JPH0593723A - Lachrymal substance measuring instrument - Google Patents

Abstract

PURPOSE:To continuously measure substances, such as lactic acid, etc., contained in a tear liquid. CONSTITUTION:A reaction electrode 1, an auxiliary electrode 2, an auxiliary measuring instrument 4, a transmitter for remote measurement, and a battery 6 are connected to each other through lead wires 7. They are contained and supported in a supporting body 3 having the shape of a contact lens in a connected state. The supporting body 3 is formed to a porous body of a soft synthetic resin so that the body 3 can adapt itself to an eyeball 12 and a tear liquid can pass through the body 3. An enzyme fixing film 8 composed of, for example, lactic acid oxidase for oxidizing lactic acid is formed on the outer periphery of the electrode 1. For example, the lactic acid contained in the tear liquid is oxidized by means of the film 8 and, accordingly, an electrochemical reaction takes place between the electrodes 1 and 2. Therefore, an oxidation- reduction potential is generated as a physical quantity and an electric current starts to flow between the electrodes 1 and 2. The concentration of the lactic acid can be continuously monitored from the value of the electric current.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus for measuring tear material.

[0002]

2. Description of the Related Art Heretofore, it has been attempted to measure a tear fluid (conjunctival sac fluid) substance in grasping a physiological condition of a human and diagnosing an eye disease. A conventional general method for analyzing a tear fluid is to collect the tear fluid with a glass capillary or the like and analyze the tear fluid separately.

[0003]

However, in the above-mentioned conventional method, since the analysis is performed after collecting tear fluid, it is not simple and it is impossible to continuously measure the target substance.

On the other hand, for the diagnosis of retinal disease, electroretinograms have been measured using contact lens type electrodes that can be used in the conjunctival sac region, and this measurement system measures the potential of the retina. Yes, it does not directly measure tear material.

[0005]

SUMMARY OF THE INVENTION The present invention has been devised in view of such conventional points, and its object is to be able to be directly attached to the eyeball and continuously to the tear material. Is intended to provide a device that can measure
Such a problem is that it has a form that can be worn on the eyeball and that is selectively sensitive to a tear substance and that includes a sensitive unit that generates a chemical amount or a physical amount by the response to the tear substance. This is achieved by the technical means of measuring the concentration of the tear substance based on the resulting chemical or physical amount.

[0006]

Embodiments of the present invention will be described below with reference to the drawings. First, the configuration of the measuring device will be described with reference to FIGS. 1 (a), 1 (b) and 1 (c). 1A is a plan view, FIG. 1B is a cross-sectional view taken along the line AA of FIG. 1A, and FIG. 1C is an enlarged view of part B of FIG. 1B. ..

Reference numeral 1 is a reaction electrode, and the reaction electrode 1 is constituted by a square thin plate made of, for example, 0.2 mm × 0.2 mm made of gold. Reference numeral 2 is an auxiliary electrode, and the auxiliary electrode 2 is composed of a square thin plate made of, for example, 2 mm × 2 mm made of silver.

Reference numeral 3 is a support, and the support 3 has a substantially disk-shaped planar shape made of a porous synthetic resin having a high flexibility, which is easily adapted to an eyeball of a human body. The support 3 has a hollow shape with a convex portion 3a on the front surface and a concave portion on the back surface, like a general contact lens.

Reference numeral 4 is a measurement assisting device, 5 is a remote measurement transmitter, and 6 is a battery. Reference numeral 7 is a lead wire, which connects the reaction electrode 1, the auxiliary electrode 2, the measurement auxiliary device 4, the remote measurement transmitter 5, and the battery 6 to each other.

The measurement auxiliary device 4 is called a potentiostat, and the measurement auxiliary device 4 is connected via a lead wire 7 between the reaction electrode 1 and the auxiliary electrode 2, for example, 70.
A constant voltage of 0 mV is applied, and the resulting current is measured by the measurement auxiliary device 4.

