# US 5,212,050 A · Method of forming a permselective layer

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 5,212,050 A
- Document ID: US5212050A
- Status: Granted
- Kind: A
- Application number: 07/568,441
- Filed: 1990-08-15
- Granted: 1993-05-18
- Earliest claimed: 1988-11-14
- Inventors: Randall M. Mier; Sylvia Piznik; Imants R. Lauks; Graham Davis
- Web page: https://patentgrep.com/patent/US5212050A

## CPC

- B01L 3/0268: {using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries}
- B01L 3/502707: {characterised by the manufacture of the container or its components}
- C12Q 1/001: {Enzyme electrodes}
- G01N 33/5438: {Electrodes}
- G01N 35/0099: {comprising robots or similar manipulators (robots per se B25J)}
- B01L 3/5088: {confining liquids at a location by surface tension, e.g. virtual wells on plates, wires (B01L3/50857 takes precedence)}
- B01L 2200/12: Specific details about manufacturing devices
- B01L 2300/0636: Integrated biosensor, microarrays
- B01L 2300/0645: Electrodes
- B01L 2300/0877: Flow chambers
- G01N 35/109: {with two horizontal degrees of freedom}
- G01N 2035/00059: {vacuum chucks}
- G01N 2035/00237: {Handling microquantities of analyte, e.g. microvalves, capillary networks}
- G01N 2035/00455: {Controlling humidity in analyser}
- G01N 2035/00534: {Mixing by a special element, e.g. stirrer}
- G01N 2035/1034: {Transferring microquantities of liquid}
- G01N 2035/1076: {plurality or independently movable heads}
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A method of forming a permselective layer on preselected areas of a substantially planar sensing device is disclosed. The claimed method includes establishing and confining a liquid film, derived from a silane compound mixed in a suitable solvent, within a predetermined area of the sensing device. The process relates to photolithographic imaging and developing methods coupled to a film-curing step that provides a patterned permselective layer having the desired semipermeable characteristics.

## Claims

### Claim 1

A method for forming a permselective layer on preselected areas of a substantially planar sensing device which comprises:
(a) establishing a photoresist layer on a substantially planar sensing device;
(b) processing said photoresist layer using photolithographic techniques to expose preselected areas of said sensing device;
(c) establishing at least one film comprising a silane compound mixed with a suitable solvent on the sensing device of step (b), said compound having the formula R'.sub.n Si(OR).sub.4-n, in which n is an integer selected from the group consisting of 0, 1, and 2; R' is a hydrocarbon radical comprising 3-12 carbon atoms; and R is a hydrogen radical or a lower alkyl radical comprising 1-4 carbon atoms; and
(d) heating said film to a temperature of at least about 100.degree. C. for a period of time effective to form a permselective layer having a thickness of about 1 to about 1000 nm sufficient to provide said permselective layer with the desired semipermeable properties in which molecules having about a first preselected molecular weight or above are substantially precluded from permeating through said permselective layer, while molecules having about a second preselected molecular weight or below may effectively permeate therethrough; and
(e) removing the underlying photoresist layer and the permselective layer overlaid thereover from all except the preselected areas of said sensing device.

### Claim 2 (depends on 1)

The method of claim 1 which further comprises heating said device of step (e) to a temperature in excess of about 150.degree. C. to about 250.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 3 (depends on 1)

The method of claim 1 which further comprises heating said device of step (e) to a temperature in the range of about 150.degree. C. to about 250.degree. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 4 (depends on 1)

The method of claim 1 in which said film is heated in step (d) to a temperature or about 160.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 5

A method of forming a permselective layer on preselected areas of a substantially planar sensing device which comprises:
(a) establishing at least one film comprising a silane compound mixed with a suitable solvent on a substantially planar sensing device, said compound having the formula R'.sub.n Si(OR).sub.4-n, in which n is an integer selected from the group consisting of 0, 1 and 2; R' is a hydrocarbon radical comprising 3-12 carbon atoms; and R is a hydrogen radical or a lower alkyl radical comprising 1-4 carbon atoms; and
(b) heating said film to a temperature of at least about 100.degree. C. for a period of time effective to form a permselective layer having a thickness of about 1 to about 1,000 nm sufficient to provide said permselective layer with the desired semipermeable properties in which molecules having about a first preselected molecular weight or above are substantially precluded from permeating through said permselective layer, while molecules having about a second preselected molecular weight or below may effectively permeate therethrough;
(c) establishing a photoresist layer on said permselective layer;
(d) processing said photoresist layer using photolithographic techniques such that a proportion of the underlying permselective layer becomes exposed and subject to further processing, while those preselected areas of the device retain a protective cap of photoresist material;
(e) removing said exposed permselective layer; and
(f) removing said protective photoresist layer to leave a permselective layer over preselected areas of said device.

### Claim 6 (depends on 5)

The method of claim 5 in which step (e) comprises contacting said permselective layer with an etchant selected from the group consisting of dry agents, wet agents, and combinations thereof.

### Claim 7 (depends on 5)

The method of claim 5 in which step (e) comprises contacting said permselective layer with an etchant selected from the group consisting of an oxygen plasma, a 0.0001-0.01 weight percent solution of hydrofluoric acid in a protic solvent and combinations thereof.

