JPS59500896A - Oxygen partial pressure measuring device using optical fiber - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Original fiber PO2 probe This application was previously filed in U.S. Patent Application No. 363.425 on March 30, 1982. The application is a partial continuation application with the title of the invention "Optical fiber oxygen partial pressure (PO2) probe". Regarding FJ-3 of the above-mentioned application, please refer to the references.

Field of the invention The present invention relates to the measurement of oxygen partial pressure, and especially to measuring the total oxygen partial pressure in blood + tissue. Regarding the original fiber probe device U to be input.

Background of the invention Physiological measurements are difficult to determine for a number of reasons, as described below.

0 Transfer function (Figure 1) is a fundamental determinant of oxygen transport and distribution.

Q. Adsorption of 02 to heme is the most widely used method for oxygen storage and transport in the animal kingdom. This is the mechanism that is used.

0 The corresponding protein change (globin) that fits heme controls its adsorption properties and Determine the shape of the dynamic function and adapt the hem to the requirements of the special mallet.

The O-globin chain also plays a role in biochemical signals, especially the noble pi(,2,3-diphosphoglycerate). part of the control loop for adjusting the curve to C02 and C02.

○ Approximately 200 genetic mutations of hemoglobin are known in humans, and most of them are , harmless, but some of them are pathological due to altered transport function (such as sickle cell disease) There is.

0 Therefore, the direct alignment of the oxygen partial pressure PO2 is the enzyme of the individual in the physiological tattoo. This is necessary to observe transportation behavior.

In addition, adequate tissue oxygenation is important for rapid sampling and PO2 levels. Continuous monitoring of the most critical conditions in gradual surgical or intensive nursing situations that require continuous monitoring of all It is one of the easiest things to use.

Several techniques and systems are known, but none of them are optimal. stomach. for example, Clark electrodes (membrane-diffusion, current) do not contribute to miniaturization.

Anything that relies on diffusion has the problem of polarization and deviation.

Strictly differential (potential reduction) electrodes are particularly difficult.

U.S. Pat. No. 4.20], 222 (Haase) describes the Pressure ′fj: In order to sub-determine the discloses an optical catheter.

This catheter has a semi-transparent plate that allows the gaseous part of the blood to pass through and prevents the liquid part of the blood from entering. Defeat from wood. The intensity of the reflected visible light entering the original fiber is compared to the intensity of the incident light. , which corresponds precisely to the partial pressure of oxygen gas in the blood stream.

U.S. Patent No. 3.814.081 (Mori) discloses that blood fL Discloses an optical catheter for measuring the percentage of HA content that saturates at are doing. The light emitting fiber optic stem and the light receiving system are all placed adjacent to each other.

The tip of the catheter is inserted into a blood-carrying organ in the animal's body. Awakening saturation, blood Anti-J from style? 11/, 'C performance by optical absorption spectroscopy analysis of light waves received in the original fiber. 1] Determine.

U.S. Patent 3.8 Q 7.390 (Ostrowski et al.) Insert the catheter tip into the tubing system and remove the oxygen from the plate of active human blood flow. A fiber optic catheter for monitoring saturation conditions is disclosed.

U.S. Pat. and a general reference illustrating an optical pH measuring device for determining the pH of blood. Indicates related matters.

U.S. Pat. Teach the equipment used to measure and monitor the concentration, partial pressure, and pH of blood over various time periods. Indicates generally relevant information.

There is a lot of literature on PO2 electrodes, but there are no useful electrodes.

Measurement of oxygen by luminescence quenching is also taught.

Although the idea was born in the 1930s, it was hardly ever put into practical use. However, oxygen quenching of fluorescent light is widely known to be harmful. US Patent 3.612.866 (Stevens), aromatic molecules, their derivatives, and aliphatic ketones. Oxygen-containing liquid or gas based on the molecular luminescence quenching effect of physical oxygen. Discloses an arrangement for measuring coagulation.

