Microchip and method for detecting molecules and molecular interactions

• US 9,863,941 B2
• Filed: 04/01/2005
• Issued: 01/09/2018
• Est. Priority Date: 04/01/2004
• Status: Active Grant

• Current Assignee: Nanyang Technological University
• Original Assignee: Nanyang Technological University
• Inventors: Li, Changming
• Primary Examiner(s): Shukla, Ram R
• Assistant Examiner(s): MARCSISIN, ELLEN JEAN
• Application Number:
  US11/547,405
• Publication Number:
  US 20080108095A1
• Time in Patent Office: 4,666 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/141 Preventing contamination, tampering
• 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 2300/0851 Bottom walls
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

A microchip with flow-through inlet (104) and outlet (106) channels and test channels (108). The test channels (108) are in fluid communication with the inlet (104) and outlet (106) channels, through inlets (114) and outlets (116) respectively. Each test channel (108) has one test site therein for detection of specific molecules or molecular interactions. The inlet (114) in a test channel (108) is elevated from the outlet (116) of the test channel (108) and the outlet (116) is elevated from a fluid level (124) in the outlet channel (106). Back diffusion from outlet channel (106) to the test channels (108) and from the test channels (108) to the inlet channel (104) can thus be inhibited to reduce or eliminate cross-interference between different test sites. The microchip can be useful as a flow-through high density enzyme immunoassay array device with high-throughput.

Claims

1. A microchip comprising:

a substrate;

an inlet channel in said substrate;

an outlet channel in said substrate for guiding fluid below a fluid level in said outlet channel;

a plurality of test channels in said substrate formed between said inlet channel and said outlet channel, for guiding fluid flow from said inlet channel to said outlet channel, each one of said test channels having an inlet connected with said inlet channel and an outlet connected with said outlet channel, said inlet elevated from said outlet for inhibiting back flow through said inlet, said outlet elevated from said fluid level for inhibiting back flow through said outlet; and

one test site in each one of said test channels, for detection of at least one specific molecule and a molecular interaction at said test site;

wherein each one of said inlet channel, said outlet channel, and said test channels has a substantially flat bottom, said bottom of said inlet channel elevated from said bottoms of said test channels, said bottoms of said test channels elevated from said bottom of said outlet channel and elevated from said fluid level in said outlet channel;

wherein at least one of said test channels comprises a well for holding fluid therein; and

wherein at least one of said test channels comprises an overflow wall for forming said well, said overflow wall defining the outlet of said at least one of said test channels.

2. The microchip of claim 1, wherein said inlet channel and said outlet channel are adapted to allow a liquid to flow at a greater rate in said outlet channel than in said inlet channel.

3. The microchip of claim 1, wherein each one of said test sites comprises a surface suitable for immobilizing specific molecules thereon.

4. The microchip of claim 1, further comprising probe molecules immobilized at each one of said test sites, said probe molecules having specific affinity to selected target molecules.

5. The microchip of claim 4, wherein different probe molecules are immobilized at different ones of said test sites for detecting different target molecules.

6. The microchip of claim 1, further comprising a plurality of electrodes, one of said electrodes at each one of said test sites.

7. The microchip of claim 6, wherein at least one of said test channels comprises a narrowed section proximate said test site in said at least one test channel for guiding fluid towards said test site.

8. The microchip of claim 6, wherein said plurality of electrodes are first electrodes, said microchip further comprising a plurality of second electrodes, one of said second electrodes in each one of said test channels.

9. The microchip of claim 8, wherein said first electrodes are interconnected and said second electrodes are interconnected, such that each pair of said electrodes in each one of said test channels is uniquely addressable.

10. The microchip of claim 8, further comprising probe molecules immobilized proximate said first electrodes.

11. The microchip of claim 1, wherein said test channels extend substantially in parallel.

12. The microchip of claim 1, further comprising a dilution channel formed in said substrate, said dilution channel in fluid communication with said inlet channel and having a first inlet for reception of a first fluid and at least one second inlet for reception of a second fluid to dilute said first fluid.

13. The microchip of claim 12, wherein said at least one second inlet comprises a plurality of second inlets.

14. The microchip of claim 1, wherein said substrate comprises polydimethylsiloxane (PDMS).

15. The microchip of claim 14, wherein a PDMS surface in each one of at least one of said test sites is coated with aminopropyltriethoxysilane (APTES), thus forming a PDMS-APTES surface.

16. The microchip of claim 15, wherein probe molecules are covalently immobilized on said PDMS-APTES surface through cross-linkers.

17. The microchip of claim 16, wherein said cross-linkers comprise at least one of glutaraldehyde and 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide.

18. The microchip of claim 1, wherein at least one of said inlet channel, said outlet channel and said test channels is adapted for connection to at least one of a pump and a valve for regulating fluid flow.

19. The microchip of claim 1, further comprising at least one fluid in said inlet channel, said outlet channel, and said test channels, wherein fluid level in each of said test channels does not exceed fluid level in said inlet channel.

20. The microchip of claim 19, wherein the fluid level in said outlet channel does not exceed the fluid level at the outlet of each of said test channels.