JPS6042908B2 - Stabilization method for biological FET sensor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for stabilizing a field effect transistor (FET) sensor having a selectively sensitive membrane in the gate insulator.

In recent years, in the fields of physiology and medicine, substances in body fluids represented by blood, such as ions such as H, Na, Ni, Cl-, O
2. Concentrations of gases such as CO2, other sugars such as glycose and lactose, hormones, enzymes, antibodies, etc. are now frequently measured.

However, the conventional measurement method of directly collecting and analyzing body fluids requires time and effort for analysis, making it difficult to cope with the recent increase in the amount of measurement. Therefore, the need for continuous monitoring of the above measurements has recently begun to be recognized. Various for these purposes. Measurement methods are being considered, including the one reported by Matsuo et al.
T0Matsu0and, DWise11EEETr
ans｜0nBME, 21, N06pp485-487
, 1974) H sensor using Si3N4, SiO2, etc. as a sensitive film, Na sensor using an alumina silicate film
゛Ion sensors such as sensors, enzyme electrodes using enzyme membranes, immune sensors using antibody reactions, gas sensors using ion exchange membranes, etc. can be easily miniaturized, have simple measurement circuits, and are easy to use. It is a very promising sensor for biological monitoring because it is inexpensive and it is possible to measure various substances by changing the selective permeation membrane in the gate part.

Although these FETs can be fully used as sensors as they are, they have the drawback of showing extremely unstable measured values when measured in living organisms. For example, although stable measurements can be made in a buffer solution, drift occurs in blood, and even the same concentration often shows different values with no reproducibility due to changes in the individual being measured or the measurement site, making it unsuitable as a biological monitor. It was hot. As a result of various studies, the present inventors deduced that the unstable measured values in the living body are mainly caused by the adsorption of proteins, etc. in body fluids to the sensor section, and furthermore, measures were taken to prevent the adsorption of proteins, etc. As a result of extensive research into its use as a biosensor, stable measurements were achieved by coating the selective sensitive membrane in the FET gate area with a porous polymer that has pores that allow the substance to be measured to pass through, but do not allow macromolecules such as proteins to pass through. It was found that the value of These effects are particularly remarkable in the case of ion sensors. The porous polymer used for coating in the present invention is
Although the polymer material itself does not transmit the substance to be measured,
It is a membrane that allows low molecular weight substances to permeate through the pores in the membrane, specifically membranes such as those used in dialysis membranes, reverse osmosis membranes, and ultrafiltration membranes, and the material is acetyl cellulose. , nitrocellulose, PVCl nylon, polycarbonate, Teflon, etc.

These membranes must be permeable to ions to be measured, but desirably not permeable to proteins in blood, and the maximum diameter of the pores must be 40A or less. Further, the larger the proportion of pores, the faster the response speed, which is advantageous, and it is preferable that the material has a water content of 10% or more when immersed in water. The FET gate portion can be coated with these films by a method similar to that used for forming ordinary ultrafiltration films, such as a known phase separation method or extraction method.

The form in which the gate portion is coated with the film is simply F as shown in Figure 1a.
In addition to those in which a polymer film is formed around the gate part 2 of the ETl, there are also ones in which the FETl is placed in the tube 4 and a porous polymer is filled between the gate part 2 and the tube, as shown in b. In this case, the film thickness is determined by the distance d between the gate part and the part of the film that is in contact with body fluids.
Defined by If the thickness of these films is too thin, not only will there be problems with strength, but also the effects of substances adsorbed on the polymer surface will appear, and if they are too thick, not only will the response time be slow, but this is the most important feature of FET sensors. Since it goes against the purpose of miniaturization, the thickness of the polymer film should be 0.1 μ to 1
Wf! Ft is preferred. The FET sensor stabilized as described above is similar to the conventional FET sensor without polymer coating.
It can be measured using the same circuit and method as the sensor, and it is not only possible to obtain stable measured values in vivo, but also has excellent anti-blood test properties.

Next, the present invention will be specifically explained using examples.

Note that the FET for PH and Na+ measurement used in the examples
is based on the structure of the FET reported by Matsuo et al., and the measurement was carried out in the same manner as in the same literature by keeping the drain-source voltage VDS and drain current 1D constant and measuring the gate-source voltage. Ta. Example 1 A porous acetylcellulose membrane was formed at the tip gate portion of an FET pH sensor having silicon nitride as a sensitive membrane by the following method.

That is, 17 parts of acetyl cellulose, 69 parts of acetone.
2 parts, MgClO4l. 45 parts of acetylcellulose and 12.35 parts of water were thoroughly mixed and dissolved, and the acetyl cellulose solution was applied to the FET gate area, and after evaporating a portion of the solvent at 10°C for 5 minutes, the solution was mixed with water at 0°C. Soak in and gel. moreover,
After washing this with water, it is heat-treated in 70°C hot water to obtain a porous membrane. The tip of the FET thus obtained was immersed in water for a day and night, and then VGS was measured in blood and in a buffer solution having the same pH as blood. The results are shown in the following table. (Id=30μA
NVDS=2V) F not coated with acetylcellulose
ET gradually drifts to lower VGs in the blood and reaches equilibrium at a value that deviates from the buffer solution by 50rT1v, whereas
The FET coated with acetyl cellulose stably showed correct values. Example 2 A porous EVA (ethylene vinyl alcohol copolymer) film was formed on the tip gate portion of a -FETNa sensor having aluminosilicate as a sensitive film by the following method.

That is, a nodule of EVA (ethylene content: 33 mol %) is dissolved in 80 parts of dimethyl sulfoxide, applied to the tip of the FET, and then immersed in water at 5° C. to solidify the EVA. After immersing the FET obtained in this way in distilled water at room temperature overnight, measurements were taken in blood and in a buffer solution with the same Na concentration and pH as blood. As a result, the FET without EVA coating drifted in blood. Although this occurred and a value lower than the actual Na+ value was obtained, accurate values could be stably measured using the EVA-coated FET.

[Brief explanation of the drawing]

The drawings show an example in which a porous polymer film is coated on the FET gate insulating part, and Fig. 1a shows an example in which a polymer film is formed on the gate part, and Fig. 1b shows an FET gate insulating part coated with a porous polymer film.
is placed in a tube, and a porous polymer is filled between the tube and the gate.

Claims (1)

[Scope of Claims] 1. A method for stabilizing an FET sensor, which comprises coating a porous polymer film on a field effect transistor having a selectively sensitive film in an insulated gate portion. 2. The method for stabilizing an FET sensor according to claim 1, wherein the porous polymer membrane has a thickness of 0.1 μ to 1 mm. 3. The method for stabilizing an FET sensor according to claim 1, wherein the porous polymer membrane has a pore diameter of 40 Å or less.