Chip” (Lab on Chip) ) A feature of these measuring microcells is that they are made using the technologies of micro- and nanoelectronics, in particular micro- and nanoelectronics. Thin nanofilms, multi- and monolayers of artificial (polymers, dielectrics, semiconductors) and natural origin (natural polymers, proteins, sugars, enzymes) are the objects of research. Studies are conducted at the level of recognition of individual abnormal mutations against the background of the right ones [Th. M.A. Gronewold, A. Baumgartner, E. Quandt, M. Mamulok. Discrimination of Single Mutations in Cancer-Related Gene Fragments with a Surface Acoustic Wave Sensor // Anal. Chem. 2006. V.78. Number 14. P.4865-4871]. To study the structure of water bound by a protein molecule, a sensor type measuring cell was used, in which measurements were simultaneously performed by quartz microweighting (QCM) and two optical methods: ellipsometry and surface plasmon resonance (SPR) [Hook F., Kasemo B., Nylander T. et al. Variation in coupled water, viscoelastic properties, and film thickness of a mefp-1 protein film during adsorption and cross-linking: a QCM with dissipation monitoring, ellipsometry, and surface plasmon resonance study // Anal. Chem. 2001. V.73. Number 24. P.5796-5804]. To study the nanofilms of the thermosensitive polymer poly- (N-isopropylacrylamide), a combination of surface acoustic wave (SAW) and SPR was used, which allowed very precise control of changes in the viscosity, density and thickness of the films in the temperature range of 20-45 ° С [Francis L., Friedt JM., Zhou S., Bertrand P. In situ evaluation of density, viscosity, and thickness of adsorbed soft layers by combined surface acoustic wave and surface plasmon resonance // Anal. Chem. 2006. V.78. No. 12. P.4200-4209].

On the one hand, Lab on Chip are used for purely research purposes (Research), because have a set of properties that are not available for conventional instruments and measuring macrocells. On the other hand, so-called biomedical cartridges are designed (Development) for mass analysis of fluids and tissues of humans and animals with the goals of: 1) early diagnosis of cancer and other diseases and 2) monitoring the progress of drug treatment. There is already a nanoindustry industry in the world that produces such measuring cells, components for them and devices based on both of the above types (R&D). Leaders: in Europe: Switzerland, Germany, Sweden, Denmark, Netherlands, England; In Asia: Japan, Taiwan. In America: USA, Canada, Brazil. In Russia, to date, this part of the nanoindustry is practically absent. Separate developments are available at Moscow State University, Zelenograd, Pushchino (Moscow Region), St. Petersburg (Ioffe Physical Technical Institute, Institute of Physiology RAS), Yekaterinburg, and the SB RAS (Novosibirsk).

The use of such measuring microcells in comparison with traditional devices for physical and physicochemical (biomedical) research has several advantages: 1. the ability to work with micro- and nanosamples in the form of nanofilms and microvolumes of liquids; 2. most often, the lack of preliminary sample preparation; 3. very short time of a single analysis (analysis of one sample), which gives a decisive advantage in the performance of analyzes per unit time; 4. portability; 5. low power consumption and material consumption; 6. the manufacture of a multisensor and the main structural components of the device based on it using microelectronics technologies provides another advantage - relative cheapness; 7. a high degree of automation of analysis does not require a highly qualified operator; 8. if one of the types of surface acoustic waves is used in the sensor, it is possible to perform it in a remote wireless version with the transmission of an analytical signal in the radio frequency range from several hundred MHz to 2-3 GHz at distances from several meters to several hundred meters [Benes E. , Groschl. M., Seifert F., Pohl A. Comparison between B AW and SAW sensor principles // 1997 IEEE International Frequency Control Symposium. P.5-20].

For the first time, a chemical sensor based on surface acoustic waves (SAW) was proposed as a gravimetric sensor for studying the sorption of gases - vapors of organic substances by thin films of polymers in 1997 [Liron Z., Kaushansky N., Frishman G., Kaplan D., Greenblatt J The Polymer-coated SAW sensor as a gravimetric sensor // Anal. Chem. 1997. V.69. Number 14. P.2848-2854]. Already in this work, in which the results of sorption measurements using a traditional measuring cell in a Perkin Elmer - TGA-7 Thermogravimetric analyser device were compared with the results of sorption measurements using a SAW chemical sensor, it was shown that, firstly, the sensitivity of the quantity measurements the adsorbed substance from the vapor phase is higher in the case of the SAW sensor, and secondly, the SAW sensor is significantly superior to the thermogravimetric device in terms of information content: if the latter gives data only on the change in the film mass as a result of sorption , The SAW sensor provides data not only to change the weight of the film, but also to change the constants of visco-elastic polymer film, as a result of advancing sorption. In this work, as a SAW sensor, a widely-known design “SAW delay line” with a resonant frequency of 104 MHz was used; as usual, the studied polymer films were deposited on the surface of a quartz single crystal into the space between interdigital transducers (IDTs).