Other applications of lumitsusensense quenching for oxygen measurements include (1) “Silica gel adsorbed dyes”. Initial observation of the effect of JH, Kautsky and A, Hirschi x (H irsch) In the early 1930s, for example, H. Kalacki and A. Machinery and General Chemistry” 222.126-34.1935゜ (2) "Measurement of 02 by HO illumination", M, Pollack, P., Pringsheim, D., Tarwood (T. erwood), Chemical Physics Journal (, T, CC11e, Phys,) , 12.295-9.1944° Overview of photosensitivity j1. B. Berlman “Fluorescence Spectrum of Aromatic Molecules” "No Ndopsk of Kutor", Akademik Publishing (Acade + 1llc Pre ss), 1965゜(4)　10 using 7 Cliff Lavin on acrylic sheet tO "02 measured by r", Gy, Open (Zs with Qrban, Suentee May (Szentirmay), J, Pan: T (Patko), “Pro c, of the Intl, Conf, on Lum1nescence”, 1966, V, 11611-3.1968゜(5) [rod s) ``Diffusion efficiency of 02 in AcryA・class measured by 9-dimensional observation'', G, Sha (Sliawn, trance.

779 Day Society (Trans, Faraday Soc,) 63 ．． 2181-9, 1967゜ (6) “02 transmittance JP of acrylic film measured by extinction ratio vs. PO2, F. Jones, Polymer Lett ers) 6.487-91.1968° (7) r plus snack film and 7A-off7ze:y (f Based on 1uoranthene) (PO2O2 measurement mouthpiece, Bergmann (Be rgman), 4-char (Nature) 218.396.1968° (8) “Butyric acid used as a probe for intracellular 02 measurement”, 50 people , Knopp, 1. A. Longmuir Chemistry and Life Physics Biochimica et Biophysica Ac ta) 279.393-7.1972° (9) 1 In the form surrounded by various membranes Measurement of physiological PO2 using a DMF solution of pyrenebutyric acid JD, W, Lapper ( Lubber), N, Obitsu (Qpitz), z, 4-chuaf (Natur f), 30c, 532 3.1975° Summary of the invention In view of the above, an object of the present invention is to solve the above-mentioned drawbacks of the known techniques. .

Another object of the invention is to provide improved in-vivo PO2 measurement.

Another object of the present invention is to provide an improved PO2 measuring device, especially a luminescence quenching device. To provide an apparatus based on oxygen measurement using an optical fiber probe and having an optical fiber probe. It is.

Furthermore, another object of the invention is to use luminescence quenching as the working principle and to A relatively simple optical system that combines a magnification tube and is operated by the optical magnification tube. and PO2 based on the luminescence quenching detected by the optical system. An optical fiber that combines electronic arithmetic circuits that perform direct analog calculations. -Used a probe. An object of the present invention is to provide a PO2 measuring device.

Typical optical fiber for oxygen partial pressure measurement based on the principle of fluorescence quenching according to the invention The probe has a plastic tube-shaped end with a porous cross section and a diameter of 06 mm and a length of approximately 5 m. Two 150 micrometer strands of plastic optical fiber with Consists of - The tube contains the dye on an absorbent particulate support. child The basic structure of is described in U.S. Patent 4.20 of Peterson et al. This is similar to the physiological pH probe disclosed in US Pat. No. 0.110.

In the development of the probe of the present invention, the above-mentioned extinction principle has been developed. Three main problems needed to be solved. That is, 1. The dye has appropriate oxygen quenching sensitivity (long life in active state) and fluorescence excitation by visible light. It is necessary to find a material that has both properties such as high brightness and resistance to fading. do not have. Plastic optical fibers that transmit light with wavelengths shorter than 45Qnm are not used. I can't do it. UV-transparent inorganic fibers are brittle and therefore unsuitable for the present invention. .

28 A suitable hydrophobic, high oxygen permeable envelope was required.

3. The adsorbent support needed to maintain moisture resistance to activate the dye. Conventional Silica dye supports are not suitable for use in aqueous media.

The probe device of the present invention is small and low profile, suitable for injection into tissue or blood vessels via a skin needle. It provides a price guide.

The optical fiber probe has the following advantages.

a, Q, 5! II! Extremely small sizes such as θ or less are possible.

b.It is flexible and can be threaded through small blood vessels and into various tissues. You can go inside.

C1 is cheap, disposable, and easy to manufacture.

d.Does not cause electrical interference.

e. It is more suitable for static measurements than mechanical methods.

