Systems and methods for monitoring health and delivering drugs transdermally

• US 7,931,592 B2
• Filed: 03/28/2005
• Issued: 04/26/2011
• Est. Priority Date: 06/01/2000
• Status: Active Grant

• Current Assignee: Georgetown University, Leidos, Inc. (Leidos Holdings, Inc.)
• Original Assignee: Georgetown University, Science Applications International Corporation
• Inventors: Peck, Carl C., White, Robert C., Schneider, Thomas W., Paranjape, Makarand, Currie, John F.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US11/090,156
• Publication Number:
  US 20050182307A1
• Time in Patent Office: 2,220 Days
• Field of Search: 600/309, 600/310, 600/322, 600/323, 600/324, 600/316, 600/473, 600/476, 600/317
• US Class Current: 600/309
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/150007 Details
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

The present invention pertains to a system and method for transdermal sampling, comprising: at least one sampler for retrieving and transferring at least one analyte obtained transdermally from the skin of a subject; at least one detector system for identifying and quantifying said at least one analyte; and at least one logic module for (i) receiving and storing input data from said at least one detector, (ii) relating the input data to other data obtained from the subject, (iii) displaying output information, (iv) transmitting the output information to another system, and (v) controlling the operation of said at least one sampler and at least one detector.

Claims

1. A transdermal sampling system, comprising:

at least two samplers for transdermally retrieving and transferring at least one analyte from the skin of a subject, wherein each of the at least two samplers are included in a single microfabricated device comprising a microfluidic assembly;

each of the at least two samplers including at least one microheater configured for ablating a portion of the stratum corneum of the skin of a subject on demand to facilitate access to interstitial fluid from the subject'"'"'s underlying viable epidermis;

at least one detector system for identifying and quantifying said at least one analyte separately for each of the at least two samplers; and

at least one logic module for (i) receiving and storing input data from said at least one detector, (ii) relating the input data to other data obtained from the subject relating to the condition of the subject, (iii) displaying output information indicative of health and clinical state of the subject as determined from the relating of the input data to the other data, (iv) transmitting the output information to another system, and (v) controlling the operation of said at least one sampler and at least one detector.

2. The system of claim 1, wherein said at least one detector system comprises an optical detection system comprised of at least one light source effective to excite fluorophores, and at least one detector for detecting fluorescence from excited fluorophores.

3. The system of claim 2, wherein said light source comprises at least one LED or at least one laser.

4. The system of claim 1, further comprising means for holding the the microfabricated device in contact with the skin of the subject.

5. The transdermal sampling system according to claim 4, wherein the adhesive substantially prevents movement of the transdermal sampling system relative to the skin of the subject.

6. The transdermal sampling system according to claim 4, wherein the adhesive serves to prevent loss of a physiologically compatible fluid.

7. The transdermal sampling system according to claim 4, wherein the adhesive is water impermeable.

8. The system of claim 4, wherein the means for holding is an adhesive.

9. The system of claim 1, further comprising at least one substance located in each of said at least two samplers which is capable of binding an analyte of interest, and said substance being detectable by said at least one detector system.

10. The system of claim 1, further comprising means for monitoring predetermined physiological data as said other data, for relating to the input data by said at least one logic module.

11. The system of claim 1, further comprising means for monitoring environmental conditions data as said other data, for relating to the input data by said at least one logic module.

12. The system of claim 1, wherein said at least one detector system comprises a patch sensitive to at least one analyte for changing color in response to contact with said at least one analyte, and at least one detector for detecting a change in color of the patch.

13. The device of claim 1, wherein said at least one detector system comprises a colorimetric detection system comprised of a colorimetric analyte sensitive region, wherein a color change in the colorimetric analyte sensitive region by an observer indicates the presence of an analyte.

14. The transdermal sampling system according to claim 1, wherein the microfluidic assembly comprises at least one serpentine capillary channel.

15. The transdermal sampling system according to claim 1, wherein each of the at least two samplers further comprises:

at least one reservoir channel;

at least one bottom capping section; and

at least one top capping section.

16. The transdermal sampling system according to claim 15, wherein the at least one reservoir channel further comprises at least one seal for retaining a physiologically compatible fluid within the at least one reservoir channel.

17. The transdermal sampling system according to claim 16, wherein the at least bottom capping section includes the at least one microheater.

18. The transdermal sampling system according to claim 15, wherein the at least one top capping section comprises two or more electrodes.

19. The transdermal sampling system according to claim 18, wherein the two or more electrodes serve to assist the flow of a physiologically compatible fluid through an at least one serpentine capillary channel.

20. The transdermal sampling system according to claim 15, further comprising a sensor for detecting the at least one analyte.

21. The transdermal sampling system according to claim 20, wherein the sensor for detecting the at least one analyte comprises a patch sensitive to the at least one analyte for changing color in response to contact with the at least one analyte, and at least one detector for detecting a change in color of the patch.

22. The transdermal sampling system according to claim 1, wherein the microfluidic assembly contains a physiologically compatible fluid that transfers at least one analyte obtained transdermally from the skin of a subject.