### Claim 8 (depends on 5)

The method of claim 5 which further comprises heating said device of step (f) to a temperature in excess of about 150.degree. C. to about 250.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 9 (depends on 5)

The method of claim 5 which further comprises heating said device of step (f) to a temperature in the range of about 150.degree. C. to about 250.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 10 (depends on 5)

The method of claim 5 in which said film is heated in step (b) to a temperature of about 160.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 11 (depends on 1, 5)

The method of claim 1 or 5 in which the thickness of said permselective layer is such that said permselective layer is permeable to molecules having a molecular weight of about 50 or less, yet substantially impermeable to molecules having a molecular weight of about 120 or more.

### Claim 12 (depends on 1, 5)

The method of claim 1 or 5 in which the thickness of said permselective layer is in the range of about 20 to about 500 .ANG..

### Claim 13 (depends on 1, 5)

The method of claim 1 or 5 in which said permselective layer is further characterized as: (i) having a thickness in the range of about 50 to about 100 .ANG.; (ii) being permeable to molecules selected from the group consisting of dioxygen and hydrogen peroxide; and (iii) being substantially impermeable to molecules selected from the group consisting of uric acid, ascorbic acid, salicylic acid, 2-(p-isobutylphenyl)propionic acid, cysteine, 4-acetamidophenol, and physiological salts thereof.

### Claim 14 (depends on 1, 5)

The method of claim 1 or 5 in which said sensing device is an amperometric electrochemical sensor.

### Claim 15 (depends on 1, 5)

The method of claim 1 or 5 in which said solvent is comprised of an aqueous solution of a nonionic surfactant present in a concentration of about 0.005 to about 0.2 percent by weight of said aqueous solution.

### Claim 16 (depends on 1, 5)

The method of claim 1 or 5 in which said solvent is a water-immiscible organic solvent.

### Claim 17 (depends on 1, 5)

The method of claim 1 or 5 in which said solvent is a chlorinated organic solvent selected from the group consisting of methylene chloride, trichloroethane, tetrachloroethane, chlorobenzene, dichlorobenzene, and mixtures thereof.

### Claim 18 (depends on 1, 5)

The method of claim 1 or 5 in which said film is established by a means selected from the group consisting of spin-coating, dip-coating, spray-coating, and microdispensing.

### Claim 19 (depends on 1, 5)

The method of claim 1 or 5 in which said film is heated to a temperature in the range of about 100.degree. C. and about 250.degree. C. for a period of at least about 5 minutes.

### Claim 20 (depends on 1, 5)

The method of claim 1 or 5 in which said silane compound is N-(2-aminoethyl)-3-aminopropyltrimethoxysilane.

### Claim 21 (depends on 1, 5)

The method of claim 1 or 5 in which said film is established by a microdispensing system.

### Claim 22 (depends on 1, 5)

The method of claim 1 or 5 in which different silane films are established.

### Claim 23 (depends on 1, 5)

The method of claim 1 or 5 in which said preselected areas encompass the indicator electrode of an amperometric electrochemical sensor.

### Claim 24 (depends on 1, 5)

The method of claim 1 or 5 in which said photoresist layer is comprised of a positive photoresist and said processing step comprises (i) irradiating said photoresist layer through a mask, and (ii) developing the irradiated photoresist layer to expose preselected areas of said sensing device.

### Claim 25 (depends on 24)

The method of claim 24 in which said developing step comprises contacting said irradiated photoresist layer with a lower alkyl acetate ester solvent.

### Claim 26 (depends on 1, 5)

The method of claim 1 or 5 in which step (e) or step (f), respectively, comprises exposing said device to a solvent capable of dislodging or dissolving said photoresist layer.

### Claim 27 (depends on 1, 5)

The method of claim 1 or 5 in which said hydrocarbon radical further comprises at least one heteroatom selected from the group consisting of oxygen, nitrogen, phosphorus, sulfur and stable combinations thereof.

### Claim 28 (depends on 1, 5)

The method of claim 1 or 5 in which n is equal to 1.

### Claim 29

A method for forming a patterned semipermeable solid film onto a planar sensing device which comprises:
(a) establishing a layer of a resist material over a planar sensing device;
(b) subjecting the layer of step (a) to radiant energy through a photolithographic mask and developing the resultant irradiated layer such that preselected area of said device become exposed and subject to further processing;
(c) establishing a liquid film over the patterned layer of step (b), which liquid film comprises an organosilicon compound mixed with a suitable solvent, said compound having the formula R'Si(OR).sub.3 in which R' is a hydrocarbon radical comprising 3-12 carbon atoms and R is a lower alkyl radical comprising 1-4 carbon atoms;
(d) heating the liquid film of step (c) to a temperature of at least about 100.degree. C. for a period of time effective to form a solid film having a thickness of about 20 to about 500 .ANG. sufficient to provide said solid film with the desired semipermeable properties in which molecules having molecular weights above a given threshold can be effectively excluded from entering and diffusing through said solid film, while allowing the free passage and diffusion of lower molecular weight electroactive species; and
(e) exposing the solid film of step (d) to a solvent capable of dislodging the underlying layer of resist material and allowing said solid film to separate from said device, leaving a patterned semipermeable solid film over the preselected areas of said device.

