SYSTEMS AND METHODS FOR HIGH SPEED ARRAY PRINTING AND HYBRIDIZATION

• US 20130150266A1
• Filed: 02/01/2013
• Published: 06/13/2013
• Est. Priority Date: 01/19/2007
• Status: Active Grant

• Current Assignee: BioDot, Inc. (ATS Corp.)
• Original Assignee: BioDot, Inc. (ATS Corp.)
• Inventors: Eickhoff, Holger, Tisone, Thomas C.
• Granted Patent: US 8,920,752 B2
• Time in Patent Office: Days
• US Class Current: 506/37
• 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 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00385 Printing
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00698 Measurement and control of process parameters
• 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: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/065 sliding valves
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: C12M 41/00 Means for regulation, monitoring, measurement or control, e.g. flow regulation controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 : with sample on test slide
• CPC Class Codes: Y10T 436/119163 : with aspirator of claimed structure
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Novel and improved systems and methods for high speed arraying, hybridization, quantitative development and/or assaying are provided. Some embodiments provide a web based arraying format. Some other embodiments provide a sheet based arraying format. Some embodiments use a drop on drop assaying or hybridization mode. In some embodiments, a substantially inert substrate is utilized. In some other embodiments, an interactive substrate is utilized.

Claims

1. A high speed assaying system, comprising:

an array substrate comprising at least about forty target spots formed thereon in an array arrangement with center to center spacings of the order of about 1 mm between adjacent spots;

a dispense module comprising a dispense head, the dispense head comprising a plurality of non-contact dispensers arranged in a predetermined configuration with a predetermined spacing for dispensing reagent drops onto the array substrate with target spots formed thereon or therein such that the drops are precisely delivered at the position of the selected target spots to execute an assay or reaction;

a controller to monitor and control the dispensers and relative motion between the dispensers and the array substrate;

wherein when the system is in use the drops comprise a part of the system; and

wherein the system is configured to produce at least about ten million assayed substrates per year.

2. The high speed assaying system of claim 1, wherein the dispensers comprise solenoid actuated dispensers.

3. The high speed assaying system of claim 1, wherein the array substrate comprises an inert or passive substrate.

4. The high speed assaying system of claim 1, wherein the array substrate comprises an interactive or active substrate.

5. The high speed assaying system of claim 1, wherein the array substrate comprises a membrane.

6. The high speed assaying system of claim 1, wherein the array substrate comprises a film and a carrier arranged in a web format.

7. The high speed assaying system of claim 1, wherein the array substrate comprises a sheet format.

8. The high speed assaying system of claim 1, wherein the system further comprises at least one tandem motion system to achieve high throughput and substantially continuous operation.

9. The high speed assaying system of claim 1, wherein the drops are dispensed at a predetermined velocity and/or momentum to provide enhanced mixing and/or reaction kinetics with the selected array spot.

10. The high speed assaying system of claim 1, wherein the array substrate comprises a membrane, and wherein the system further comprises a membrane handling system.

11. The high speed assaying system of claim 1, wherein the system further comprises a sample storage machine to store sample plates, and wherein each of the sample plates comprises at least one array substrate.

12. The high speed assaying system of claim 11, wherein the sample plates comprise identifiers.

13. The high speed assaying system of claim 12, wherein the identifiers comprise barcode identifiers.

14. The high speed assaying system of claim 12, wherein the identifiers comprise punch card identifiers.

15. The high speed assaying system of claim 12, wherein the identifiers comprise Radio Frequency Identification Device (RFID) identifiers.

16. The high speed assaying system of claim 1, wherein the assaying comprises hybridization, and wherein the reagent drops and the target spots are selected such that when the drops and spots interact the hybridization is executed.

17. The high speed assaying system of claim 1, wherein the assaying comprises PCR assaying and the substrate comprises a PCR plate.

18. The high speed assaying system of claim 17, wherein the spots comprise at least one oligonucleotide.

19. The high speed assaying system of claim 18, wherein the oligonucleotide comprises a TaqMan®

probe.

20. The high speed assaying system of claim 17, wherein the reagent drops are dispensed through a layer of oil covering the spots.

21. The high speed assaying system of claim 1, wherein the reagent drops comprise a sample of one or more preselected reagents.

22. The high speed assaying system of claim 20, wherein the system further comprises a thermal cycling module to process the PCR plate.

23. The high speed assaying system of claim 22, wherein the system further comprises a read module downstream of the thermal cycling module.

24. The high speed assaying system of claim 1, wherein the dispensers comprise piezo dispensers.

25. The high speed assaying system of claim 1, wherein the array substrate comprises a glass slide.

26. The high speed assaying system of claim 1, wherein the reagent drops comprise a master mix.

27. The high speed assaying system of claim 1 in combination with a high speed array manufacturing system to form a combination comprising a high speed array manufacturing system and the high speed assaying system.

28. The combination of claim 27, wherein the high speed array manufacturing system is configured to produce at least about one million array substrates per year.

29. The combination of claim 27, wherein the controller is configured to use dispensing data from a text file in cooperation with a software program which is interfaced to the controller to precisely control and coordinate dispensing of the reagent drops, and wherein the text file is a user-defined text file created from a spreadsheet of values or template with lists of numbers of user-defined dispense volumes of one or more reagents and corresponding coordinates of the dispense locations.

30. The combination of claim 27, wherein the combination further comprises a tandem fluid source system which comprises two reagent sources correspondingly coupled to each dispenser, and wherein the tandem fluid source system is configured to sequentially fill and dispense reagent from each dispenser so that high throughput and substantially continuous operation of each of the dispensers is achieved.