EP0527210A1 - Solid state ion sensor with polyurethane membrane - Google Patents
Solid state ion sensor with polyurethane membraneInfo
- Publication number
- EP0527210A1 EP0527210A1 EP91910905A EP91910905A EP0527210A1 EP 0527210 A1 EP0527210 A1 EP 0527210A1 EP 91910905 A EP91910905 A EP 91910905A EP 91910905 A EP91910905 A EP 91910905A EP 0527210 A1 EP0527210 A1 EP 0527210A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- ionophore
- polyurethane
- ment
- integrated circuit
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/333—Ion-selective electrodes or membranes
Definitions
- This invention relates generally to devices and systems for measuring concentrations of ions, chemicals, biological materials, and reaction products, and more particularly, to a solid state device which employs a polyurethane matrix, having electrochemical properties comparable in quality to conventional PVC membranes, as the substance-sensitive membrane, and wherein the polyurethane membrane exhibits excellent adhesion to the Si 3 N surface of solid state sensors.
- solid state ion sensors are of interest in industrial and medical applications as replacements for traditional ion-selective electrodes. These sensors make possible new direct-monitoring applications. There is a need, however, for improved membrane adhesion, as such would be benefi ⁇ cial, not only to all users of solid-state chemical sensors, but particularly those interested in long-term monitoring.
- solid-state ion sensors can be divided into industrial and medical applica ⁇ tions.
- Industrial uses include, for example, the monitor ⁇ ing of treated or waste water for hardness or pollutants; on-line analysis of industrial chemicals, foodstuffs, and medicines; and low cost analytical instruments.
- Medical applications include the monitoring of electrolytes, blood gases, and metabolic substrates, both for biochemical control systems and for patient monitoring or diagnostics.
- solid state ion sensors which can achieve the needs of industrial and medical monitoring for very long periods of time.
- Silicon-based chemical sensors often use ionophore-doped polymeric membranes as transduc ⁇ ers because of their excellent selectivity toward the ion of interest, the wide range of ions for which ionophores are available, and because they can borrow from ongoing developments in ion-selective electrode technology.
- PVC poly(vinylchloride)
- One of the primary causes of failure in conventional microsensors has been poor adhesion of the organic membrane to the chip surface. This leads to the formation of electrolyte shunts around the membrane, rendering the membrane inoperative.
- Others in the prior art have endeavored to improve membrane adhesion such as by the use of a polyimide suspended mesh, modification of PVC for binding to hydrox- yl-bearing surfaces, and mechanical attachment of the membrane. These methods have tended to improve adhesion of the membrane, but generally have resulted in either inferior electrochemical performance when compared to PVC or added processing complexity.
- a permselective membrane which exhibits good electrochemical properties, preferably at least as good as traditional PVC membranes, but which exhibits excellent adhesion to the Si 3 N 4 surface of solid state sensors.
- an object of this invention to provide a substance-sensitive solid state sensor which has an extended lifetime. It is another object of this invention to provide a substance-sensitive membrane system for a solid state sensor which is possessed of excellent electrochemical properties.
- a still further object of this invention is to provide a substance-sensitive membrane for use in a solid state sensor, wherein the membrane exhibits good adhesion to Si0 2 surfaces.
- An additional object of this invention is to provide a substance-sensitive membrane for use in a solid state sensor, wherein the membrane exhibits good adhesion to Si 3 N 4 surfaces.
- Yet another object of this invention is to provide a substance-sensitive membrane for use in a solid state sensor, wherein the membrane exhibits a reduced electrical resistance characteristic and thereby yields reduced electrical noise for the sensor.
- Another object of this invention is to provide a sub ⁇ stance-sensitive membrane for use in a solid state sensor, wherein the membrane exhibits a reduced tendency to adsorb protein.
- a yet further object of this invention is to provide a substance-sensitive membrane for use in a solid state sensor, wherein the membrane exhibits a reduced tendency to cause blood clotting.
- the integrated circuit sensor is provided with an input electrode formed of a conductive material in the vicinity of a region formed of a silicon- based semiconductor material, and a peirmselective membrane having a predetermined electrochemical property and formed of a polyurethane-based compound.
- the silicon-based compound is arranged to be in adherence with the polyur- ethane-based semiconductor material, and in electrical communication with the input electrode. In this manner, a voltage responsive to the alectrochemical property is produced at the input electrode.
- the permselective membrane is formed of a hydroxylated copolymer poly(vinylchloride / vinyl acetate / vinyl alcohol) (PVC/Ac/Al) (80/5/15 wt.%) with polyurethane, dissolved in THF, to form a polyurethane mixture.
- PVC/Ac/Al hydroxylated copolymer poly(vinylchloride / vinyl acetate / vinyl alcohol)
- An ionophore which may be responsive to ammonium, potassium, or any of several other chemicals or biological substances, is also mixed in with the polyurethane mixture.
- the sensors may be made responsive to other molecules through addition of bioactive agents, such as an enzyme, an immunochemical, a bacteria, and a virus.
- a plasticizer is also added.