### Claim 30 (depends on 29)

The method of claim 29 which further comprises heating said device of step (e) to a temperature in the range of about 150.degree. to about 250.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 31 (depends on 29)

The method of claim 29 in which said film is heated in step (d) to a temperature of 170.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 32

A method of forming a patterned semipermeable solid film onto a planar sensing device which comprises:
(a) establishing a liquid film over a planar sensing device, which liquid film comprises an organosilicon compound mixed with a suitable solvent, said compound having the formula R'Si(OR).sub.3 in which R' is a hydrocarbon radical comprising 3-12 carbon atoms and R is a lower alkyl radical comprising 1-4 carbon atoms;
(b) heating the liquid film of step (a) to a temperature of at least about 100.degree. C. for a period of time effective to form a solid film having a thickness of about 20 to about 500 .ANG. sufficient to provide said solid form with the desired semipermeable properties in which molecules having molecular weights above a given threshold can be effectively excluded from entering and diffusing through said solid film, while allowing the free passage and diffusion of lower molecular weight electroactive species;
(c) establishing a layer of a resist material over the solid film of step (b);
(d) subjecting the layer of step (c) to radiant energy through a photolithographic mask and developing the resultant irradiated layer such that a substantial proportion of the underlying solid film becomes exposed and subject to further processing, while those preselected areas of the device retain a protective cap of resist material;
(e) subjecting the exposed solid film of step (d) to an etchant for a length of time sufficient to remove substantially all of said exposed solid film; and semipermeable solid film over the preselected areas of said device.

### Claim 33 (depends on 32)

The method of claim 32 in which said etchant is selected from the group consisting of dry and wet agents.

### Claim 34 (depends on 32)

The method of claim 32 in which said etchant is selected from the group consisting of an oxygen plasma and a 0.0001-0.01 weight percent solution of hydrofluoric acid in a protic solvent.

### Claim 35 (depends on 32)

The method of claim 32 which further comprises heating said device of step (f) to a temperature in the range of about 150.degree. C. to about 250.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 36 (depends on 32)

The method of claim 32 in which said film is heated in step (b) to a temperature of 170.degree. C. to maximize the indicator electrode response toward the oxidation of hydrogen peroxide.

### Claim 37 (depends on 29, 32)

The method of claim 29 or 32 in which the thickness of said solid film is such that molecules having a molecular weight of about 120 or more are substantially precluded from permeating through said solid film, while molecules having a molecular weight of about 50 or less may diffuse through effectively.

### Claim 38 (depends on 29, 32)

The method of claim 29 or 32 in which the thickness of said solid film is in the range of about 20 to about 500 .ANG..

### Claim 39 (depends on 21, 32)

The method of claim 21 or 32 in which said solid film is further characterized as: (i) having a thickness in the range of about 50 to about 100 .ANG.; (ii) being permeable to molecules selected from the group consisting of dioxygen and hydrogen peroxide; and (iii) being substantially impermeable to molecules selected from the group consisting of uric acid, ascorbic acid, salicylic acid, 2-(p-isobutylphenyl)proprionic acid, cysteine, 4-acetamidophenol, and physiological salts thereof.

### Claim 40 (depends on 29, 32)

The method of claim 29 or 32 in which said planar sensing device is an amperometric electrochemical sensor manufactured by thin film technology.

### Claim 41 (depends on 29, 32)

The method of claim 29 or 32 in which said solvent is comprised of an aqueous solution of a nonionic surfactant present in a concentration of about 0.005 to about 0.2 percent by weight of said aqueous solution.

### Claim 42 (depends on 29, 32)

The method of claim 29 or 32 in which said solvent is a water-immiscible organic solvent.

### Claim 43 (depends on 29, 32)

The method of claim 29 or 32 in which said liquid film is established on said planar sensing device by a means selected from the group consisting of spin-coating, dip-coating, spray-coating, and microdispensing.

### Claim 44 (depends on 29, 32)

The method of claim 29 or 32 in which said liquid is heated to a temperature in the range of about 100.degree. C. to about 250.degree. C. for a period of at least about 5 minutes.

### Claim 45 (depends on 29, 32)

The method of claim 29 or 32 in which said hydrocarbon radical further comprises at least one heteroatom selected from the group consisting of oxygen, nitrogen, phosphorus, sulfur, and stable combinations thereof.

### Claim 46 (depends on 29, 32)

The method of claim 29 or 32 in which said organosilicon compound is N-)2-aminoethyl)-3-aminopropyltrimethoxysilane.

### Claim 47 (depends on 1, 5, 29, 32)

The method of claim 1, 5, 29 or 32 in which the thickness of said permselective layer is in the range of about 20 to about 200 .ANG..

### Claim 48 (depends on 1, 5, 29, 32)

The method of claim 1, 5, 29 or 32 in which the thickness of said permselective layer is in the range of about 50 to about 100 .ANG..