Self-addressable self-assembling microelectronic systems and devices for molecular biological analysis and diagnostics

• US 7,947,486 B2
• Filed: 02/05/2007
• Issued: 05/24/2011
• Est. Priority Date: 07/07/1994
• Status: Expired due to Fees

• Current Assignee: Gamida for Life B.V.
• Original Assignee: Gamida for Life B.V.
• Inventors: Evans, Glen A., Heller, Michael J., Sosnowski, Ronald G., Tu, Eugene
• Primary Examiner(s): DeJong; Eric S
• Application Number:
  US11/702,353
• Publication Number:
  US 20100173792A1
• Time in Patent Office: 1,569 Days
• Field of Search: None
• US Class Current: 435/283.1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00686 Automatic
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00713 : Electrochemical synthesis
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: B01J 2219/00822 : Metal
• CPC Class Codes: B01J 2219/00828 : Silicon wafers or plates
• CPC Class Codes: B01J 2219/00844 : Comprising porous material
• CPC Class Codes: B01J 2219/00853 : Employing electrode arrangements
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 : Electrodes
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 : Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• CPC Class Codes: B01L 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 10/00 : Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 1/04 : on carriers C07K1/003, C07K1/006 take precedence
• CPC Class Codes: C07K 1/045 : using devices to improve synthesis, e.g. reactors, special vessels
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C12Q 1/6813 : Hybridisation assays
• CPC Class Codes: C12Q 1/6816 : characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/515 : characterised by the interaction between or sequential use of two or more arrays
• CPC Class Codes: C12Q 2565/607 : being a sensor, e.g. electrode
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G11C 13/0014 : comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 : comprising bio-molecules
• CPC Class Codes: G11C 19/00 : Digital stores in which the information is moved stepwise, e.g. shift registers
• CPC Class Codes: H01L 2224/45144 : Gold (Au) as principal constituent
• CPC Class Codes: H01L 2224/95144 : Magnetic alignment, i.e. using permanent magnetic parts in the semiconductor or solid-state body
• CPC Class Codes: H01L 2224/95145 : Electrostatic alignment, i.e. polarity alignment with Coulomb charges
• CPC Class Codes: H01L 2224/95147 : by molecular lock-key, e.g. by DNA
• CPC Class Codes: H01L 25/50 : Multistep manufacturing processes of assemblies consisting of devices, each device being of a type provided for in group H01L27/00 or H01L29/00 H01L21/50 takes precedence
• CPC Class Codes: H01L 29/6656 : using multiple spacer layers, e.g. multiple sidewall spacers
• CPC Class Codes: H01L 29/6659 : with both lightly doped source and drain extensions and source and drain self-aligned to the sides of the gate, e.g. lightly doped drain [LDD] MOSFET, double diffused drain [DDD] MOSFET
• CPC Class Codes: H01L 29/66628 : recessing the gate by forming single crystalline semiconductor material at the source or drain location
• CPC Class Codes: H01L 29/7834 : with a non-planar structure, e.g. the gate or the source or the drain being non-planar
• CPC Class Codes: H01L 2924/00 : Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• CPC Class Codes: H01L 2924/01019 : Potassium [K]
• CPC Class Codes: H01L 2924/0102 : Calcium [Ca]
• CPC Class Codes: H01L 2924/01046 : Palladium [Pd]
• CPC Class Codes: H01L 2924/01078 : Platinum [Pt]
• CPC Class Codes: H01L 2924/01079 : Gold [Au]
• CPC Class Codes: H01L 2924/10253 : Silicon [Si]
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus
• CPC Class Codes: Y10S 435/814 : Enzyme separation or purification
• CPC Class Codes: Y10S 436/805 : Optical property
• CPC Class Codes: Y10T 436/25125 : Digestion or removing interfering materials

Abstract

A method for analyzing nucleic acid obtained from a cell sample on a platform is described. A platform having a cell selector, a nucleic acid selector, and an array of microlocations, wherein at least one microlocation has an associated capture sequence, is provided. The cell selector is contacted with a cell sample, wherein a portion of the cells remain associated with the cell selector. At least a portion of cells associated with the cell selector are lysed to release a nucleic acid sample. The nucleic acid selector is then contacted with the nucleic acid sample, such that a portion of the nucleic acid sample remains associated with the nucleic acid selector. The associated nucleic acid sample is then released from the nucleic acid selector and then is contacted with the array of microlocations, such that at least a portion of the released nucleic acid sample hybridizes with the capture sequence.

Claims

1. A method for analyzing nucleic acid obtained from a cell sample on a platform, comprising the steps of:

providing a platform comprising a cell selector, a nucleic acid selector, and an array of microlocations, wherein at least one microlocation has an associated capture sequence;

contacting the cell selector with a sample containing cells, wherein at least a portion of the cells remain associated with the cell selector;

lysing the at least a portion of cells associated with the cell selector to release a nucleic acid sample;

contacting the nucleic acid selector with the nucleic acid sample, wherein at least a portion of the nucleic acid sample remains associated with the nucleic acid selector;

releasing the associated nucleic acid sample from the nucleic acid selector;

contacting the array of microlocations with the released nucleic acid sample, wherein at least a portion of the released nucleic acid sample hybridizes with the capture sequence.

2. The method of claim 1, wherein at least a portion of the cells remain associated with the cell selector through an affinity interaction.

3. The method of claim 1, wherein the platform further comprises a waste unit.

4. The method of claim 3, further comprising the step of transporting the portion of the sample that does not remain associated with the cell selector to the waste unit.

5. The method of claim 3, further comprising the step of transporting the portion of the nucleic acid sample that does not remain associated with the nucleic acid selector to the waste unit.

6. The method of claim 3, further comprising the step of transporting the portion of the released nucleic acid sample that does not remain associated with the array of microlocations to the waste unit.

7. The method of claim 1, wherein the at least a portion of cells associated with the cell selector are lysed using a reagent selected from the group consisting of detergents, chaotropic agents, lytic enzymes, proteinases, and combinations thereof.

8. The method of claim 1, wherein the at least a portion of cells associated with the cell selector are lysed using a proteinase selected from the group consisting of lysozyme, proteinase K, and pepsin.

9. The method of claim 7, further comprising the step of transporting the reagent to the cell selector using free field electrophoresis.

10. The method of claim 1, further comprising the step of reacting the at least a portion of the nucleic acid sample that remains associated with the nucleic acid selector with a restriction enzyme.

11. The method of claim 1, wherein the nucleic acid selector includes a first and second nucleic acid selector.

12. The method of claim 11, wherein the first nucleic acid selector is a crude DNA selector.

13. The method of claim 11, wherein the second nucleic acid selector is a restriction fragment selector.

14. The method of claim 1, wherein the cell sample is a blood sample.

15. The method of claim 1, wherein the cell sample is a urine sample.

16. The method of claim 1, wherein the nucleic acid sample comprises DNA.

17. The method of claim 1, further comprising at least one step of electronically transporting the nucleic acid sample to a target location on said platform before contacting said nucleic acid sample with said target location.

18. The method of claim 17, wherein said nucleic acid sample is transported by biasing said target location positive.

19. The method of claim 17, wherein said target location is the nucleic acid selector.

20. The method of claim 17, wherein said nucleic acid sample is the released nucleic acid sample and said target location is the at least one microlocation of the array of microlocations.