MICROFLUIDIC DEVICES, METHODS AND SYSTEMS FOR DETECTING TARGET MOLECULES

• US 20090053732A1
• Filed: 07/16/2008
• Published: 02/26/2009
• Est. Priority Date: 07/16/2007
• Status: Abandoned Application

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Yen, Brian K.H., Vermesh, Ophir, Heath, James R.
• Application Number:
  US12/174,598
• Publication Number:
  US 20090053732A1
• Time in Patent Office: Days
• US Class Current: 435/7.100
• 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 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/0074 Biological products
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• 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 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: G01N 2458/10 Oligonucleotides as tagging agents for labelling antibodies
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: G01N 33/582 : with fluorescent label

Abstract

Microfluidic devices methods and systems for detecting a target in a fluidic component of a sample are shown. In such devices, methods and systems, the flow resistance of various channels where the sample is introduced is adjusted to control separation of the fluidic component from the sample and/or performance of assays for the detection of the target in the fluidic component in a controlled fashion. Such performance is controlled by binding affinity of the target with capture agents or diffusion of the target in the fluidic component.

Claims

1. A microfluidic device for detecting at least one target in a fluidic component of a fluid sample, the microfluidic device comprising:

an inlet for introducing the fluid sample in the microfluidic device,

a flowing channel in fluidic communication with the inlet, the flowing channel having a flowing channel resistance, and

an assaying channel in fluidic communication with the flowing channel, the assaying channel having an assaying channel resistance and carrying at least one capture agent or component thereof, the at least one capture agent or component thereof attached to the assaying channel, the at least one capture agent having a binding affinity for the target,

wherein

the flowing channel resistance and the assaying channel resistance are adapted to control flowing of the fluidic component from the flowing channel to the assaying channel, and

the assaying channel resistance is further adapted to allow binding of the target to the capture agent to form a detectable target capture agent binding complex, said binding controlled by at least one between said binding affinity and diffusion of said target in the fluidic component.

2. The microfluidic device of claim 1, wherein the flowing channel resistance and the assaying channel resistance are adapted to maximize flowing of the fluidic component from the flowing channel to the assaying channel.

3. The microfluidic device of claim 1, wherein the assaying channel comprises a first portion wherein the binding is controlled by said binding affinity and a second portion wherein the binding is controlled by said diffusion of said target molecule in the fluidic component.

4. The microfluidic device of claim 1, wherein the fluid is blood and the fluidic component is plasma.

5. The microfluidic device of claim 1, wherein the at least one capture agent or component thereof comprises

a substrate polynucleotide attached to the assaying channel.

6. The microfluidic device of claim 5, wherein the at least capture agent or component thereof further comprises

a polynucleotide-encoded protein comprising a protein and an encoding polynucleotide attached to the protein, wherein the protein specifically binds the at least one target and the encoding polynucleotide is specifically bound the substrate polynucleotide.

7. The microfluidic device of claim 1, wherein the at least one target comprises a plurality of targets and the at least one capture agent or component thereof comprises:

a plurality of substrate polynucleotides attached to the assaying channel, each polynucleotide of the plurality of substrate polynucleotides being sequence specific and positionally distinguishable from another.

8. The microfluidic device of claim 7, wherein the plurality of capture agents or component thereof further comprise

a plurality of polynucleotide-encoded proteins, each polynucleotide-encoded protein comprising a protein and an encoding polynucleotide attached to the protein, wherein the protein specifically binds to a predetermined target of the plurality of targets and the encoding polynucleotide specifically binds to a sequence-specific and positionally distinguishable polynucleotide of the plurality of polynucleotides attached to the assaying channel, each protein and encoding polynucleotide being bindingly distinguishable from another.

9. The microfluidic device of claim 1, wherein

the at least one capture agent or component thereof comprises a plurality of capture agents or component thereof,

each of the plurality of capture agents bindingly distinguishable and positionally distinguishable from another, each of the plurality of capture agents specifically binding the target molecule in a capture agent target binding complex, and

the plurality of capture agents are arranged on the assaying channel so that capture agent target binding complexes are detectable along substantially parallel lines forming a bar coded pattern.

10. A system for detecting at least one target in a fluidic component of a fluid sample, the system comprising

the microfluidic device of claim 5 and

a polynucleotide-encoded protein comprising a protein and an encoding polynucleotide attached to the protein, wherein the protein specifically binds a target and the encoding-polynucleotide specifically binds the substrate polynucleotide.

11. A system for detecting at least one target in a fluidic component of a fluid sample, the system comprising

the microfluidic device of claim 7 and

a plurality of polynucleotide-encoded proteins, each polynucleotide-encoded protein comprising a protein and an encoding polynucleotide attached to the protein, wherein the protein specifically binds to a predetermined target of the plurality of targets and the encoding polynucleotide specifically binds to a sequence-specific and positionally distinguishable polynucleotide of the plurality of polynucleotides attached to the assaying channel, each protein and encoding polynucleotide being bindingly distinguishable from another.

12. A method for detecting at least one target molecule in a fluidic component of a fluid sample, the method comprising:

providing the fluid sample in a flowing microfluidic channel;

controlling selective flowing of the fluidic component from the flowing microfluidic channel to an assaying microfluidic channel, the assaying microfluidic channel carrying at least one capture agent or a component thereof, the at least one capture agent attached to the assaying channel, the at least one capture agent having a binding affinity for the target molecule;

contacting the at least one target molecule with the at least one capture agent in the assaying microfluidic channel for a time and under conditions to allow binding of the at least one target molecule to the at least one capture agent to form a detectable target capture agent binding complex, said binding controlled by said binding affinity or by diffusion of said target molecule in the fluidic component; and

detecting the detectable target capture agent binding complex.

13. A microfluidic device for detecting at least one target in a fluidic component of a fluid sample, the microfluidic device comprising:

an inlet for introducing the fluid sample in the microfluidic device,

a flowing channel in fluidic communication with the inlet, the flowing channel having a flowing channel resistance, and

an assaying channel in fluidic communication with the flowing channel, the assaying channel having an assaying channel resistance,

wherein

the flowing channel resistance and the assaying channel resistance are configured to control flowing of the fluidic component from the flowing channel to the assaying channel, and

the assaying channel resistance is further configured to allow attachment of a target on a surface of said assaying channel, the attached target being detectable through labeled molecules specifically binding said target.