CN1947657A - In-vivo real-time photo-sensitive blood oxygen sensor, and its making method - Google Patents
In-vivo real-time photo-sensitive blood oxygen sensor, and its making method Download PDFInfo
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- CN1947657A CN1947657A CN 200510030572 CN200510030572A CN1947657A CN 1947657 A CN1947657 A CN 1947657A CN 200510030572 CN200510030572 CN 200510030572 CN 200510030572 A CN200510030572 A CN 200510030572A CN 1947657 A CN1947657 A CN 1947657A
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Abstract
An in-body real-time photosensitive blood oxygen sensor is prepared from an ordinary optical fiber and an oxygen sensing film composed of the luminous electrochemical substance with high sensitivity to oxygen and the polymer containing phosphatide group through coating said oxygen sensing film on the terminal of said optical fiber. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to medical apparatus and instruments and material field, be specifically related to a kind of at vivo real-time photo-sensitive blood oxygen sensor and preparation method thereof
Background technology
The rescue of the development of modern medicine, particularly clinical critical patient need comprise that blood oxygen value etc. carries out long Wicresoft and detects in real time to the various parameters of human body.The oxygenation measurement instrument is a principle with the electrode method mainly at present.Present employed method, after all being faced with pick off and blood contacting certain hour, the problem of inefficacy is caused on the surface by protein adherence such as platelet, also exists the difficult problem of similar biological pollution at the pick off of application such as other field such as bioreactor.
The material that can produce electrochemiluminescence has many kinds, and what still report at most is ruthenie complex, as tris (bipyridine) ruthenium and derivant thereof.Existing bibliographical information the method for fixing tripyridyl ruthenium, as the ruthenie derivant of terpyridyl is prepared into L B film and self-assembled film, tris (bipyridine) ruthenium is fixed in the cation exchange membrane.But their stability is all not so good, easily runs off in solution.(J.Phys.Chem.1993 97:2646) at first uses the sol-gel process fixing tripyridyl ruthenium to O.Dvorak and M.K.De Armond; (Anal.Chem.2000 such as A.N.Khramov, 72:32943) tris (bipyridine) ruthenium is fixed in the Nafion-silicon dioxide composite membrane by ion exchange, the modified electrode of gained, its sensitivity and the purer Nafion film of stability have had bigger improvement, but its long-time stability are still not enough.
The existing in the market commercialization instrument that utilizes above method to make occurs, be coated in the electrochemiluminescence high sensitivity oxygen sensor that fiber tip is made as the ruthenium complex that will have the fluorescent quenching effect, be widely used in space, environment measuring, soil monitoring etc.
Phosphocholine is the main component of the outer phospholipid head part of biological cell membrane, the polymer that contains the phosphocholine group has been applied to bio-medical material and apparatus surface, can reduce the foreign body reaction that produces when contacting with body fluid such as blood, tear film and urine etc. effectively.The phosphocholine group is polar, and the existing positive charge of its intramolecule also has negative charge, and molecule is electroneutral generally.It has intensive hydrophilic, can reduce protein effectively in its surperficial reversible adhesion.The polymer of being reported at present that contains the phosphocholine group mainly by 2-methylacryoyloxyethyl-2 '-trimethylamine ethyl phosphonic acid ester inner salt (MPC) forms with other monomer copolymerizations, the MPC copolymer has been applied to the medical apparatus surface that cardiac stent, interposing catheter and hemodialysis membrane etc. and blood of human body directly contact, improve the blood compatibility of apparatus, reduce proteinic adhesion in blood coagulation and the blood.But also there is not this base polymer to be applied to the report of vivo implantation type electrochemiluminescence material at present.
Summary of the invention
The objective of the invention is to overcome the defective that present blood oxygen detects apparatus, provide a kind of at vivo real-time photo-sensitive blood oxygen sensor and preparation method thereof.
The present invention is at vivo real-time photo-sensitive blood oxygen sensor, and it is experienced film 2 by ordinary optic fibre 1 with the oxygen that is coated on optical fiber connector and constitutes.
Described blood oxygen is experienced film and is made up of highly sensitive oxygen electrochemiluminescence material and the polymer that contains the phospholipid group.This complex is applied to the optical fibers end, connects light source, used fluorescence filter disc, the photocell receiving device can assemble small-sized fluorescence partial pressure of oxygen analyzer.
The present invention combines the high degree of biocompatibility of phosphocholine polymer and anti-protein adhesion property and high sensitivity electrochemiluminescence material, makes the electrochemiluminescence oxygen sensor with stable against biological contamination usefulness, is used for the analyzing and testing of blood oxygen.
