Microelectronic system and method of use and fabrication
First Claim
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1. A microelectronic system, wherein the microelectronic system includes a reaction region, the system comprising:
- a plurality of micro-locations distributed in the reaction region, wherein each micro-location comprises;
a first electrode disposed in a center of the micro-location;
a second electrode surrounding the first electrode with a distance, thus enclosing a space, wherein the second electrode is electrically insulated from the first electrode without loaded fluid;
an attachment layer coupled to a surface of the first electrode;
a plurality of binding entities coupled the attachment layer, wherein the binding entities are immobilized onto the surface of the first electrode through the attachment layer; and
a permeation layer for supporting the binding entities ,wherein the second electrodes isolate the first electrodes, acting as isolating walls, and wherein the space enclosed by the second electrode can hold loaded fluid;
a retaining wall around the reaction region;
a plurality of contact pads disposed outside the reaction region and surrounding the reaction region, for electrical operation;
a connective circuitry for connecting the first electrodes in the micro-locations and the contact pads;
an insulating layer for isolating the micro-locations and the connective circuitry, wherein the micro-locations are disposed on a first surface of the insulating layer and using the insulating layer as a base for the micro-locations, while a second surface of the insulating, opposite to the first surface, is attached to the connective circuitry; and
a cap layer over the micro-locations for sealing the micro-locations.
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Abstract
The invention provides a microelectronic system, which can actively carry out and control molecular biological reactions in microscopic formats. The microelectronic system is accomplished by using electrochemical detection for bulge sites in binding pairs, in order to enhance sensitivity without marking the probe with reporter groups. Together with electrical stringency control, the method can be fully automated with minimum sample preparation. The present invention is especially useful for diagnosing base pair mismatches in target sequences by using specific metal complexes for detection.
14 Citations
35 Claims
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1. A microelectronic system, wherein the microelectronic system includes a reaction region, the system comprising:
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a plurality of micro-locations distributed in the reaction region, wherein each micro-location comprises;
a first electrode disposed in a center of the micro-location;
a second electrode surrounding the first electrode with a distance, thus enclosing a space, wherein the second electrode is electrically insulated from the first electrode without loaded fluid;
an attachment layer coupled to a surface of the first electrode;
a plurality of binding entities coupled the attachment layer, wherein the binding entities are immobilized onto the surface of the first electrode through the attachment layer; and
a permeation layer for supporting the binding entities ,wherein the second electrodes isolate the first electrodes, acting as isolating walls, and wherein the space enclosed by the second electrode can hold loaded fluid;
a retaining wall around the reaction region;
a plurality of contact pads disposed outside the reaction region and surrounding the reaction region, for electrical operation;
a connective circuitry for connecting the first electrodes in the micro-locations and the contact pads;
an insulating layer for isolating the micro-locations and the connective circuitry, wherein the micro-locations are disposed on a first surface of the insulating layer and using the insulating layer as a base for the micro-locations, while a second surface of the insulating, opposite to the first surface, is attached to the connective circuitry; and
a cap layer over the micro-locations for sealing the micro-locations. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 29, 30, 31, 32, 33, 34, 35)
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15. A method for fabricating a microelectronic system, compatible with electrochemical detection, the method comprising:
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providing a three-layered structure, wherein the three-layered structure comprises a first layer, a second layer and a third layer between the first and second layers stacked together, and wherein the first layer has a central reaction region and a outer region surrounding the central reaction region;
forming a first patterned photoresist layer and a second patterned photoresist layer respectively on the first layer and the second layer;
patterning the first layer to form a plurality of holes in the central reaction region and form a plurality of blocks in the outer region, wherein the remained portion of the first layer in the central reaction region serves as a electrode;
patterning the second layer to form a connective circuitry;
performing a drilling process to form a plurality of first boreholes and second boreholes through the three-layered structure, wherein each first bore is disposed in a center of each hole, while each second bore is disposed in a center of each block;
forming a plurality of first plugs and second plugs to respectively fill up the first and second boreholes, while forming a plurality of first bulges and second bulges respectively on opening of the first and second boreholes on the first layer, wherein the first bulges on the first layer serve as working electrodes and the second bulges on the first layer serve as contact pads, wherein the first and second plugs connect the connective circuitry with the working electrodes and the contact pads;
removing the patterned first and second photoresist layers;
performing surface treatment to exposed surfaces of the three-layered structure;
forming a retaining wall around the reaction region and on the first layer;
attaching binding entities to the working electrodes; and
forming a cap layer to cover the first layer in the central reaction region, so that the central reaction region is sealed.
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28. A microelectronic system for detecting a bulge site, wherein the microelectronic system includes a reaction region, the system comprising:
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a plurality of micro-locations distributed in the reaction region, wherein each micro-location comprises;
a first electrode disposed in a center of the micro-location;
a second electrode surrounding the first electrode with a distance, thus enclosing a space, wherein the second electrode is electrically insulated from the first electrode without loaded fluid;
an attachment layer coupled to a surface of the first electrode;
a plurality of binding entities coupled the attachment layer, wherein the binding entities are immobilized onto the surface of the first electrode through the attachment layer; and
a permeation layer for supporting the binding entities , wherein the second electrodes isolate the first electrodes, acting as isolating walls, and wherein the space enclosed by the second electrode can hold loaded fluid;
a retaining wall around the reaction region;
a plurality of contact pads disposed outside the reaction region and surrounding the reaction region, for electrical operation;
a connective circuitry for connecting the first electrodes in the micro-locations and the contact pads;
an insulating layer for isolating the micro-locations and the connective circuitry, wherein the micro-locations are disposed on a first surface of the insulating layer and using the insulating layer as a base for the micro-locations, while a second surface of the insulating, opposite to the first surface, is attached to the connective circuitry;
a cap layer over the micro-locations for sealing the micro-locations in the reaction region;
a solution, including a plurality of test sample molecules, a redox-active mediator and an oxidant, added to the micro-locations in the sealed reaction region, wherein the test sample molecule can form a binding pair with the binding entity, thus forming a bulge site; and
a reference electrode applied to the micro-location for detecting the bulge site through the redox-active mediator.
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Specification