In 1999, a work was published that described a measuring cell - a chemical multisensor, which is a single crystal of a piezoelectric quartz, on the surface of which five delay lines are formed on surfactants, in which the thinnest about 50 nm gold films are deposited in the space between the IDTs, on which gold films are deposited test films; a channel has been made in the volume of the single crystal, which has an input and an output on one of the end faces of the crystal, i.e. a piezoelectric single crystal is used as a liquid thermostat to set and maintain the temperature of the studied film samples. [Hierlemann A., Ricco A.J., Bodenhofer K., Gopel W. Effective use of molecular recognition in gas sensing: results from acoustic wave and in situ FT-IR measurements // Analitycal Chemistry. 1999. V.71. No. 15. P.3022-3035. International Journal of the American Chemical Society (ACS)]. In this work, the sensor was used to study the sorption of gases and vapors of organic compounds by thin nanofilms of various polymers, natural and modified natural polymers, polycrystalline films of macroheterocyclic compounds, chelate metal complexes. In contrast to the previous cited work, in this work, in addition to measuring the SAW frequency of the samples during sorption, infrared spectra with Fourier transform (FT-IR) films were measured in reflective-absorbing mode, in which a thin beam of infrared light incident on the surface of the studied film at a certain angle, the film passes, falls onto the interface of the studied film / gold film, is reflected from the surface of the gold film, passes through the studied film again and goes to the interface of the studied film and / atmosphere, going on a photodetector. Thus, synchronously (simultaneously), sorption isotherms were obtained from measurements on surfactants, and data on those molecular groups that interacted with adsorbate gas molecules were obtained from FT-IR. These molecular groups are the centers of sorption. Further, the same authors used the sensor described above to study the sorption of vapors of organic compounds by films of polymers of the siloxane series, obtaining sorption isotherms in the temperature range from 0 to 70 ° C through 10 ° C. From the obtained data, all the thermodynamic parameters of sorption were calculated: Gibbs energy, enthalpy, and entropy [Hierlemann A., Ricco AJ, Bodenhofer K., Dominik A., Gopel W. Conferring selectivity to chemical sensors via polymer side-chain selection: thermodynamics of vapor sorption by a set of polysiloxanes on thickness-shear mode resonators // Analitycal Chemistry. 2000. V.72. No. 16. P.3696-3708].

The design of the bifunctional acousto-optical chemical sensor (device) described above is closest to the proposed invention by purpose and technical essence, therefore it is selected as a prototype and will be called a known device in the future. The disadvantages of the known device designed for physico-chemical and (or) biomedical research of nanofilms of substances, in particular studies of the process of sorption of gases and vapors by nanofilms of substances, are the following: 1) low sensitivity of the IR spectra associated with low absorption coefficients in IR -region of substances, which does not allow to obtain quantitative characteristics of the process of sorption of gases and vapors by nanofilms in the region of low concentrations (low partial pressures) of the latter, in comparison with the sensitivity of measurements on surfactants; 2) the low sensitivity of the IR spectra associated with the use of measurements only in a single absorption-reflective mode, in which a light beam passes the studied film only two times in thickness; 3) the high construction cost associated with the extreme complexity of manufacturing capacitor channels in a piezoelectric single crystal, which is used as a liquid thermostat; 4) the accuracy of setting the temperature in a liquid thermostat is not high enough, which is limited by an accuracy of 0.02 ° C; 5) the impossibility of obtaining thermodynamic sorption data from optical IR measurements, which does not allow us to distinguish the contributions to the thermodynamic parameters due to physical sorption and chemisorption; 6) technological difficulties and the high cost of performing a sensor, which does not allow switching from a laboratory version to an industrial mass production of sensors in the form of cartridges and (or) devices based on them, intended for mass use in physicochemical and biomedical applications, not only in research laboratories, as well as in laboratories of hospital and pharmaceutical enterprises. The latter was the reason that the authors of the known device did not patent it, but published its design in a scientific journal.

