Phase change sensor

• US 20050164299A1
• Filed: 05/28/2004
• Published: 07/28/2005
• Est. Priority Date: 06/03/2003
• Status: Active Grant

• Current Assignee: Cantimer, Inc.
• Original Assignee: Bay Materials, LLC (Straumann Holding AG)
• Inventors: Stewart, Ray F.
• Granted Patent: US 7,794,657 B2
• Time in Patent Office: Days
• US Class Current: 435/7.100
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A device is disclosed which is a highly sensitive and selective sensor. The device is comprised of a sensor material secured into a fixed position on substrate, a deformable arm and a signaling component which creates a detectable signal in response to movement of the arm. The sensitivity of the device is enhanced by using a sensor material which undergoes a dramatic change in volume which may be accompanied by a phase change in response contact with a target such a molecule of interest. The selectivity of the device is enhanced by incorporating highly specific binding receptors (e.g. antibodies) into the sensor material which receptors bind to specific targets (e.g. peptide epitopes). The binding of the target molecule to the receptor causes the sensor material to change dramatically in volume thereby moving the arm causing the signaling component (e.g. a piezoresistor) to create a detectable signal (e.g. change in resistance) thereby indicating the present of the target.

Claims

1. A sensor device, comprising:

a sensing material which undergoes a volumetric change of 0.5% or more when brought into contact with a target molecule;

a receptor which selectively binds the target molecule, the receptor being bound to the sensing material;

a deformable arm comprising a first end connected to a substrate and a second end positioned such that it is moved in response to the volumetric change of the sensing material; and

a signaling component which creates a detectable signal in response to deformation of the arm caused by movement of the second end of the arm.

2. The sensor device of claim 1, wherein the sensor material undergoes a volumetric change of 1% or more when brought into contact with the target material.

3. The sensor device of claim 1, wherein the sensor material undergoes a volumetric increase of 50% or more when brought into contact with the target material.

4. The sensor of claim 1, wherein the sensor material is a hydrogel, and is in a sheet having a thickness in a range of from about 5.0 microns to about 100 microns.

5. The sensor of claim 1, wherein the sensor material undergoes a phase transition when brought into contact with the target material.

6. The sensor of claim 1, wherein the sensing material is a hydrogel, the volumetric change is a decrease in volume and the phase transition is swelling transition.

7. The sensor device of claim 1, wherein the receptor is an antibody.

8. The sensor device of claim 7, wherein the antibody is a monoclonal antibody and the target molecule is an amino acid sequence.

9. The sensor device of claim 1 wherein the receptor is an amino acid sequence and the target molecule is an antibody.

10. The sensor device of claim 9, wherein the amino acid sequence is an epitope of a cell.

11. The sensor device of claim 10, wherein the cell is pathogenic bacteria.

12. The sensor device of claim 1, wherein the volumetric change is a decrease in volume, the receptor is a nucleotide sequence and the target molecule is a nucleotide sequence complementary to the receptor nucleotide sequence.

13. The sensor device of claim 12, wherein the receptor nucleotide sequence is chosen from a DNA sequence, a PNA and an RNA sequence having a degree of homology of 95% or more with the receptor sequence.

14. The sensor device of claim 1, wherein the receptor is an antibody and the target molecule is an amino acid sequence on a surface of a virus.

15. The sensor device of claim 1, wherein the signaling component is chosen from a piezoresistor, a piezoelectric component, and a capacitor.

16. The sensor device of claim 15, further comprising:

a source of voltage connected to the arm and applying an electrical potential difference between two points on the arm.

17. The sensor device of claim 16, further comprising:

a meter connected to the arm capable of measuring a change in resistance of the piezoresistor.

18. The sensor device of claim 1, wherein the second end of the arm is positioned with a space between the second end and a surface of the sensing material.

19. The sensor device of claim 18, wherein the space is 1 millimeter or less and further wherein the arm has a thickness ranging from 10 microns to 50 microns, a width ranging from 25 microns to 75 microns, and a length ranging from 100 microns to 200 microns.

