Apparatus and methods for on-chip monitoring of cellular reactions

• US 7,560,267 B2
• Filed: 03/18/2002
• Issued: 07/14/2009
• Est. Priority Date: 03/18/2002
• Status: Active Grant

• Current Assignee: City University of Hong Kong
• Original Assignee: City University of Hong Kong
• Inventors: Yang, Mengsu, Yang, Jun, Li, Cheuk Wing
• Primary Examiner(s): LIU, SUE XU
• Application Number:
  US10/100,276
• Publication Number:
  US 20030175944A1
• Time in Patent Office: 2,675 Days
• Field of Search: 436/43, 436/52, 436/174, 436/180, 422/81, 422/100, 422/129, 422/68.1, 422/243, 209/105, 435/283.1, 435/308.1
• US Class Current: 435/283.1
• CPC Class Codes: B01F 25/3141 with additional mixing means other than injector mixers
• CPC Class Codes: B01F 25/4321 the subflows consisting of at least two flat layers which are recombined, e.g. using means having restriction or expansion zones
• CPC Class Codes: B01F 25/433 Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
• CPC Class Codes: B01F 25/4332 Mixers with a strong change of direction in the conduit for homogenizing the flow
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3039 with mixing achieved by diffusion between layers
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• 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: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: G01N 1/38 Diluting, dispersing or mixing samples

Abstract

This invention relates to apparatus and methods for on-chip monitoring of cellular reactions, and in particular to such an apparatus and method that enables soft-docking of cells by using a dam wall that is parallel to the direction of fluid flow. The invention further relates to an apparatus and method capable of generating a controlled concentration gradient, and in particular a concentration gradient such that the cells are aligned in the direction of the concentration gradient after docking.

Claims

1. An apparatus for on-chip monitoring of cellular reactions comprising:

a surface formed with a plurality of channels for fluid flow and a first inlet for supplying a cell bearing fluid to a first of said channels, wherein a second of said channels extends parallel and adjacent to said first channel for at least a part of their length defining a plurality of separate spaced-apart zones and wherein said first channel and said second channel are separated over said at least one part of their length by a wall defining a plurality of separate spaced-apart dams, said wall comprising a first height and said plurality of separate spaced-apart dams comprising a second height and wherein said second height is lower than said first height, a respective one of said plurality of separate spaced-apart dams being disposed in a respective one of said plurality of separate spaced-apart zones, over which said plurality of separate spaced-apart dams fluid flows from said first channel into said second channel, and wherein said wall disposed between adjacent ones of said plurality of separate spaced-apart dams is operable to inhibit the flow of fluid from said first channel to said second channel between said spaced-apart zones; and

a dilution channel for supplying a reagent, said dilution channel being bifurcated and intersecting with said first channel at two of said plurality of separate spaced-apart dams forming a first dilution intersection at the junction of said first channel and one of said bifurcated channels and a second dilution intersection at the junction of said first channel and another of said bifurcated channels for generating a concentration gradient of the reagent within said first channel whereby the reagent concentration varies in the direction of fluid flow in said first channel.

2. The apparatus as claimed in claim 1 wherein said first inlet for supplying a cell bearing fluid to said first channel is at a first liquid pressure, and wherein a second inlet is provided for supplying a fluid to said second channel at a second liquid pressure which is lower than the first liquid pressure.

3. The apparatus as claimed in claim 1 wherein said bifurcated dilution channels are perpendicular to said first channel at the intersection of said bifurcated dilution channels and said first channel.

4. The apparatus as claimed in claim 1 wherein said channels have a depth of about 18 microns.

5. The apparatus as claimed in claim 1 further comprising a cover disposed over said channels.