The present invention is the chemiluminescence that is excited by electrochemical reaction at vivo real-time photo-sensitive blood oxygen sensor, has high sensitivity, this highly sensitive electrochemiluminescence material is fixed to electrode or optical fiber surface, then can save mass expensive reagent, simplify the operation and apparatus structure, help enlarging the range of application of instrument.Compare with traditional oxygen instrument, it has in the body real-time continuous detects oxygen in the blood, long service life, and measuring range is wide, is swift in response good reproducibility, steady performance.
The present invention realizes by following preparation method and step:
1) oxygen electrochemiluminescence material is dissolved in certain solvent,
In the preferred version, the metal Ru complex is dissolved in the methanol, metal Ru complex/formaldehyde ratio is 4～5 mg/ml;
2) in above-mentioned solution, add the polymer solution that contains the phospholipid group, mix homogeneously;
In the preferred version, every milligram of metal Ru complex and 10 milligrams of copolymers are dissolved in the same solution, after the filtration, in gained solution, add entry, stir 1.5～3 microliters of water/10 milligram copolymer;
3) with the end of solution coat at optical fiber, heat treatment is 5 hours in 70 degree baking ovens, with solvent evaporates,
The oxygen that forms 0.2～0.3 millimeters thick is experienced film, is formed in vivo real-time photo-sensitive blood oxygen sensor.
The present invention be applicable to can be in solvent dissolved oxygen electrochemiluminescence material and phospholipid polyalcohol.Wherein highly sensitive electrochemiluminescence material comprises the metal Ru complex, metal osmium complex, metallic lead complex, metal platinum and palladium complex, rhenium metal complex and/or transition metal porphyrin complex.Wherein special preferable alloy ruthenium complex.
Among the present invention the employed polymer that contains the phospholipid group be 2-methylacryoyloxyethyl-2 '-trimethylamine ethyl phosphonic acid ester inner salt (MPC) contains the monomeric copolymer of polymerizable groups with other, this copolymerization system 2-methylacryoyloxyethyl-2 '-in trimethylamine ethyl phosphonic acid ester inner salt (MPC) and the following monomer one or more carry out free-radical polymerized obtaining: acrylic or methacrylic dialkylaminobenzoic acid (methyl, ethyl, propyl group, butyl, amyl group, hexyl, heptyl, octyl group, nonyl, decyl, dodecyl, cetyl, octadecyl) ester, acrylic or methacrylic acid hydroxy methacrylate, acrylic or methacrylic acid hydroxy propyl ester, acrylic or methacrylic acid glycol ester, acrylic or methacrylic acid glycol methyl ether ester, acrylic or methacrylic acid polyethylene glycol ester, acrylic or methacrylic acid polyethylene glycol methyl ether ester, vinyl pyrrolidone, vinylacetate, silane coupler such as γ-(methacryloxy) propyl trimethoxy silicane of containing two keys, or γ-(methacryloxy) propyl-triethoxysilicane.
Description of drawings
Fig. 1 is at the vivo real-time photo-sensitive blood oxygen sensor sketch map,
Wherein 1: optical fiber, 2: oxygen is experienced film.
Fig. 2 be synthetic ruthenium complex to the sensitivity and the repeatability of partial pressure of oxygen,
Wherein, be swift in response: less than reaching balance in 1 minute as can be seen to the partial pressure of oxygen sensitivity.
The specific embodiment
Embodiment 1:
30 gram MPC, 68 gram butyl methacrylates, 2 gram γ-(methacryloxy) propyl trimethoxy silicanes and 0.1 gram initiator A IBN are dissolved in the dehydrated alcohol, slowly feed argon deoxygenation in 1 hour.Place 70 ℃ of waters bath with thermostatic control then, stir reaction down 24 hours.After reaction finishes, solution is cooled to room temperature, purifies 2 times with a large amount of normal hexane precipitations; At room temperature with the precipitate vacuum drying collected 24 hours.Obtain containing copolymer 90 grams of phospholipid group.
0.1 gram tris (bipyridine) ruthenium is dissolved in 10 ml methanol, getting the above-mentioned copolymer that contains the phospholipid group of 0.4 gram is dissolved in the same solution, after the filtration, in gained solution, add 20 microliters of water, after stirring with the end of solution coat at optical fiber, heat treatment is 5 hours in 70 degree baking ovens, with solvent evaporates, promptly gets the stable against biological contamination Fibre Optical Sensor that can be used for measuring dissolved oxygen in blood or the rich in proteins solution.
Embodiment 2:
15 gram MPC, 10 gram metering system acid polyethylene glycol (molecular weight 360) methyl ether esters, 10 gram methacrylic acid glycol methyl ether esters, 63 gram lauryl methacrylates, 2 gram γ-(methacryloxy) propyl trimethoxy silicanes and 0.1 gram initiator A IBN are dissolved in dehydrated alcohol/oxolane (volume ratio 50/50) solution, slowly feed argon deoxygenation in 1 hour.Place 70 ℃ of waters bath with thermostatic control then, stir reaction down 24 hours.After reaction finishes, solution is cooled to room temperature, purifies 2 times with a large amount of normal hexane precipitations; At room temperature with the precipitate vacuum drying collected 24 hours.Obtain containing copolymer 92 grams of phospholipid group.