The choice of luminescence quenching as an instrument for oxygen measurement is based on the following factors:

1. A reversible indicator is required for the PO2 probe. Reversible colorimetric determination for oxygen (absorbance ) The indicator is inappropriate. Transition metal complex oxygen adsorbents do not have the necessary stability. stomach.

2. When activated by light absorption, aromatic molecules form charge-transfer complexes with oxygen. . This results in an inert fluorescent state mechanism characteristic of oxygen. Due to collision movement It is not necessary for the activation energy of the molecule to be high enough to form active oxygen, i.e. The quenching phenomenon can be dreamed of by activating the visual light of the Lumi 4 senses.

Fluorescence (and phosphorescence) quenching is a non-luminescent reaction that counteracts the luminescence decay of active molecules. This is a result of the sense decay mode, and the average lifetime of the active state decreases and the emission intensity also decreases. Ru. (See Figure 2) According to a constant illumination, the decay rate of the excited state varies between various decay modes. The collision decay rate is approximately proportional to the average life of the active state and the collision rate. The collision rate is proportional to the pressure of the quenching gas (comparable to the fluorescence lifetime). These antagonistic collapses The rupture rate is determined by the Stern-Former equation where the partial pressure of oxygen P is the intensity I of O2.

(0, Stern & M, Vollmer, Fujikaritssier, Zeitschrift, 20.183-8, H919), where 0 is the intensity of the state without quenching. degree, Pl is a constant and the pressure of the oil light state. The constant means the fluorescence lifetime and the corresponding quenching Since it has a proportionality, the above equation can be expressed using the observed luminescence lifetime, TO and T. be able to.

Good sensitivity of quenching requires long average lifetime excited states. Extremely long lifespan ( Phosphorescence with a period of several seconds) is sensitive to quenching, but the intensity is weak. Fluorescence is sensitive to quenching. Although the intensity is low, it has high brightness (high quantum yield). p+ is the best compromise between brightness and sensitivity is in the class of pressure to be measured in order to obtain . (See Figure 3) Brief explanation of the drawing Other objects and advantages of the invention will be found in the following description and claims, as well as in the appended claims. This will become clearer from the drawings. By the way, Figure 1 shows the classical concentration of oxygen in the human body's blood. It is a graph showing the relationship between pressure and pressure.

FIG. 2 is a schematic illustration of the competitive mode of inactivation of optically excited molecules.

FIG. 3 is a schematic diagram showing the relationship between P' and PO2.

FIG. 4 is an illustration of an embodiment of a POz probe according to the invention.

Figure 5 shows typical observation data and theoretical values of the Stern-Former according to the present invention. This is a comparison graph.

Figures 6 and 7 show a simple analysis using an optical system according to the invention and an inspection probe. FIG. 3 is a diagram schematically illustrating the electronic calculation system of the log device.

Detailed transparency of the preferred embodiment In the accompanying drawings, particularly FIG. 4, the PO2 probe of the present invention is constructed as shown at 8. be done. PO2 probe 8 is made after the already developed pH probe in the process of use. It is something that (See U.S. Pat. No. 4.200.110, Baderin et al.) This PO In the two-probe 8, the dye 15 of the adsorption support 16 is made of polyethylene with a porous cross section. placed inside the tube 10 to quickly equilibrate with the surrounding oxygen and dye inclusions. Protect 16 from contamination.

The tube 10 is closed at one end, creating a narrow, closed tip 9 at the center. A pair of possible The flexible plastic optical fiber 12.14 is, for example, 150 micrometers thick. - Use a stranded plastic optical fiber and attach the fiber to the other end of the tube 10. The ends of the bars are fixed in such a way that they are optically exposed to the dye 15 of the dye-containing body 16. blood Tube 10 is made from a cross-sectional porous polymer tube approximately 5U long and 0.6mm in diameter. Become.

The backlight illumination passes through one of the optical fibers 12 to excite the dye 15°C and fluoresce it. Oko 3-0 The green fluorescent ray with the scattered blue light enters the other light 7 eye bar 14 transmitted to the measuring equipment. (See Figures 6 and 7). Intensity of blue light ■0 is the basis for optical correction The quasi value and [7] are used, and the intensity of green light (■) is the value of oxygen quenching.

