Wholly microfabricated biosensors and process for the manufacture and use thereof
First Claim
1. A wafer level microfabricated biosensor comprising:
- (a) a base sensor;
(b) a permselective layer, superimposed over at least a portion of said base sensor, having a thickness sufficient to exclude substantially molecules with a molecular weight of about 120 or more while allowing the free permeation of molecules with a molecular weight of about 50 or less;
an(c) a biolayer superimposed over at least a portion of said permselective layer, comprising (i) a sufficient amount of a bioactive molecule capable of selectively interacting with a particular analyte species, and (ii) a support matrix in which said bioactive molecule is incorporated, which matrix is derived from the group consisting of a photoformable proteinaceous mixture, a film-forming latex, and combinations thereof and through which matrix said analyte species may freely permeate and interact with said bioactive molecule.
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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.
1240 Citations
51 Claims
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1. A wafer level microfabricated biosensor comprising:
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(a) a base sensor; (b) a permselective layer, superimposed over at least a portion of said base sensor, having a thickness sufficient to exclude substantially molecules with a molecular weight of about 120 or more while allowing the free permeation of molecules with a molecular weight of about 50 or less;
an(c) a biolayer superimposed over at least a portion of said permselective layer, comprising (i) a sufficient amount of a bioactive molecule capable of selectively interacting with a particular analyte species, and (ii) a support matrix in which said bioactive molecule is incorporated, which matrix is derived from the group consisting of a photoformable proteinaceous mixture, a film-forming latex, and combinations thereof and through which matrix said analyte species may freely permeate and interact with said bioactive molecule. - View Dependent Claims (2, 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, 35, 36, 37, 38, 44)
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33. A wafer level microfabricated biosensor comprising:
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(a) a base sensor; (b) a permselective layer, superimposed over at least a portion of said base sensor, having a thickness sufficient to exclude substantially molecules with a molecular weight of about 120 or more while allowing the free permeation of molecules with a molecular weight of about 50 or less; and (c) a biolayer superimposed over at least a portion of said permselective layer and said base sensor, comprising (i) a sufficient amount of a bioactive molecule capable of selectively interacting with a particular analyte species, and (ii) a support matrix derived from a photoformable proteinaceous mixture, in which said bioactive molecule is incorporated, and through which matrix said analyte species may freely permeate and interact with said bioactive molecule.
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34. A wafer level microfabricated biosensor comprising:
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(a) a base sensor; (b) a permselective layer, superimposed over at least a portion of said base sensor, having a thickness sufficient to exclude substantially molecules with a molecular weight of about 120 or more while allowing the free permeation of molecules with a molecular weight of about 50 or less; and (c) a biolayer superimposed over at least a portion of said permselective layer and said base sensor, comprising (i) a sufficient amount of a bioactive molecule capable of selectively interacting with a particular analyte species, and (ii) a support matrix derived from a film-forming latex, in which said bioactive molecule is incorporated, and through which matrix said analyte species may freely permeate and interact with said bioactive molecule.
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39. A wafer level microfabricated biosensor comprising:
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(a) a base sensor; (b) a permselective layer comprising a heat-treated film of a silane compound having the formula R'"'"'n Si(OR)4-n, in which n is 0, 1 or 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, said permselective layer being superimposed over at least a portion of said base sensor and having a thickness sufficient to exclude substantially molecules with a molecular weight of about 120 or more while allowing the free permeation of molecules with a molecular weight of about 50 or less; and(c) a topmost layer comprising a sufficient amount of an immobilized ligand receptor. - View Dependent Claims (40, 43)
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41. A wafer level microfabricated biosensor comprising:
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(a) a base sensor; (b) a permselective layer comprising a polymer film, superimposed over at least a portion of said base sensor and having a thickness sufficient to exclude substantially molecules with a molecular weight of about 120 or more while allowing the free permeation of molecules with a molecular weight of about 50 or less; (c) a photoresist layer comprising a photoformable proteinaceous mixture, superimposed over a substantial portion of said permselective layer; and (d) a topmost layer comprising a sufficient amount of an immobilized ligand receptor. - View Dependent Claims (42)
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45. A biolayer sensitive to a particular analyte species comprising:
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(a) a sufficient amount of a bioactive molecule capable of selectively interacting with a particular analyte species; and (b) a support matrix in which said bioactive molecule is incorporated, which matrix is derived from the group consisting of a photoformable proteinaceous mixture, a film-forming latex, and combinations thereof and through which said analyte species may freely permeate and interact with said bioactive molecule.
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46. A solid object having an outer surface, an inner surface, or both, over at least a portion of which surface is established a biolayer sensitive to a particular analyte species comprising:
- (i) a sufficient amount of a bioactive molecule capable of selectively interacting with a particular analyte species; and
(ii) a support matrix in which said bioactive molecule is incorporated, which matrix is derived from the group consisting of a photoformable proteinaceous mixture, a film-forming latex, and combinations thereof and through which said analyte species may freely permeate and interact with said bioactive molecule. - View Dependent Claims (47, 48)
- (i) a sufficient amount of a bioactive molecule capable of selectively interacting with a particular analyte species; and
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49. A permselective layer comprising a heat-treated film of a silane compound having a formula R'"'"'n Si(OR)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 lower alkyl radical comprising 1-4 carbon atoms,said layer having a thickness sufficient to exclude substantially molecules with a molecular weight of about 120 or more while allowing the free permeation of molecules with a molecular weight of about 50 or less.
- R'"'"' is a hydrocarbon radical comprising 3-12 carbon atoms; and
- 50. An analyte attenuation layer comprising a film of a siloxane-nonsiloxane copolymer and which film has a thickness sufficient to attenuate the transport therethrough of analyte species having a molecular weight of about 120 or more.
Specification