The measurement assisting device 4, the remote measurement transmitter 5, and the battery 6 are fixed and sealed in a comprehensive state inside the support body 3 when the support body 3 is molded with the lead wires 7 connected thereto.

Reference numeral 8 is an enzyme-immobilized membrane made of lactate oxidase for oxidizing lactic acid. The enzyme-immobilized membrane 8
Is, for example, 4.5 mg derived from Pediococus sp (enzyme activity 33.0 unit / mg) manufactured by Toyo Brewing Co., Ltd. is mixed with 50.3 mg of photocurable resin PVA-SbQ manufactured by Toyo Gosei Co., Ltd., and 30 μL of distilled water, and the mixture is mixed as described above. The electrode 1 is coated so as to wrap it, dried in the dark for 1 hour, and then irradiated with a fluorescent lamp for 15 minutes. It should be noted that the enzyme-immobilized membrane 8 is hydrophilic, and liquid such as tear fluid and biological substances therein reach the interface between the enzyme-immobilized membrane 8 and the electrode 1 through the enzyme-immobilized membrane 8. You can In addition, since the support 3 is porous, liquids such as tear fluid and biological substances therein are passed through the porous portion of the support 3 to the electrodes 1, 2 and the enzyme-immobilized membrane 8 and the support 3. Can reach the interface with.

Next, a method of attaching the tear fluid measuring device 9 having the above-described structure will be described with reference to FIGS. 2 (a), 2 (b) and 2 (c). FIG. 2A is a diagram showing the eye part of the subject.
2B is a side view thereof, and FIG. 2C is a sectional view of FIG. 2A.

The mounting method is similar to that of a general contact lens, in which the concave portion of the support 3 of the measuring device 9 is directed upward and the convex portion 3a is placed on the fingertip side, and distilled water is placed in the concave portion.
Saline is added dropwise. In this state, the eyeball 12 under the eyelids
The measuring device 9 is attached to the. At that time, the measuring device 9 and the eyeball 1
2 is in close contact with each other due to surface tension through a thin film of the mixed liquid of the above-mentioned dropping liquid and tear liquid 13. The surface tension allows the measuring device 9 to be continuously mounted. Further, since the measuring device 9 is in a thin film state similar to a general contact lens, there is no obstacle in opening and closing the eyelids. In the figure, 10 is an upper eyelid, 11 is a lower eyelid, and 12 is an eyeball.

Explaining the whole apparatus shown in FIG. 3, 14 is a subject, 15 is a telemetry receiver, 16 is a recorder, and 17 is a recorder.
Is an analyzer, and 18 is a lead wire for connecting each device.

Next, the operation will be described. In the measuring device 9 attached to the eyeball 12, tear fluid containing a biological component existing outside the measuring device 9 due to opening and closing of the eyelid is passed through the porous portion of the porous support body 3 to form the electrodes 1, 2 And reaches the enzyme-immobilized membrane 8. And the enzyme-immobilized membrane 8
Especially, lactic acid in the tear material which has reached the temperature is oxidized by the lactate oxidase of the enzyme-immobilized film 8 fixed on the entire circumference of the reaction electrode 1 to generate the following reaction.

[0017]

## STR1 ## in _{C 3 H 6 O 2 + O} 2 → C 3 H 4 O 3 + H 2 O 2 H 2 generated in the reaction O ₂ electrodes 1, 2 in phosphoric acid electrolyte in the tear fluid In between, it causes the following electrochemical reactions.

(The margin below)

[0019]

## STR2 ## ^{_{H 2 O 2 → 2H + +}} O 2 + 2e - 2H + + PO 4 3- → H 2 PO 4 - H 2 PO 4 - → 2H + + PO 4 3- O 2 + 2H + + 2e - → H 2 ^{_{O 2 Ag 2 O + 2H +}} + 2e - → 2Ag + H 2 O according redox potential as a physical quantity between the electrodes 1, 2 by an electrochemical reaction is generated, said current is electrically in measuring auxiliary apparatus 4 via the lead wires 7 Get burned. The current measured by the measurement auxiliary device 4 is received by the telemetry receiver 15 via the telemetry transmitter 5, recorded by the recorder 16 and analyzed by the analyzer 17.