23. The transdermal sampling system according to claim 1, wherein at least one surface of the microfluidic assembly is modified in a manner to enhance sampling function.

24. The transdermal sampling system according to claim 23, wherein the modification of the at least one surface of the microfluidic assembly prevents the adsorption of protein to the at least one surface of the microfluidic assembly.

25. The transdermal sampling system according to claim 23, wherein the modification of the at least one surface of the microfluidic assembly attaches to the at least one surface of the microfluidic assembly at least one specific-binding molecule which specifically binds the at least one analyte.

26. The system of claim 1, further comprising at least one substance located in each of said at least two samplers which is capable of reacting with an analyte of interest, and said substance being detectable by said at least one detector system.

27. A microfabricated device for allowing remote monitoring of a subject, comprising:

at least one sampler unit body for transdermally retrieving at least one analyte from interstitial fluid of a subject, wherein the sampler unit body is a microfabricated device including;

at least two samplers;

at least one microheater associated with each of the at least two samplers configured for ablating a portion of the stratum corneum of the skin of a subject on demand to facilitate access to interstitial fluid from the subject'"'"'s underlying viable epidermis

at least one detector system connected to said at least one sampler unit body for identifying and quantifying at least one analyte obtained from a subject separately for each of the at least two samplers; and

a transmitter/receiver for transmitting data relating to at least one analyte detected by said detection system to a logic module for processing thereby, and for allowing control of the microfabricated device by a logic module.

28. The device of claim 27, wherein said at least one detector system comprises a plurality of detector systems, each of said plurality of detector systems connected to a corresponding one of said at least two samplers.

29. The device of claim 27, wherein the sampler unit body is configured to substantially adhere to the skin of a subject.

30. The device of claim 27, further comprising at least one substance located in said sampler unit body which is capable of binding an analyte of interest, and said substance being detectable by said at least one detector system.

31. The device of claim 27, wherein said at least one detector system comprises a patch sensitive to at least one analyte for changing color in response to contact with said at least one analyte, positioned for contact with said at least one analyte, and at least one detector positioned for detecting a change in color of the patch.

32. The device of claim 27, wherein each of said at least two samplers includes a capillary channel extending therethrough for sampling analyte from the skin of a subject through said capillary channel;

and at least one detector chamber associated with said at least one detection system, and connected with said capillary channel for detecting analytes received within the detector chamber.

33. The device of claim 32, wherein each of said at least two samplers comprises at least one reservoir connected with said capillary channel, wherein a fluid retained in the at least one reservoir transfers from the reservoir to the subject'"'"'s skin into said capillary channel.

34. The device of claim 33, wherein said sampler unit body further comprises a microheater disposed to be in close proximity to a subject'"'"'s skin surface at a location proximate to where said fluid is pumped into contact with the skin of a subject, wherein the microheater ablates a portion of the stratum corneum of the skin of a subject.

35. The device of claim 32, wherein said sampler unit body is silicon.

36. The device of claim 27, wherein said at least one detector system comprises an optical detection system comprised of light sources effective to excite fluorophores, and at least one detector for detecting fluorescence from excited fluorophores.

37. The device of claim 36, wherein said light source comprises at least one LED or at least one laser.

38. The device of claim 27, further comprising at least one substance located in each of said at least two samplers which is capable of reacting with an analyte of interest, and said substance being detectable by said at least one detector system.

39. A microfabricated device for sampling analytes from the skin of a subject, comprising:

at least two samplers for transdermally retrieving and transferring at least one analyte from the skin of a subject, wherein each of the at least two samplers are included in a single microfabricated device;

each of the at least two samplers including at least one microheater configured for ablating a portion of the stratum corneum of the skin of a subject on demand to facilitate access to interstitial fluid from the subiect'"'"'s underlying viable epidermis;

a detection chamber for receiving analytes retrieved from the skin of a subject;

a photonic detection system, comprising a photonics source located attached to said microfabricated device in association with said detection chamber for separately detecting analytes for each of the at least two samplers.

40. The device of claim 39, wherein said photonics source is at least one LED or at least one laser.

41. The device of claim 39, further comprising substances in said device which bind with selected analytes, and which fluoresce when said photonics source applies radiation thereto.

42. A microfabricated device for sampling analytes from the skin of a subject, comprising:

at least two samplers for transdermally retrieving and transferring at least one analyte from the skin of a subject, wherein each of the at least two samplers are included in a single microfabricated device;

each of the at least two samplers including at least one microheater configured for ablating a portion of the stratum corneum of the skin of a subject on demand to facilitate access to interstitial fluid from the subject'"'"'s underlying viable epidermis;

a detection chamber for receiving analytes retrieved from the skin of a subject;

a patch which changes color when contacted by predetermined analytes, located attached to said microfabricated device in association with said detection chamber for separately detecting analytes for each of the at least two samplers.

43. A device for sampling and detecting analytes retrieved from the skin of a subject, comprising:

at least two microfluidic channels for retrieving and transferring at least one analyte from the skin of a subject to a detector, wherein said detector identifies and quantifies said at least one analyte separately for each of the at least two microfluidic channels; and

each of the at least two microfluidic channels including a microheater configured for ablating a portion of the stratum corneum of the skin of a subject on demand to facilitate access to interstitial fluid from the subject'"'"'s underlying viable epidermis which may contain the at least one analyte.

