Measurement of concentrations and binding energetics

• US 20040038426A1
• Filed: 01/02/2003
• Published: 02/26/2004
• Est. Priority Date: 08/22/2002
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Manalis, Scott
• Granted Patent: US 7,387,889 B2
• Time in Patent Office: Days
• US Class Current: 436/514
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing

Abstract

Free-standing microfluidic channels are used to both transport and analyze molecules of interest. In a biochemical context, such molecules may be polypeptides, nucleic acids, or other biomolecules. The free-standing channels provide a real-time readout of concentration without the need for labeling with reporter molecules. The channels can also measure enthalpy values and equilibrium constants by detecting heat released from or absorbed by the sample.

Claims

1. A method of measuring at least one property relating to a chemical species of interest, the method comprising the steps of:

a. providing a microfluidic channel;

b. flowing the species through the channel to cause therein a chemical reaction between the species of interest and a second chemical species, the reaction being related to the at least one property and imparting a physical change to the channel; and

c. measuring the change to characterize the at least one property.

2. The method of claim 1 wherein the second chemical species is a capture moiety.

3. The method of claim 2 wherein the channel comprises an interior surface to which the capture moiety is bound.

4. The method of claim 2 wherein the capture moiety is contained in a gel within the channel.

5. The method of claim 2 wherein the capture moiety is not bound within the channel.

6. The method of claim 1 wherein the property is concentration of the species of interest.

7. The method of claim 1 wherein the property is binding energy between the species of interest and the second chemical species.

8. The method of claim 1 wherein the channel has a mechanical resonant frequency, the physical change imparted by the chemical reaction being alteration of the mechanical resonant frequency in relation to a mass of the species of interest.

9. The method of claim 7 wherein the physical change imparted by binding is bending of the channel.

10. The method of claim 9 wherein the channel comprises a thermal bimorph, the bending resulting from differential thermal expansion and indicating heat released by binding.

11. The method of claim 9 wherein the second chemical species is non-uniformly active within the channel, the bending resulting from differential surface stresses.

12. The method of claim 9 wherein the bending is detected optically.

13. Apparatus for measuring at least one property relating to a chemical species of interest, the apparatus comprising:

a. at least one microfluidic channel facilitating therein a chemical reaction between the species of interest and a second chemical species, the reaction being related to the at least one property and imparting a physical change to the channel; and

b. a detector for measuring the physical change to characterize the at least one property.

14. The apparatus of claim 13 wherein the second chemical species is a capture moiety.

15. The apparatus of claim 14 wherein the channel comprises an interior surface to which the capture moiety is bound.

16. The apparatus of claim 14 further comprising a gel within the channel, the gel containing the capture moiety.

17. The apparatus of claim 13 wherein the property is concentration of the species.

18. The apparatus of claim 13 wherein the property is binding energy.

19. The apparatus of claim 13 wherein the channel has a mechanical resonant frequency, the physical change imparted by the chemical reaction being alteration of the mechanical resonant frequency in relation to a mass of the species binding to the interior channel surface.

20. The apparatus of claim 18 wherein the physical change imparted by binding is bending of the channel.

21. The apparatus of claim 20 wherein the channel comprises a thermal bimorph, the bending resulting from differential thermal expansion and indicating heat released by binding.

22. The apparatus of claim 21 wherein the channel has a first coefficient of thermal expansion, the thermal bimorph including a layer in contact with the channel having a second coefficient of thermal expansion different from the first coefficient of thermal expansion.

23. The apparatus of claim 20 wherein the second chemical species is non-uniformly active within the channel, the bending resulting from differential surface stresses.

24. The apparatus of claim 13 comprising first and second channels each having a set of fingers, the sets of fingers interdigitating with each other and facilitating optical detection of a degree of bending of the first channel relative to the second channel.

25. A method of measuring separation among a plurality of chemical species of interest, the method comprising the steps of:

a. providing a microfluidic channel;

b. flowing the plurality of species through the channel under conditions causing the species to separate into fractions, the channel bending in response to a total mass therein; and

c. measuring the bending as the species flow through the channel to characterize the fractions.