With 0.1 gram two (2,2 '-bipyridyl)-two chloro-two hydration rutheniums and phenanthroline imdazole derivatives are dissolved in 10 milliliters of ethanol/oxolane mixed solution, getting the above-mentioned copolymer that contains the phospholipid group of 0.4 gram is dissolved in the same solution, after the filtration, in gained solution, add 20 microliters of water, after stirring with the end of solution coat at optical fiber, heat treatment is 5 hours in 70 degree baking ovens, with solvent evaporates, promptly get the stable against biological contamination Fibre Optical Sensor that can be used for measuring dissolved oxygen in blood or the rich in proteins solution.
Embodiment illustrated and that discuss is only used for demonstrating use known for inventor best mode of the present invention to those skilled in the art in this description.Any content in the description all can not be thought limiting the scope of the invention.Can make amendment and do not exceed scope of the present invention above embodiment, by above explanation, this be conspicuous for those skilled in the art.Therefore it should be understood that in the scope of claims and equivalent thereof, can the mode different implement the present invention with above specific descriptions.
Claims (6)
1. one kind at vivo real-time photo-sensitive blood oxygen sensor, it is characterized in that experiencing film by ordinary optic fibre and the oxygen that is coated on optical fiber connector constitutes.
2. according to claim 1 at vivo real-time photo-sensitive blood oxygen sensor, it is characterized in that described oxygen experiences film and be made up of highly sensitive oxygen electrochemiluminescence material and the polymer that contains the phospholipid group, described highly sensitive oxygen electrochemiluminescence material is selected from the metal Ru complex, the metal osmium complex, the metallic lead complex, metal platinum and palladium complex, rhenium metal complex or transition metal porphyrin complex; The described polymer that contains the phospholipid group is that 2-methylacryoyloxyethyl-2 '-trimethylamine ethyl phosphonic acid ester inner salt (MPC) contains the monomeric copolymer of polymerizable groups with other.
3. according to claim 1 and 2 at vivo real-time photo-sensitive blood oxygen sensor, it is characterized in that described highly sensitive oxygen electrochemiluminescence material is the metal Ru complex.
4. according to claim 1 and 2 at vivo real-time photo-sensitive blood oxygen sensor, it is characterized in that described and 2-methylacryoyloxyethyl-2 '-monomer of trimethylamine ethyl phosphonic acid ester inner salt (MPC) copolymerization is an acrylic or methacrylic dialkylaminobenzoic acid (methyl, ethyl, propyl group, butyl, amyl group, hexyl, heptyl, octyl group, nonyl, decyl, dodecyl, cetyl, octadecyl) ester, acrylic or methacrylic acid hydroxy methacrylate, acrylic or methacrylic acid hydroxy propyl ester, acrylic or methacrylic acid glycol ester, acrylic or methacrylic acid glycol methyl ether ester, acrylic or methacrylic acid polyethylene glycol ester, acrylic or methacrylic acid polyethylene glycol methyl ether ester, vinyl pyrrolidone, vinylacetate contains wherein one or more of the silane coupler of two keys such as γ-(methacryloxy) propyl trimethoxy silicane or γ-(methacryloxy) propyl-triethoxysilicane.
5. according to claim 1 and 2 at vivo real-time photo-sensitive blood oxygen sensor, it is characterized in that described oxygen experiences film and prepare by following method:
1) oxygen electrochemiluminescence material is dissolved in certain solvent;
2) in above-mentioned solution, add the polymer solution that contains the phospholipid group, mix homogeneously;
3) with the end of solution coat at optical fiber, heat treatment is 5 hours in 70 degree baking ovens, and with solvent evaporates, the oxygen that forms 2～3 millimeters thick is experienced film, is formed in vivo real-time photo-sensitive blood oxygen sensor.
6. according to claim 5 at vivo real-time photo-sensitive blood oxygen sensor, in the wherein said step 1, oxygen electrochemiluminescence material metal Ru complex is dissolved in the methanol, metal Ru complex/methanol ratio is 6～10 mg/ml; In the step 2, every milligram of metal Ru complex and 10 milligrams of copolymers are dissolved in the same solution, after the filtration, in gained solution, add entry, 1.5～3 microliters of water/10 milligram copolymer.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200510030572 CN1947657A (en) | 2005-10-14 | 2005-10-14 | In-vivo real-time photo-sensitive blood oxygen sensor, and its making method |
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| CN 200510030572 CN1947657A (en) | 2005-10-14 | 2005-10-14 | In-vivo real-time photo-sensitive blood oxygen sensor, and its making method |
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| CN1947657A true CN1947657A (en) | 2007-04-18 |
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Open date: 20070418 |