The purpose of the invention is to develop a device - a bifunctional acousto-optical sensor, its design, in which 1) the sensitivity of the optical measurements will be close to (or even comparable to) the sensitivity (s) of the acoustic measurements, which will allow to obtain data of synchronous acoustic and optical measurements in the region of positive temperatures by which, in particular, it will be possible to construct sorption isotherms, including the region of low concentrations of gases (vapors), to calculate all the thermodynamic parameters of the sorption process, cf VNITI data calculated from both types of measurements, and to allocate contributions to thermodynamic parameters resulting from physisorption and chemisorption; 2) on the one hand, the design of the heating element will be simplified, and on the other hand, the accuracy of setting and maintaining the working temperature of film samples will be increased; 3) the possibility of manufacturing a relatively cheap sensor using the mass technology of micro- and nanoelectronics arising from the second.

The problems solved by the invention are: 1) to provide an increase in the sensitivity of optical measurements to a level close to the sensitivity of acoustic measurements; 2) to simplify the design of the heating element while improving the accuracy of the task and maintaining the temperature of nanofilm samples; 3) to provide the possibility of simultaneously conducting acoustic surfactants and no less sensitive optical measurements of nanofilm samples in one experiment; 4) to simplify and significantly reduce the cost of the sensor design, which will allow, firstly, to switch to the industrial production of sensors using mass technology of micro- and nanoelectronics, and secondly, to create a measuring device based on it, affordable and easy to use not only Researchers, but also the laboratory staff of medical and pharmaceutical enterprises and institutions (hospitals, clinics, diagnostic laboratories, pharmacies, etc.).

The stated goal and objectives are solved: the first task of increasing the sensitivity of optical measurements to a level close to the sensitivity of acoustic measurements, is solved by the fact that in the known device, firstly, instead of infrared light, visible light is used, which is characterized by absorption coefficients 2-4 orders of magnitude greater than in the IR range, and secondly, instead of a single absorption-reflective mode of measuring light by a sample, in which the IR light beam only passes the film twice in thickness, and a waveguide measurement mode is used, in which a quartz single crystal is a piezoelectric, on one of the front faces of which an IDT is formed, which has excellent transmittance in the visible light region, is used as a planar waveguide for visible light (Fig. 1), and light that propagates along the waveguide, depending on the angle of incidence of light on the end face of a single crystal of a piezoelectric, as well as on the ratio of the coefficients (indices) of refraction of materials of a piezoelectric and trick nanoplenki, probes nanofilm along its surface or in a mode of multiple frustrated total internal reflection (ATR) mode or the multiple reflection-absorbances at which the light beam repeatedly penetrate into the film in its entire thickness (Figure 2); The 2nd task of simplifying the design of the heating element while increasing the accuracy of setting and maintaining the temperature of nanofilm samples is solved by the fact that in the known device, in which the piezoelectric single crystal itself is used as a heating element, in which a channel through which the channel was made using sophisticated laboratory technology thermostatic fluid is passed, several CHIP resistors are located and fixed using heat-resistant glue on the front face (each nominal resistance of 500 ohms) connected via microsoldering and connecting conductors in a daisy chain, forming a heater operating at Joule heat that is generated in this heater by passing electric current therethrough; a heater consisting of several chip resistors located symmetrically relative to the center of the single crystal with a total resistance of several kOhm provides fast - within a few seconds - heating of the piezoelectric single crystal and nanofilm to any temperature in the range of 20-70 ° C, depending on the value of the applied external voltage and maintains the desired temperature with an accuracy of 4 × 10 ^-3 ° C (on the graduation of the platinum resistance thermometer daisy type, which is also located on the surface of the single crystal of Tall piezoelectric material (1)); The third task of providing the possibility of simultaneously conducting acoustic at a surfactant and no less sensitive optical measurements of nanofilm samples in one experiment is solved by the fact that instead of carrying out synchronous measurements on a surfactant and optical measurements in the infrared region of the spectrum in a single absorption-reflective mode, synchronous measurements on surfactants and optical in the waveguide mode of transmission of light of the visible range (MNVPO mode or multiple reflective absorption modes m); The 4th task of simplifying and significantly reducing the cost of the sensor design is solved by the fact that, firstly, in the known device, instead of a unique heating element, which is a piezoelectric single crystal - quartz with a channel made inside it, a heater is used from industrially produced and very cheap CHIP- resistors, secondly, in contrast to the known device, in the inventive device there is no reflective gold nanofilm located between the IDT (FIG. 1).

