MICROFLUIDIC BASED INTEGRATED SAMPLE ANALYSIS SYSTEM

• US 20170001196A1
• Filed: 01/13/2014
• Published: 01/05/2017
• Est. Priority Date: 01/11/2013
• Status: Active Grant

• Current Assignee: Biomed Canada Corporation
• Original Assignee: Getwell Health Technology (Shenzhen) Co., Ltd.
• Inventors: Zhang, Gong, Ring, Marshall, Lin, Francis, Richmond, Edward Stewart
• Granted Patent: US 10,906,043 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• 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 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• 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 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: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6482 Sample cells, cuvettes
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 : Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 2201/0627 : Use of several LED's for spectral resolution
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing

Abstract

A portable microfluidic system capable of rapid diagnosis is described, which is able to analyze genetic, protein and cell composition of a sample in parallel for specific diseases from a relatively small sample. The method uses a single microfluidic chip integrated into a unique portable microfluidic platform and provides improved diagnostic accuracy, allows for frequent monitoring and is suitable for easy use in clinical settings.

Claims

1. A sample analysis system comprising:

a microfluidic chip comprising;

a sample input for applying a sample to the chip;

a separator connected to the sample input by a separation channel;

one or more reaction channels, each reaction channel being connected to the separator and being of varying length,

each said reaction channel being further connected to a respective outlet; and

a reagent inlet;

a thermoelectric semiconductor arranged to heat or cool one or more of said channels;

an LED array arranged to emit radiation at a specific wavelength to the microfluidic chip;

a detector arranged to detect fluorescence from said microfluidic chip; and

a control unit arranged to control the valves and analyze results from the detector.

2. The system according to claim 1 wherein flow of the sample through the microfluidic chip is regulated by differential pressure.

3. The system according to claim 2 wherein the differential pressure is generated by the respective channels being of different lengths, at least one of the channels including a valve for regulating flow along said one of the channels.

4. The system according to claim 1 wherein the separator is a gravity trap for separating blood into cells and plasma.

5. The system according to claim 1 including a cell reaction channel.

6. The system according to claim 1 including a PCR reaction chamber.

7. The system according to claim 1 including a protein detection channel.

8. A microfluidic chip which comprises:

a sample input for applying a sample to the microfluidic chip;

a separator connected to the sample input by a separator channel, said separator separating a sample into cells and fluid;

a cell analysis channel receiving the cells from the separator; and

at least one analysis channel receiving the fluid from the separator.

9. The microfluidic chip according to claim 8 wherein the analysis channel is selected from the group consisting of a DNA analysis channel, an RNA analysis channel, a protein analysis chamber, an antibody detection channel and combinations thereof.

10. A microfluidic chip which comprises:

at least three layers;

a top layer, a middle layer and a bottom layer;

a sample input for applying a sample to the microfluidic chip, said sample input being at the top layer of the microfluidic chip;

a separator connected to the sample input by a separator channel, said separator separating a sample into cells and fluid, said separator channel being at the top layer of the microfluidic chip and said separator being at the middle layer of the microfluidic chip;

a cell analysis channel being at the bottom layer of the microfluidic chip and receiving the cells from the separator; and

at least one analysis channel receiving the fluid from the separator.

11. The microfluidic chip according to claim 10 wherein the analysis channel may be selected from the group consisting of a DNA analysis channel, an RNA analysis channel, a protein analysis channel, an antibody detection channel and combinations thereof.

12. A method of analyzing a sample comprising:

providing a vacuum-sealed microfluidic chip which comprises;

a sample input for applying a sample to the microfluidic chip;

a separator connected to the sample input by a separator channel, said separator separating a sample into cells and fluid;

a cell analysis channel receiving the cells from the separator; and

at least one analysis channel receiving the fluid from the separator. and

at least one reagent input;

applying a sample comprising cells and fluid to the sample input;

releasing the vacuum seal of the of the microfluidic chip such that the sample flows into the separator channel;

separating the sample via the separator into cells and fluid;

passing the cells to a cell analysis channel;

separating the fluid into one or more analysis channels, said analysis channel being selected from the group consisting of a DNA analysis channel, an RNA analysis channel, an antibody detection channel, a protein analysis channel and combinations thereof;

incubating the respective channels at suitable temperatures for a suitable period of time with a thermoelectric semiconductor to drive reactions to completion;

emitting radiation over at least one suitable wavelength to the microfluidic chip viaan LED array;

detecting florescence from the microfluidic chip with a detector; and

analyzing results from the detector.

13. A method of analyzing a sample comprising:

providing a vacuum-sealed microfluidic chip which comprises;

at least three layers;

a top layer, a middle layer and a bottom layer,

a sample input for applying a sample to the microfluidic chip, said sample input being at the top layer of the microfluidic chip;

a separator connected to the sample input by a separator channel, said separator separating a sample into cells and fluid, said separator channel being at the top layer of the microfluidic chip and said separator being at the middle layer of the microfluidic chip;

a cell analysis channel being at the bottom layer of the microfluidic chip and receiving the cells from the separator;

at least one analysis channel receiving the fluid from the separator; and

at least one reagent input;

applying a sample comprising cells and fluid to the sample input;

releasing the vacuum seal of the of the microfluidic chip such that the sample flows into the separator channel;

separating the sample via the separator into cells and fluid;

passing the cells to a cell analysis channel;

separating the fluid into one or more analysis channels, said analysis channel being selected from the group consisting of a DNA analysis channel, an RNA analysis channel, an antibody detection channel, a protein analysis channel and combinations thereof;

incubating the respective channels at suitable temperatures for a suitable period of time with a thermoelectric semiconductor to drive reactions to completion;

emitting radiation over at least one suitable wavelength to the microfluidic chip viaan LED array;

detecting florescence from the microfluidic chip with a detector; and

analyzing results from the detector.