Process for the manufacture of wholly microfabricated biosensors
First Claim
1. A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises:
- (a) applying a plurality of base sensors on a substrate wafer;
(b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less;
(c) applying a matrix, superimposed over at least a portion of said permselective layer and each of said base sensors, which matrix is selected from the group consisting of a photoformable proteinaceous material, a film-forming latex, and combinations thereof, and which is capable of incorporating a bioactive agent; and
(d) incorporating into said matrix an amount of said bioactive agent sufficient to selectively interact with a particular analyte species, to form a plurality of uniform wafer level microfabricated sensing devices.
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Abstract
An efficient method for the microfabrication of electronic devices which have been adapted for the analyses of biologically significant analyte species is described. The techniques of the present invention allow for close control over the dimensional features of the various components and layers established on a suitable substrate. Such control extends to those parts of the devices which incorporate the biological components which enable these devices to function as biological sensors. The materials and methods disclosed herein thus provide an effective means for the mass production of uniform wholly microfabricated biosensors. Various embodiments of the devices themselves are described herein which are especially suited for real time analyses of biological samples in a clinical setting. In particular, the present invention describes assays which can be performed using certain ligand/ligand receptor-based biosensor embodiments. The present invention also discloses a novel method for the electrochemical detection of particular analyte species of biological and physiological significance using an substrate/label signal generating pair which produces a change in the concentration of electroactive species selected from the group consisting of dioxygen and hydrogen peroxide.
279 Citations
51 Claims
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1. A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises:
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(a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; (c) applying a matrix, superimposed over at least a portion of said permselective layer and each of said base sensors, which matrix is selected from the group consisting of a photoformable proteinaceous material, a film-forming latex, and combinations thereof, and which is capable of incorporating a bioactive agent; and (d) incorporating into said matrix an amount of said bioactive agent sufficient to selectively interact with a particular analyte species, to form a plurality of uniform wafer level microfabricated sensing devices. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 50, 51)
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2. A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises:
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(a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer superimposed over at least a portion of each base sensor; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) a sufficient amount of a bioactive molecule, and (ii) a support matrix in which said bioactive molecule is incorporated, which matrix is formed from the group consisting of a photoformable .proteinaceous mixture, a film-forming latex, and combinations thereof to form a plurality of uniform wafer level microfabricated sensing devices.
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39. A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises:
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(a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) an amount of a bioactive agent, and (ii) a support matrix, in which said bioactive agent is incorporated, which matrix is a photoformable proteinaceous material, to form a plurality of uniform wafer level microfabricated sensing devices. - View Dependent Claims (41, 42, 43, 44, 45, 46, 47, 48, 49)
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40. A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises:
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(a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) an amount of bioactive agent sufficient to selectively interact with an analyte species, and (ii) a support matrix, in which said bioactive agent is incorporated, which matrix is formed from a film-forming latex, to form a plurality of uniform wafer level microfabricated sensing devices.
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Specification