Devices and methods for biochip multiplexing

• US 7,172,897 B2
• Filed: 11/05/2001
• Issued: 02/06/2007
• Est. Priority Date: 01/11/2000
• Status: Expired due to Term

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Olsen, Gary T., Kayyem, Jon Faiz, O'Connor, Stephen D., Blackburn, Gary, Zenhausern, Frederic, Pietri, Robert, Grodzinski, Piotr, Duong, Hau H., Terbrueggen, Robert Henry
• Primary Examiner(s): REDDING, DAVID A
• Application Number:
  US09/993,342
• Publication Number:
  US 20060160205A1
• Time in Patent Office: 1,919 Days
• Field of Search: 422/58, 422/102, 435/286.5, 435/286.7, 435/287.2, 435/287.6, 435/288.5, 435/288.7, 204/403, 204/409, 204/545, 204/547, 204/643
• US Class Current: 435/287.2
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3033 using heat to mix or move the fluids
• CPC Class Codes: B01F 33/403 for mixing liquids B01F33/402, B01F33/405, B01F33/406 take precedence
• CPC Class Codes: B01L 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/024 Storing results with means integrated into the container
• 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 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1883 using thermal insulation
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0611 duck bill valves
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: B01L 2400/0661 : shape memory polymer valves
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 7/525 : with physical movement of samples between temperature zones
• CPC Class Codes: B82Y 15/00 : Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 : Manufacture or treatment of nanostructures
• CPC Class Codes: G01N 2001/021 : Correlating sampling sites with geographical information, e.g. GPS
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00326 : Analysers with modular structure
• CPC Class Codes: G01N 35/00871 : Communications between instruments or with remote terminals

Abstract

The invention is directed to devices that allow for simultaneous multiple biochip analysis. In particular, the devices are configured to hold multiple cartridges comprising biochips comprising arrays such as nucleic acid arrays, and allow for high throughput analysis of samples.

Claims

1. An apparatus for analysis of a plurality of biochips, each biochip comprising an array of electrodes comprising capture binding ligands and an auxiliary electrode, the apparatus comprising:

a) a plurality of sets of stations wherein each set comprises;

i) a plurality of stations, each configured to receive at least one of said plurality of biochips, wherein each station comprises a plurality of array interconnects for electrical communication with said array of electrodes of a first biochip of said plurality of biochips and at least one auxiliary interconnect positioned for electrical communication with an auxiliary electrode of said first biochip;

ii a thermocontroller, configured to independently thermally control one of said plurality of said sets;

b) a signal generator coupled to said plurality of array interconnects and said auxiliary interconnect and configured to apply an input signal to said electrodes of said array of electrodes of said first biochip during an electrochemical measurement; and

c) a detector coupled to said plurality of array interconnects and configured to receive an output signal from said electrodes of said array of electrodes of said first biochip during said electrochemical measurement.

2. An apparatus according to claim 1, wherein said signal generator comprises a potentiostat configured to regulate a voltage between said auxiliary electrode and said array of electrodes of said first biochip.

3. An apparatus according to claim 2, wherein said detector comprises a current detector configured to measure a current.

4. An apparatus according to claim 1, wherein said first biochip further comprises a reference electrode, and said station further includes a reference interconnect positioned for electrical communication with said reference electrode.

5. An apparatus according to claim 1, further comprising a multiplexor coupled to said detector and said plurality of array interconnects, the multiplexor configured to identify a selected interconnect from said plurality of array interconnects and couple said selected interconnect to the detector.

6. An apparatus according to claim 1 further comprising a digital filter coupled to said detector and configured to filter said output signal.

7. An apparatus according to claim 6 further comprising an analog to digital converter coupled to said detector and at least one of said electrodes, said analog to digital converter configured to digitize said output signal.

8. An apparatus according to claim 1, further comprising a first biochip inserted into a first station.

9. An apparatus according to claim 8, wherein said each electrode of said array of electrodes further comprises a self-assembled monolayer.

10. An apparatus according to claim 8, wherein at least one of said electrodes of said array of electrodes further comprises a hybridization complex comprising said capture binding ligand, a target, and a probe comprising an electron transfer moiety.

11. An apparatus according to claim 10, wherein said electron transfer moiety comprises ferrocene.

12. An apparatus according to claim 1 wherein said thermocontrollers comprises a temperature sensor and a temperature regulator.

13. An apparatus according to claim 12 wherein at least one of said temperature regulators comprise a Peltier thermal block.

14. An apparatus according to claim 1 further comprising a processor coupled to at least one of said thermocontrollers and configured to provide a control signal to said thermocontroller for thermal regulation of its respective set.

15. An apparatus for analysis of a plurality of biochips, each biochip comprising an array of electrodes comprising capture binding ligands and an auxiliary electrode, the apparatus comprising

a) a plurality of sets of stations wherein each set comprises:

i) a plurality of stations, each configured to receive at least one of said plurality of biochips, wherein each station comprises a plurality of array interconnects for electrical communication with said array of electrodes of a first biochip of said plurality of biochips and at least one auxiliary interconnect positioned for electrical communication with an auxiliary electrode of said first biochip;

b) a signal generator coupled to said plurality of array interconnects and said auxiliary interconnect and configured to apply an input signal to said electrodes of said array of electrodes of said first biochip during an electrochemical measurement; and

c) a detector coupled to said plurality of array interconnects and configured to receive an output signal from said electrodes of said array of electrodes of said first biochip during said electrochemical measurement.

16. An apparatus according to claim 15, further comprising an active electrode select multiplexor coupled to said plurality of array interconnects of each station.

17. An apparatus according to claim 15, further comprising a plurality of thermocontrollers, each configured to independently thermally control one of said plurality of sets.

18. An apparatus according to claim 16, further comprising an auxilliary electrode select multiplexor, said auxilliary electrode select multiplexor coupled to said signal generator and said plurality of auxilliary interconnects and configured to select at least one of said plurality of auxilliary interconnects as an active auxilliary interconnect and couple said active auxilliary interconnect to said signal generator.