The capabilities of the proposed invention (device) of a bifunctional acousto-optical sensor in studies of intermolecular interactions involving monolayer, multilayer, gene-antigen nanofilms, protein molecule binding, etc., are demonstrated by studies of the ammonia vapor sorption process that has been studied previously. from the gas phase by a nanofilm of a functional polymer - polydimethylsiloxane (PDMS) with ion-bound fragments of organic dye cations - brilliant green (BZ) [ oborover EI, Zubkov IL Highly efficient flat-waveguide optical chemical sensor design. // Sensors and systems. 2003, issue 4. C.2-7]. A PDMS nanofilm with a thickness of (0.107 ± 0.014) μm (107 nm), which corresponds to approximately the thickness of 50 monomolecular layers, is deposited from a suitable solution using a microsyringe into the space between the IDT onto the surface of a piezoelectric - AT cut crystal (design - “delay line” on surfactant ”with a resonant frequency of 170 MHz). Residual solvent removed under high vacuum. Ammonia is fed to the film surface as part of the air stream in a mode of increasing concentration in the stream. Acoustic measurements — measurements of the SAW frequency and optical measurements of the transmittance of 645 nm (the light source is a semiconductor laser diode) using measurements of the voltage drop across the photodetector were carried out at several temperatures of the nanofilm sample: 24, 34, 44, and 54 ° C. From kinetic acoustic and optical data (figure 3) are built isotherms of sorption of ammonia nanofilm functional PDMS (figure 4). Further, according to well-known formulas from thermodynamics, all thermodynamic parameters of sorption are calculated: Gibbs energy, enthalpy, and entropy (table).

Table. Thermodynamic parameters of the process of ammonia sorption by PDMS film ΔG ⁰ ₂₉₇ , kJ / mol ΔН ⁰ , kJ / mol ΔS ⁰ ₂₉₇ , J / mol · K Acoustic measurements - (18.08 ± 0.34) - (25.8 ± 7.1) - (26 ± 25) Optical measurements - (14.4 ± 0.6) - (84.0 ± 11.0) - (234 ± 40)

Based on the fact that optical measurements in the visible spectrum only control the chemisorption process due to the intermolecular interaction of ammonia molecules with BZ cations that make up the polymer film, and acoustic measurements control the entire sorption of ammonia molecules, including physical sorption and chemisorption, a comparison of thermodynamic parameters calculated from optical and acoustic data. Subtracting the values of thermodynamic parameters obtained from acoustic data from the values of thermodynamic parameters obtained from optical parameters, we can obtain contributions to the thermodynamic parameters of sorption due to chemisorption and structural relaxation of polymer chains resulting from chemisorption. The given example demonstrates that the application of the claimed design of a bifunctional acousto-optical sensor (device) made it possible to bring the sensitivity of optical measurements closer to the sensitivity of acoustic measurements, to synchronously perform both measurements in the range of positive temperatures and, as a result, obtain unique data not available to other devices and the like devices - bifunctional acousto-optical chemical sensors.

Brief Description of the Drawings

Figure 1. The design of a bifunctional acousto-optical sensor: (1) - a single crystal of a piezoelectric, (2) - a sample of the studied nanofilm, (3) - interdigital transducers made of aluminum or gold, (4) - RF amplifier, (5) - visible light source range, (6) - photodetector, (7) - chip resistors forming a heater, (8) - temperature sensor.

Figure 2. The scheme of the passage of light through a waveguide - a single crystal of a piezoelectric (1) in the MNVPO mode - (a), in multiple reflection-absorption mode (b); (2) - sample of the investigated nanofilms.

Figure 3. Kinetic dependences of changes in the SAW frequency (Hz) and the voltage drop across the photodetector (B) in the presence of various concentrations of ammonia in the air flow (sample temperature of the studied nanofilm 24 ° C).

Figure 4. Sorption isotherms constructed from acoustic and optical data.

