Devices for molecular biological analysis and diagnostics including waveguides
First Claim
1. An electronic device for performing active biological operations, comprising:
- an optically confining region including;
a support substrate having a first surface and a second surface and a via between the first and second surfaces;
a second substrate disposed in facing arrangement with the second surface of the support substrate;
a top member disposed in facing arrangement with the first surface of the support substrate, at least a portion of the top member forming an optically accessible window;
wherein the optically confining region is bounded by the via of the support substrate, the second substrate, and the top member;
a source of illumination;
an edge illumination layer having an input adapted to receive illumination from the source of illumination and a terminal edge that outputs the illumination, the edge illumination layer being disposed adjacent to the support substrate, the illumination from the terminal edge of the illumination layer being directed substantially parallel to the support substrate and into the optically confining region;
an array of microlocations disposed on the second substrate in the optically confining region.
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Accused Products
Abstract
Methods of manufacture and devices for performing active biological operations utilize various structures to advantageously collect and provide charged biological materials to an array of microlocations. In one embodiment, a device includes focusing electrodes to aid in the direction and transport of materials from a collection electrode to an array. Preferably, one or more intermediate transportation electrodes are utilized, most preferably of monotonically decreasing size between the collection electrode and the array, so as to reduce current density mismatches. In another aspect, a flow cell is utilized over devices to provide containment of solution containing materials to be analyzed. Preferably, the volume of the flow cell is more advantageously interrogated through use of relatively large collection and return electrodes, such as where the area of those electrodes relative to the footprint of the flowcell is at least 40%. In yet another embodiment, a first collection electrode is disposed adjacent an array, with a second collection electrode disposed on the at least an opposite portion of the array. Preferably, the combined area of the collection electrodes is a substantial fraction, preferably at least 50% of the area of the footprint of the flow cell. In yet another embodiment, a concentric ring design is provided. Various flip-chip embodiments are disclosed. A preferred embodiment utilizes a relatively small number of components, for example, five components, for a flip-chip device. A first substrate includes a via, through which solution flows to the underlying analytical chip, which a sealant between the chip and the first substrate. An overlying flow cell contains the solution. Novel manufacturing techniques are provided for utilizing the via as a shadow mask to constrain the flow of the sealant. A multiple site array system includes a row select and column select, which are preferably memory, and most preferably shift register memory. An improved current output circuit is of the current mirror type and serves to output selected current based upon input from the column select and row select.
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Citations
21 Claims
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1. An electronic device for performing active biological operations, comprising:
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an optically confining region including;
a support substrate having a first surface and a second surface and a via between the first and second surfaces;
a second substrate disposed in facing arrangement with the second surface of the support substrate;
a top member disposed in facing arrangement with the first surface of the support substrate, at least a portion of the top member forming an optically accessible window;
wherein the optically confining region is bounded by the via of the support substrate, the second substrate, and the top member;
a source of illumination;
an edge illumination layer having an input adapted to receive illumination from the source of illumination and a terminal edge that outputs the illumination, the edge illumination layer being disposed adjacent to the support substrate, the illumination from the terminal edge of the illumination layer being directed substantially parallel to the support substrate and into the optically confining region;
an array of microlocations disposed on the second substrate in the optically confining region. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. An electronic device for performing active biological operations, comprising:
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an optically confining region including;
a support substrate having a first surface and a second surface and a via between the first and second surfaces;
a second substrate disposed in facing arrangement with the second surface of the support substrate;
a top member disposed in facing arrangement with the first surface of the support substrate, at least a portion of the top member forming an optically accessible window;
wherein the optically confining region is bounded by the via of the support substrate, t he second substrate, and the top member;
a source of illumination;
a waveguide having an input adapted to receive illumination from the source of illumination and terminal edge that outputs the illumination, the waveguide being disposed adjacent to the support substrate, the illumination from the terminal edge of the waveguide being directed substantially parallel to the support substrate and into the optically confining region;
an array of microlocations disposed on the second substrate in the optically confining region. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20)
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21. A method of performing an assay on a sample containing charged biological material comprising the steps of:
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providing an optically confining region bounded by a substrate, a chip containing an array of microlocations, and an optically accessible top member;
introducing the sample into the optically confining region and hybridizing at least a portion of the charged biological material onto the microlocations of the array contained within the optically confining region;
illuminating the optically confining region with a waveguide, the waveguide having an input adapted to receive illumination from a source of illumination and an output which is disposed toward the array, the illumination from the output of the waveguide being directed substantially parallel to the substrate and chip; and
optically accessing the array.
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Specification