The Stern-Holmer relationship is a linear quantification for measuring PO2 due to quenching. Provide standards. (See Figure 5) The relationship between the curves is widely seen (St. Runeformer (there is a large literature on data plotted based on it), We often add an index to oxygen pressure, similar to adding coos.

Although the theoretical interpretation of this exponential relationship is difficult to understand, the curve data is useful when measuring strength. The offset constant can be used to properly match the This can be explained in the case of quenched luminescence. However, for equipment design, the strength ratio It is more practical to use the index m or the bracket index n.

A simple analog device was constructed to calculate the measurements of the probe. (Figure 6 and (See Figure 7) The measurement of PO2 closest to IrrmhgP02 is 0.1%. Requires accuracy greater than the strength measurement error. The limiting factor is the stability of the light source. There is sex.

As mentioned above, there are three characteristics of the above system that need to be selected appropriately, namely: There is a dye 15, a dye support 16, and an envelope 10.

Suitable dyes 15 have the following properties:

a. It does not break when bent at an acute angle, has high flexibility, and is easily optically damaged by burning etc. Visible light that can be transmitted by plastic optical fibers shaped to allow coupling It must be possible to excite the wavelength and generate visible wavelengths.

b. It must be stable to light and have adequate resistance over time.

C1 Must not be toxic.

d. Oxygen quenching sensitivity sufficient to provide the closest measurement to 1 dish oil gPO2. (long average lifetime of excited state).

When selecting dye 15, many UV-excited dyes have high quenching sensitivity (benzene has One of the highest requirements for visible light excitation is the makes it more difficult to find dyes that meet this requirement. Desirable dye base It is a microwaved butyrate. Other desirable dyes are Pylan products. Products) LX 7878゜The dye that can be used is Terra, although it is not optimal. Jill, Brilliant, 7 Rabin (Te r asil Br1lliant F lavine) 80F F1 Nylosan Brilliant Flaviy (Nyl osan　Br1lliant　Flavine)　,7cridine,ix　o　 -(Acridine Yel low), Brilliant Sa#77 7 Lapiy (Brilliant 5ulfaflavine), 2,7-dichloroflavine Luorescein, Acridine Orange, Coumar in 34, Coumarin 6, Fluorescein Natori Auramine, and certain rhodamines.

Others are described in the references cited above.

Regarding the preferred dye support 16, a β-quenching effect has long been observed in silica gel. and high sensitivity can be obtained with this support.

A highly permeable support is necessary to expose individual dye molecules to oxygen bombardment. liquid also Dye baths in solids are not photosensitive due to the low oxygen permeability of these materials.

The problem with inorganic adsorbents is that quenching is sensitive to humidity; Or the fluorescence is destroyed at 100% humidity, which is a physiological measurement condition.

Organic adsorbents such as porous polymers can absorb this humidity at the expense of 7'Ij photosensitivity. Polymers that avoid the problem and can be determined by repeated testing of this description It is preferable to select Porous polymer, Rohm & Haas [Amberly] XAp 4 J (f%ohm & Haas″Amberlite XAD 4”), nonionic hydrophobic polymers are preferred supports 16. Other examples include Qas Chrom Q, Amber Light I　i　　e　　)XAD　2. XAI) 8, Rify (Dow)XFS 4022, Sea R-7 Sue Manguile Chromo Soap (JohnsJvia nville Chromosorb) Nos, 101, 102, 103, 1 04,105,106゜107.108, Waters Polaback (Wate rs Porapak) Nos, N, P, PS, Q, R, S, QS, '11. A water-impermeable container is necessary for the permeable outer packaging method 0 of this example.

Porous polypropylene sheet Celanese "Celguard" (Celgard) j into a tube shape by heat sealing.

The above examples were carried out in an aqueous environment in the same way as in the gas system, and test animals were It worked satisfactorily.

The combined use of optical fiber and luminescence quenching for oxygen II'tll determination is It is considered to be new and excellent. As mentioned above, the important characteristics of the present invention are Use of porous polymeric supports and appropriate selection of dyes and porous coatings or envelopes The use of Using a porous polymer as the dye support 16 has the best effect. It is the key to As mentioned above, desirable coatings 11) i’l: Celgard ( Celgard), but other porous materials can also be used. .