The design of the bifunctional acousto-optical sensor consists of a piezoelectric single crystal with transparency in the visible spectrum (1), on the surface of which interdigital transducers (IDT) are formed from aluminum or gold (3). A sample of the studied nanofilm (2) is placed (deposited) in the space between the IDT. In addition, the sensor design includes a high-frequency amplifier (RF amplifier) (4), a visible light source (5) and a photodetector (6). In addition, the sensor design includes chip resistors that form the sensor heater and are located along the perimeter (7), the temperature sensor is a platinum resistance type thermometer (8). The piezoelectric single crystal together with the IDT forms a SAW element called the SAW delay line, in which one IDT is a SAW generating transducer, and the second IDT is a receiving SAW transducer. The SAW element is included in the feedback circuit of the RF amplifier, forming a SAW frequency generator, which can be in the range from 30 MHz to 1 GHz (1st harmonic). Almost any visible light source can be used as a visible light source: an incandescent light bulb, a light emitting diode, a laser diode, etc. Any photoelectric transducers that are sensitive to visible light can be used as a photodetector: vacuum type - photocell, photoelectronic multiplier, semiconductor type - photodiode, phototriode, etc. Almost any known standard size of chip resistors with two conditions can be used in the sensor heater viyami: 1. heating power, which is used as an electrical circuit, consisting of multiple-chip resistors, should ensure the achievement and maintenance of the sensor temperature from 20 to 70 ° C under conditions of measurements made in the laboratory; 2. The chip resistors that form the sensor heater must have such geometric dimensions that they can be freely located on the same frontal face of the piezoelectric single crystal on which IDTs are located and not introduce electrical interference into IDT operation. As the temperature sensor, any type of platinum resistance thermometer (PTS) of the petal type can be used that meets two requirements: 1. The calibration of the PTS should provide a temperature resolution of at least 4 · 10 ^-3 ° C; 2. A PTS, which is located on the same frontal face of a piezoelectric single crystal on which IDTs are located, must have such geometric dimensions that it does not introduce electrical interference into the IDT operation.

A bifunctional acousto-optical sensor designed for physicochemical and biomedical research of nanofilms works as follows. First, a measurement sample is made, for this, the investigated nanofilm is applied to the space between the IDT of the SAW element. Then, the elements of the measuring system are electrically switched on: the frequency meter, which is a SAW frequency meter, is turned on, and power is supplied to the RF amplifier, after which the SAW generator starts working and the value of the SAW frequency appears on the indicator device of the frequency meter. After that, the power of the light source and photodetector is turned on. The adjustment of the position of the light source is performed — the necessary angle of incidence of the light beam on the end face of the piezoelectric single crystal is displayed, which allows one of the modes of light transmission through the sample to be realized: MNVPO or repeatedly reflective-absorbing. Then, using the principle of “maximum response”, the position of the input window of the photodetector is adjusted. Then, a supply voltage corresponding to the selected sensor temperature is supplied to the heater. Monitoring the temperature of the sensor is carried out using a temperature sensor, in this case, a PTS pre-calibrated in a high-precision thermostat in the coordinates: electrical resistance (R, Ohm) - temperature in degrees Celsius or Kelvin. Further, the temperature of the sensor is adjusted to the set temperature by fine-tuning the supply voltage supplied to the CHIP heater. Subsequently, during any physicochemical or biomedical process in which the studied nanofilm is involved, synchronous continuous recordings of the readings of the frequency meter (Hz) and the photodetector are made.

Claims (1)

A bifunctional acousto-optic sensor based on a surface acoustic wave (SAW) delay line with a resonant frequency in the range from 30 MHz to 1 GHz, containing a piezoelectric single crystal transparent to visible light from 0.4 to 1.0 μm, on the surface of which two interdigital transducers (IDTs) of aluminum or gold are formed by photolithography, in the space between which the studied nanofilm sample is placed, a visible light source and a photodetector that differs That several chip-resistors, conductors connected in series and forming a total resistance heater with a few kilohms, allowing to support any of the sample temperature in the range of from 20 to 70 ° C with an accuracy of 4 × 10 ^-3 ° C, the thermal sensor are fixed on the surface of the single crystal, which is a platinum resistance thermometer of the petal type, while the light source and photodetector are installed in such a way as to introduce a light beam into the end face of the single crystal and measure the intensity of the light emerging from the counterfield the front end of the single crystal, which, propagating through the single crystal as a plane waveguide in the space between the IDTs, probes the nanofilm sample along its entire length, either in the MNIPO mode or multiple reflection-absorption mode.

Images