44. A method of biomedically monitoring a subject'"'"'s condition, the method comprising:

ablating a subject'"'"'s skin on demand via a first microheater to allow interstitial fluid to perfuse therethrough;

collecting interstitial fluid from the subject'"'"'s ablated skin at a first sampler associated with the first microheater;

ablating the subject'"'"'s skin on demand via a second microheater to allow interstitial fluid to perfuse therethrough;

collecting interstitial fluid from the subiect'"'"'s ablated skin at a second sampler associated with the second microheater;

wherein the first microheater, the first sampler, the second microheater and the second sampler are part of a single microfabricated device comprising a microfluidic assembly; and

identifying and quantifying at least one type of selected molecules contained in the collected interstitial fluid separately for each of the first and second samplers.

45. The method of claim 44, wherein the at least one type of molecule is a metabolic marker of stress.

46. The method of claim 44, wherein the at least one type of molecule is at least one of glucose, bilirubin, D-amino acids, an insecticide, atropine, pralidoxime, cytokine, dextromethorphan, caffeine, antihistamines, an organophosphate, microbial toxin, inflammatory sequeli to microbial toxin, spore metabolite, prealbumin, C-reactive protein, troponin I, estrogen, and testosterone.

47. The method of claim 44, further comprising monitoring at least one of the subject'"'"'s vital physiological statistics.

48. The method of claim 47, wherein said at least one of the subject'"'"'s vital physiological statistics comprises at least one of body temperature, pulse rate, blood pressure, and heart activity.

49. The method of claim 44, further comprising monitoring and detecting environmental conditions in which the subject is located.

50. The method of claim 44, wherein said identifying and quantifying comprises transferring said at least one type of molecule to a patch which changes color when in contact with said at least one type of molecule, and detecting a change in color of the patch.

51. The method of claim 44, wherein said identifying and quantifying comprises binding the at least one type of molecule with a second type of molecule which fluoresces when irradiated, irradiating the at least one type of molecule bound to the second type of molecule, and detecting any resultant fluorescence.

52. The method of claim 51, wherein the source for irradiating is a laser or an LED.

53. A microfabricated device for allowing remote monitoring of a subject, comprising:

at least one sampler unit body, wherein the sampler unit body is a microfabricated device comprising a microfluidic assembly, said microfluidic assembly including;

at least one reservoir containing a fluid and

at least one channel either directly or indirectly fluidly connected to the at least one reservoir arranged wherein the at least one channel receives the fluid from the at least one reservoir after the fluid retrieves the at least one analyte from the skin and transfers the at least one analyte through the at least one channel; and

at least one detector in association with the at least one channel to detect the at least one analyte transferred through the at least one channel.

54. The device of claim 53, wherein the reservoir retains the fluid in the reservoir with a breakable seal, wherein the breaking of the breakable seal releases the fluid.

55. The system of claim 53, wherein a pump pumps the fluid into contact with the skin of a subject.

56. The system of claim 55, further comprising a microheater disposed to be in close proximity to a subject'"'"'s skin surface at a location proximate to where said fluid is pumped into contact with the skin of a subject, wherein the microheater ablates a portion of the stratum corneum of the skin of a subject.

57. The system of claim 53 wherein the at least one channel is a capillary.

58. A transdermal sampling system, comprising:

at least two samplers for transdermally retrieving at least one analyte from the skin of a subject, wherein each of the at least two samplers are included in a single microfabricated device;

each of the at least two samplers including at least one microheater configured for ablating a portion of the stratum corneum of the skin of a subject on demand to facilitate access to interstitial fluid from the subject'"'"'s underlying viable epidermis;

at least one detector system for identifying and quantifying said at least one analyte separately for each of the at least two samplers; and

at least one logic module for (i) receiving and storing input data from said at least one detector, (ii) relating the input data to other data (iii) displaying output information as determined from the relating of the input data to the other data, (iv) transmitting the output information to another system, and (v) controlling the operation of said at least one sampler and at least one detector.

59. The system of claim 58, wherein said at least one detector system comprises an optical detection system comprised of at least one light source effective to excite fluorophores, and at least one detector for detecting fluorescence from excited fluorophores.

60. The system of claim 59, wherein said light source comprises at least one LED or at least one laser.

61. The system of claim 58, further comprising means for holding the microfabricated device in contact with the skin of the subject.

62. The system of claim 58, further comprising at least one substance located in each of said at least two samplers which is capable of binding an analyte of interest, and said substance being detectable by said at least one detector system.

63. The system of claim 58, further comprising means for monitoring predetermined physiological data as said other data, for relating to the input data by said at least one logic module.

64. The system of claim 58, further comprising means for monitoring environmental conditions data as said other data, for relating to the input data by said at least one logic module.

65. The system of claim 58, wherein said at least one detector system comprises a patch sensitive to at least one analyte for changing color in response to contact with said at least one analyte, and at least one detector for detecting a change in color of the patch.