Various configurations are possible, including other ways of making the entire probe, e.g. with two optical fibers. The tip size is The size can be reduced.

In the typical optical system of FIG. 7, the optical output of fiber 14 is collimated. The light is transmitted through a mirror lens 18 to a dichroic filter 19 tilted at 45 degrees. transparent The light component passes through a blue filter 20 9 and reaches a first optical magnification tube 21 . The reflected light component is green It reaches the filter 224-mc and the second optical magnification tube 23. As shown in Figure 6, nine The output currents from the magnification tubes 21 and 23 are supplied to constant current pressure exchange circuits 24 and 25, respectively. The obtained voltage signals are respectively passed through active filters 26 and 27' to This becomes an input to a urine calculation circuit 28 having means for giving an index mf to (Ii/■green). circuit The output of 28 is supplied to the final calculation circuit 29 to calculate the PO2 analog value. Sunawa In other words, the arithmetic circuit 29 subtracts the entire quantity 1 from the input signal, and calculates the coefficient P' as shown in FIG. Put on.

Various modifications may be made without departing from the scope of the invention, and the invention may be modified as shown in the figures. It is considered obvious to a person skilled in the art that the invention is not limited to the content given in the description or the content stated in the specification. .

Engraving (no changes to the content) Ward r one sect g- international search report 1981 I March 10 countries Patent Office” and Palace 1.Displaying 11 items PCT/U882101418 2 Name of the invention Original fiber P02 probe 41 Nsaikai Hill 6, 1-29-' Akashi-cho, Chuo-ku, Tokyo, subject to correction

Claims (1)

[Claims] 1. Oxygen porous coating small enough to pass through the blood vessel, and inside the coating It transports the dye molecules and exposes the individual dye molecules to oxygen bombardment. a highly permeable porous dye support, which is carried by the porous support and emits visible light; A non-toxic dye that is stable against light and aging and has good oxygen quenching sensitivity, and An optical fiber transmits the excitation '''5Yf to the dye and collects all the luminescence from the dye. Measurement of POz4 in blood and tissues of living animals, characterized in that it consists of one means: probe for. 2. The dye is characterized by being veri dibutyrate (color index 59075) The probe according to claim 1. 3. The porous dye support is a porous organic polymer. The probe according to the first or second item of the range. 4. Claim 1, wherein the porous dye support is made of silica gel. The probe described in section. 5. The porous dye support is comprised of a porous granular polymer material. The probe according to claim 1. 6. The porous dye support is Amberlite XAD4 The probe according to claim 1, characterized in that it consists of: 7. The oxygen porous covering consists of a tubular envelope of porous material. The probe according to claim 1. 8. The tubular envelope is made of Celgard. The probe according to claim 1. 9. The oxygen porous coating is heat sealed into a tube with one end closed and 7. It is characterized by being made of a porous polyglobylene sheet material with a tip shape of a photometer. The probe according to claim 1. 10. The optical fiber means has one end extending into the coating and optically exposed to the dye. The material is made of one or more strands of transparent glass fiber. The probe described in item 1 of the scope of the request. 11. The optical fiber means extends into the coating and has an optically exposed end to the dye. It is characterized by being made of two strands of transparent flexible plastic fiber with The probe according to claim 1, wherein the probe is characterized by: 12. The optical fiber means extends into the coating and optically exposes the dye. one strand of transparent plastic fiber with an end T-; optically coupled to the other end of the fiber, separating the two from the source from which the fiber was transmitted. a beam splitting means for forming two separated beams; and a beam splitting means for forming two separated beams; t Electrical signal generating means and a PO2 calculation circuit connected to the output of the photoelectrical signal generating means. The probe according to claim 1, characterized in that it consists of means. 13. A path for the two separated light beams between the light beam splitting means and the photoelectric signal generation means. Claim 12, characterized in that each filter is provided with a different filter means. The probe described in. 14. One of the color filters is a means for transmitting light corresponding to the luminescence wavelength of the dye. On the other hand, one color filter uses the dispersed light of the incident light that exposes the dye and the light that is reflected on the dye. Claim 1, characterized in that only the colored light corresponding to the dispersed light of the incident light is passed The probe described in item 13.