- a substance-sensitive membrane is formed by the process of: first mixing an ionophore into a hydroxylated copoly ⁇ mer poly(vinylchloride / vinyl acetate / vinyl alcohol) (PVC/Ac/Al) (80/5/15 wt.%) with polyurethane, dissolved in THF, to form a polyurethane mixture; second mixing into said polyurethane mixture an ionophore; and third mixing into said polyurethane mixture a plasti ⁇ cizer.
- the further step of depositing the mixture onto a substrate In other embodiments, the mixture may be solvent cast.
- the ionophore may be, for example, an ammonium ionophore a potassium ionophore.
- the ionophore is present in a proportion of
- Fig. 1 is a graphical representation which illustrates the response of the ammonium-selective membranes.
- Fig. 2 shows the response of the potassium-selective membranes, including a measurement in blood serum
- Fig. 3 is a graphical representation which illustrates the result of blood clot tests
- Fig. 4 is a graphical representation of typical nitrophenylate calibration curves
- Fig. 5 is a graphical representation of a nitrophenol phosphate substrate response
- Fig. 6 is a substrate calibration curve for p-Nitro- phenyl phosphate.
- the present invention has been made by the inventors herein in the form of polyurethane-matrix membranes selective to potassium and ammonium.
- Such membranes exhibit good electrochemical properties and superb adhesion to silicon nitride.
- the highly beneficial adhesion characteristic was accomplished by using 20 wt. % hydroxy ⁇ lated PVC, which can be processed in the solvent tetra- hydrofuran (THF) .
- THF solvent tetra- hydrofuran
- This polyurethane material exhibits extremely high bond strength to a wide range of substrates, including Si 3 N 4 .
- the resulting polyurethane membrane exhibits reduced protein adsorption and blood clotting.
- the following table compares the electrochemical properties of four different membrane types toward potassi ⁇ um and ammonium.
- the polyurethane membrane is seen to have a comparable performance to PVC membranes, with even better slopes and detection limits.
- these polyur- ethane / hydroxylated PVC membranes have strong adhesion to glass and Si 3 N 4 , even without silanizing agents.
- 'Potassium and ammonium selective membranes are doped with 1% valinomy- cin and nonactin, respectively.
- the balance of the membrane is DOA (bis (2-ethylhexyl) adipate plasticizer.
- Electrochemical performance is excellent in either case, but adhesion is much better when (PVC/Ac/Al) is used.
- Fig. 1 is a graphical representation which illustrates the response of the ammonium- selective membranes.
- Fig. 2 shows the response of the potassium-selective membrane, including a measurement in blood serum. It is evident from these figures that the polyurethane membranes are usable in a wide variety of monitoring situations.
- Polyurethane has excellent biocompatibility, an important feature for many solid-state sensors. Blood tests were performed using glass tubes coated with various membrane types. Fresh human blood was brought into contact with the membranes by tilting the tubes every 60 seconds until clots formed. As shown in Fig. 3, the polymer coated tubes had longer clotting times than the glass tubes.
- Membrane adhesion is significant because it is one of the properties which determines the lifetime of solid state chemical sensors.
- the well-known "Scotch tape test” was employed. The results of this testing process is shown below in tabular form in Table 2.
- nitrophenolate-sensitive base membrane was prepared by incorporating tetraheptylammonium bromide as the ionophore.
- Typical nitrophenolate calibration curves for the base membrane, before and after enzyme immobiliza ⁇ tion, are shown in Fig. 4.
- nitrophenyl phosphate thealkalinephosphatase-immobilized sensor responded to enzymatically-produced nitrophenylate on the surface of the base sensing membrane, as shown in Fig. 5.
- Fig. 5 is a graphical representation of a nitroph- enol phosphate substrate response.
- Fig. 6 is a substrate calibration curve for p-Nitrophenyl Phosphate.
- the membrane could be applied, including dipping, casting, spin-coating, screen printing, etc.
- innumerable slight variations in the formulas could result in useful membranes.
- the simplest membranes are those containing ionophore to a specific ion.
- Such membranes should also be used in conjunction with, or incorporate in the membrane matrix, a bioactive agent, such as an enzyme, an immunochemical, a bacteria, etc.
- a bioactive agent such as an enzyme, an immunochemical, a bacteria, etc.
- the membranes can be made specific to more complex chemicals.