20. The sensor device of claim 1, wherein the second end of the arm is connected to the sensing material.

21. The sensor device of claim 1, wherein the sensing material is a polymer.

22. The sensor device of claim 21, wherein the polymer is a hydrogel.

23. The sensor device of claim 1, wherein the sensing material is a crystalline material with a phase transition point between 10°

C. and 110°

C.

24. The sensor device of claim 23, wherein the phase transition point is chosen from a melting point and a glass transition point.

25. The sensor device of claim 1, wherein the second end of the arm is positioned inside the sensing material.

26. A sensing material, comprising:

a polymetric hydrogel comprising fibrous strands of polymer; and

a plurality of receptors disbursed throughout the hydrogel and bound to the strands.

27. The sensor device of claim 26, wherein the receptor is an antibody with a binding affinity of 10⁷ liters/mole or more relative to a target epitope.

28. The sensor device of claim 27, wherein the antibody is a monoclonal antibody and the target molecule is an amino acid sequence.

29. The sensor device of claim 26 wherein the receptor is an amino acid sequence and the target molecule is an antibody.

30. The sensor device of claim 29, wherein the amino acid sequence is an epitope of a cell.

31. The sensor device of claim 30, wherein the cell is pathogenic bacteria.

32. The sensor device of claim 26, wherein the receptor is a nucleotide sequence and the target molecule is a nucleotide sequence complementary to the receptor nucleotide sequence.

33. The sensor device of claim 32, wherein the receptor nucleotide sequence is chosen from a DNA sequence, a PNA sequence and an RNA sequence.

34. The sensor device of claim 26, wherein the receptor is an antibody and the target molecule is an amino acid sequence on a surface of a virus.

35. A method of detecting a target analyte, comprising the steps of:

monitoring a volume of a polymer comprised of hydrophobic groups and hydrophilic group while the polymer is in a controled aqueous environment absent the target analyte to determine a control volume;

comparing the control volume to a measured volume in a test aqueous environment where the analyte may be present; and

determining analyte presence in the test aqueous environment based on a change in volume of the polymer between the control aqueous environment and the test aqueous environment.

36. The method of claim 35, wherein the polymer comprises n-isopropyl hydrophobic groups and acrylamide hydrophilic groups.

37. The method of claim 35, wherein the control aqueous environment and the test aqueous environment are at the same temperature and pressure and further wherein the polymer volume is measured after being in the control and test aqueous environment for the same length of time.

38. A device for measuring an analyte comprising:

(a) a polymer having a first physical state in a control environmnet at temperature A and a second physical state in a control enviroinment at temperature B,

(b) a device for measuring a physical property of the polymer selected from one of volume, viscostity, modulus, heat capacity, conductivity or optical property,

(c) and a controlled heating element, capable of varying the temperature of the polymer from below temperature A to above temperature B while measuring one or more of the properties in the presence and absence of the analyte.

39. The device of claim 38 wherein the first and second physical states are chosen from glassy and rubbery.

41. The device of claim 38 whrerin the polymer is a hydogel.

42. The device of claim 38 wherein the analyte is selected from a hydrophobic organic molecule, a DNA or RNA fragment, a bacteria, virus, and an ion.

43. The device of claim 38 wherein the polymer is a crystalline material having a melting point or glass transition between 10°

C. and 110°

C.

44. The device of claim 38 wherein the polymer has attached to it an analyte specific moiety selected from one of DNA compliment, antibody, and an amine group.

45. The device of claim 43 wherin the polymer is prepared by template polymerization in the presence of the analyte.

46. The device of claim 38 wherein the temperature is varied at a rate of from about 1 degree C. per minute to about 10 degrees C. per minute.

47. The device in claim 38 wherein the polymer is a hydrogel having a LCST of from 1°

C. to 80°

C. and the analyte is an organic compound having a solubility in water of less than 1%.

40. The device of 38 wherein the first and second physical states are chosen from cyrstalline and amorphous.