As a result, the lactic acid concentration can be continuously measured non-invasively without damaging the human body with the substance in the tear fluid. The present invention is not limited to the above embodiment, but various modifications can be made as follows.

(1) It is also possible to comprehensively support the portions other than the electrodes 1 and 2 with the support 3 and mount the electrodes 1 and 2 in a thin film on the surface of the support 3. (2) In order to eliminate the influence of an interfering substance such as ascorbic acid existing in the tear fluid, the reaction electrode 1
In addition, another reaction electrode that does not immobilize lactate oxidase is installed, and the current related to electroactive substances other than hydrogen peroxide is measured at the reaction electrode, and the current related to lactic acid and the current related to other active substances are measured. It is also possible to detect the difference from the above and to monitor only the enzyme reaction part due to lactic acid.

(3) The support 3 can also be used as a contact lens by forming a lens portion made of the same or different material in the central portion 3a. (4) leaving the electrodes 1 and 2 and the enzyme-immobilized overmembrane 8 on the support 3,
It is also possible to place the other part in the external environment and lead it to a device in the external environment with a lead wire by means of the electrodes 1 and 2 and measure it by wire.

(5) Since the reaction rate of the enzymatic reaction changes with temperature, temperature compensation may be performed to keep the reaction constant. (6) The electrolyte is not limited to phosphate ions and may be another electrolyte in tear fluid.

(7) The tear substance is not limited to lactic acid, but glucose, pyruvic acid, phenol, lipid, uric acid, glutamic acid, urea, arginine, lysine, phenylalanine, creatine, amino acid, sodium, potassium, ammonium, chlorine, Ions such as calcium, magnesium, copper, bromine, fluorine, zinc, etc., or hormones such as adrenaline, noradrenaline, dopamine, GABA, thyroid hormone, adrenocorticotropic hormone, etc., and other alkaline phosphatase, myeloperoxidase, superoxide dimestase Enzymes such as lysozyme are known.

The present invention can also be applied to measuring the concentration of such a tear substance. And as an enzyme sensor in the sensitive part, for example, glucose oxidase for glucose, pyruvate oxidase for pyruvate,
Enzymes that oxidize each tear substance, such as tyrosinase for phenol, cholesterol oxidase for lipid, and uricase for uric acid, may be used.

(8) The application of the present invention can be applied to exercise physiology, medical field, management of elderly people in daily life, etc., and also depends on visual perception such as CRT work using a monitor screen and driving a car. It can also be applied to evaluation of eye strain associated with such work and grasp of physical condition.

[0027]

As described above in detail, the present invention has an excellent effect that the tear material in the eyeball portion can be directly measured in real time and continuously.

[Brief description of drawings]

FIG. 1 is a diagram showing a measuring device.

FIG. 2 is a diagram showing a state in which the measuring device is attached to an eyeball part of a human body.

FIG. 3 is a diagram showing a measurement system using a measurement device.

[Explanation of symbols]

 1 Reaction Electrode 2 Auxiliary Electrode 3 Support 4 Measurement Auxiliary Device 5 Remote Sensing Transmitter 6 Battery 7 Lead Wire 8 Enzyme Immobilized Membrane 9 Measuring Device 12 Eyeball 15 Remote Sensing Receiver 16 Recorder 17 Analyzer

Claims (1)

[Claims] 1. A sensing part which is adapted to be worn on the eyeball and which selectively senses a tear substance and which produces a chemical amount or a physical amount by the response to the tear substance. An apparatus for measuring a tear substance characterized in that the concentration of the tear substance is measured on the basis of the above-mentioned chemical or physical quantity.