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Manufacture Of Macromolecular Shaped Articles (AREA)
- Investigating Or Analyzing Materials By The Use Of Fluid Adsorption Or Reactions (AREA)
Abstract
On utilise une matrice de polyuréthane afin de former une membrane sensible à une substance, laquelle est particulièrement adaptée pour être installée sur un détecteur à semi-conducteurs. Le ionophore peut être un ionophore de potassium, un ionophore d'ammonium, ou on peut coupler tout autre ionophore à la molécule d'intérêt par l'intermédiaire d'un agent bioactif tel qu'une enzyme, un agent immunochimique, une bactérie, un anticorps, un virus ou un antigène. La membrane obtenue sensible à une substance possède des propriétés électrochimiques supérieures à celles de membranes en PVC classiques, et elles présentent une adhérence sensiblement supérieure à des verres ainsi qu'à des matèriaux de substrat à semi-conducteurs. L'adhérence améliorée prolonge la durée de vie des détecteurs et empêche la formation de dérivations d'électrolytes dont on sait qu'elles rendent les détecteurs à semi-conducteurs inopérants.A polyurethane matrix is used to form a substance-sensitive membrane, which is particularly suitable for installation on a semiconductor detector. The ionophore can be a potassium ionophore, an ammonium ionophore, or any other ionophore can be coupled to the molecule of interest via a bioactive agent such as an enzyme, an immunochemical agent, a bacterium, an antibody, virus or antigen. The substance-sensitive membrane obtained has electrochemical properties superior to those of conventional PVC membranes, and they exhibit significantly greater adhesion to glasses as well as to semiconductor substrate materials. The improved adhesion extends the life of the detectors and prevents the formation of electrolyte leads which are known to render solid state detectors inoperative.
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US51765190A | 1990-05-02 | 1990-05-02 | |
US517651 | 1990-05-02 | ||
PCT/US1991/003024 WO1991017432A1 (en) | 1990-05-02 | 1991-05-02 | Solid state ion sensor with polyurethane membrane |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0527210A1 true EP0527210A1 (en) | 1993-02-17 |
EP0527210A4 EP0527210A4 (en) | 1994-09-21 |
Family
ID=24060663
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19910910905 Withdrawn EP0527210A4 (en) | 1990-05-02 | 1991-05-02 | Solid state ion sensor with polyurethane membrane |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0527210A4 (en) |
JP (1) | JPH05506938A (en) |
AU (1) | AU671253B2 (en) |
CA (1) | CA2081914A1 (en) |
WO (1) | WO1991017432A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993004359A1 (en) * | 1991-08-20 | 1993-03-04 | University Of Michigan | Batch deposition of polymeric ion sensor membranes |
PL316132A1 (en) * | 1994-03-25 | 1996-12-23 | Ciba Geigy Ag | Optical sensor for determination of ions |
KR100349000B1 (en) * | 1998-07-09 | 2003-03-26 | 주식회사 아이센스 | Manufacturing method of biosensor using hydrophilic polyurethane |
FR3103279B1 (en) | 2019-11-18 | 2021-10-08 | Commissariat Energie Atomique | METHOD OF MANUFACTURING A POLYMERIC MEMBRANE FOR THE POTENTIOMETRIC DETECTION OF AN ANALYTE PRESENT IN A FLUID |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4505800A (en) * | 1983-05-20 | 1985-03-19 | Eastman Kodak Company | Sodium-selective compositions and electrodes containing same |
US4608149A (en) * | 1983-06-20 | 1986-08-26 | Eastman Kodak Company | Potassium ion-selective compositions and electrodes containing same |
US4504368A (en) * | 1983-07-18 | 1985-03-12 | Eastman Kodak Company | Alkali metal ion-selective compositions and elements and a method of using same |
US4508613A (en) * | 1983-12-19 | 1985-04-02 | Gould Inc. | Miniaturized potassium ion sensor |
GB8528794D0 (en) * | 1985-11-22 | 1985-12-24 | Emi Plc Thorn | Buffer compensation in enzyme |
EP0235470B1 (en) * | 1986-01-24 | 1992-11-11 | TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION | Ion-sensitive fet sensor |
US4871442A (en) * | 1986-05-01 | 1989-10-03 | Terumo Corporation | Ion sensor |
NL8602242A (en) * | 1986-09-05 | 1988-04-05 | Stichting Ct Voor Micro Elektr | METHOD FOR MANUFACTURING A REFET OR A CHEMFET, AND THE MANUFACTURED REFET OR CHEMFET |
US4889612A (en) * | 1987-05-22 | 1989-12-26 | Abbott Laboratories | Ion-selective electrode having a non-metal sensing element |
-
1991
- 1991-05-02 CA CA002081914A patent/CA2081914A1/en not_active Abandoned
- 1991-05-02 JP JP91510811A patent/JPH05506938A/en active Pending
- 1991-05-02 AU AU80811/91A patent/AU671253B2/en not_active Expired - Fee Related
- 1991-05-02 WO PCT/US1991/003024 patent/WO1991017432A1/en not_active Application Discontinuation
- 1991-05-02 EP EP19910910905 patent/EP0527210A4/en not_active Withdrawn
Non-Patent Citations (2)
Title |
---|
No further relevant documents disclosed * |
See also references of WO9117432A1 * |
Also Published As
Publication number | Publication date |
---|---|
EP0527210A4 (en) | 1994-09-21 |
JPH05506938A (en) | 1993-10-07 |
AU8081191A (en) | 1991-11-27 |
AU671253B2 (en) | 1996-08-22 |
WO1991017432A1 (en) | 1991-11-14 |
CA2081914A1 (en) | 1991-11-03 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
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Effective date: 19921030 |
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Effective date: 19951228 |
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RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: THE UNIVERSITY OF MICHIGAN |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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18D | Application deemed to be withdrawn |
Effective date: 19970308 |