Sample delivery system with laminar mixing for microvolume biosensing

• US 20040028559A1
• Filed: 05/05/2003
• Published: 02/12/2004
• Est. Priority Date: 11/06/2001
• Status: Abandoned Application

• Current Assignee: Peter Schuck
• Original Assignee: Peter Schuck
• Inventors: Schuck, Peter
• Application Number:
  US10/415,909
• Publication Number:
  US 20040028559A1
• Time in Patent Office: Days
• US Class Current: 422/68.1
• CPC Class Codes: B01F 2215/0431 Numerical size values, e.g. diameter of a hole or conduit, area, volume, length, width, or ratios thereof
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 31/651 Mixing by successively aspirating a part of the mixture in a conduit, e.g. a piston, and reinjecting it through the same conduit into the receptacle
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/712 for feeding fluids
• CPC Class Codes: B01F 35/717613 Piston pumps
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08

Abstract

A device and method for molecular or microanalytical sensing that includes a sample chamber containing a sensing device a first and second microchannel fluidly connected to the sample chamber and at least one pump for pumping a fluid sample back and forth from the first microchannel through the sample chamber to the second microchannel. At least one of the microchannels or the sample chamber has a width that causes molecular mixing of the sample by laminar flow as the sample is pumped back and forth. The microchannels may have a width of, for example, from about 10 mm to about 1 mm or from about 50 mm to about 500 mm. The sample chamber may have a volume of, for example, about 1 nl to about 10 ml or from about 10 nl to about 100 nl. The method is particularly useful for assessing the interaction between molecules in a solution with molecules immobilized on a surface or with the surface itself as in, for example, a biosensor.

Claims

1. A device for molecular sensing comprising:

a sample chamber;

a first microchannel in fluid communication with the sample chamber;

a second microchannel in fluid communication with the sample chamber; and

at least one pump to facilitate pumping of a fluid sample from the first microchannel through the sample chamber and into the second microchannel and from the second microchannel through the sample chamber and into the first microchannel;

wherein

at least one of the first microchannel, sample chamber and second microchannel having a width that causes molecular mixing of the sample by laminar flow within the fluid sample as the fluid sample moves through the at least one microchannel.

2. The device of claim 1, the microchannels having a width of from about 10 μ

m to about 1 mm.

3. The device of claim 1, the microchannels having a width of from about 50 μ

m to about 500 μ

m.

4. The device of claim 1, the sample chamber comprising a volume of about 1 nl to about 10 μ

l.

5. The device of claim 1, the sample chamber comprising a volume of from about 10 nl to about 100 nl.

6. The device of claim 1, the sample chamber comprising a microanalytical detector.

7. The device of claim 6, the microanalytical detector comprising a biosensor.

8. The device of claim 7, wherein the biosensor is a waveguide biosensor.

9. The device of claim 1, the pump comprising an oscillating pump.

10. The device of claim 9, the oscillating pump comprising a syringe pump.

11. The device of claim 1, further comprising a microanalytical detector capable of assessing binding rate of reactions between molecules selected from pairs of proteins, antibody and antigens, proteins and carbohydrates, proteins and peptides, proteins and nucleic acids, pairs of nucleic acids, and molecules and a surface.

12. The device of claim 1, further comprising a microanalytical detector capable of assessing equilibrium constants of reactions between molecules selected from pairs of proteins, antibody and antigens, proteins and carbohydrates, proteins and peptides, proteins and nucleic acids, pairs of nucleic acids, and molecules and a surface.

13. The device of claim 1, further comprising a microanalytical detector capable of assessing conformational changes of molecules.

14. The device of claim 13, wherein said molecules are biomolecules.

15. The device of claim 1, further comprising a microanalytical detector capable of assessing equilibrium constants of bimolecular reactions between a pair of interacting or chemically reacting molecules.

16. The device of claim 1, the device capable of assessing enzyme activity.

17. A method for microanalysis comprising:

pumping a fluid sample to be analyzed through a first microchannel and a sample chamber into a second microchannel, said sample chamber comprising a microanalytical detector,

reversing the flow of said fluid sample such that the fluid sample flows from the second microchannel into the sample chamber and then into the first microchannel, and wherein

the sample chamber is continuously filled with a portion of the fluid sample,

at least a portion of both the first microchannel and the second microchannel contains continuously a portion of the sample fluid, and

at least one of the first microchannel, sample chamber and second microchannel has a width that causes molecular mixing by laminar flow within the fluid sample as the fluid sample moves through the at least one microchannel.

18. The method of claim 17, the microanalytical detector comprising a biosensor.

19. The method of claim 18, the biosensor comprising a waveguide biosensor.

20. The method of claim 17, wherein the fluid sample has a volume of less than about 20 μ

l.

21. The method of claim 17, wherein the fluid sample has a volume of from about 3 μ

l to about 8 μ

l.

22. The method of claim 17, further comprising replacing the fluid sample with a buffer and monitoring a signal from the detector.

23. The method of claim 17, wherein the sample is analyzed to assess binding rates of reactions between molecules selected from the group consisting of pairs of proteins, antibody and antigens, proteins and carbohydrates, proteins and peptides, proteins and nucleic acids, pairs of nucleic acids, and molecules and a surface.

24. The method of claim 17, wherein the sample is analyzed to assess equilibrium constants of reactions between molecules selected from the group consisting of pairs of proteins, antibody and antigens, proteins and carbohydrates, proteins and peptides, proteins and nucleic acids, pairs of nucleic acids and molecules and a surface.

25. The method of claim 17, wherein the sample is analyzed to assess equilibrium constants of reactions between a pair of interacting or chemically reacting molecules.

26. The method of claim 17, wherein the sample is analyzed to assess enzyme activities.

27. The method of claim 17, wherein conformational changes in molecules are measured.

28. The method of claim 27, said molecules comprising biomolecules.

29. A device for microanalysis comprising:

a first microchannel fluidly coupled to a sample chamber that is in turn fluidly coupled to a second microchannel,

an oscillating pump to facilitate pumping of a fluid sample back and forth from the first microchannel to the sample chamber and into the second microchannel, and from the second microchannel to the sample chamber and into the first microchannel,

the sample chamber comprising a biosensor;

wherein

at least one of the first microchannel, sample chamber and second microchannel has a width that causes molecular mixing of the sample by laminar flow as the sample is pumped back and forth between the first microchannel, the sample chamber and the second microchannel.

30. A method for biosensing comprising:

providing a device according to claim 29;

aspirating a first air bubble into the device;

aspirating a sample comprising an analyte molecule into the device;

aspirating a second air bubble into the device;

activating the oscillating pump to cause the fluid sample to flow back and forth from the first microchannel to the sample chamber and into the second microchannel, and from the second microchannel to the sample chamber and into the first microchannel; and

detecting a signal from the biosensor, wherein

at least a portion of the fluid sample is in contact with the biosensor and at least a portion of the first and second microchannel contains at least a portion of the fluid sample.