SPATIAL IMAGING METHODS FOR BIOMEDICAL MONITORING AND SYSTEMS THEREOF

• US 20110319742A1
• Filed: 09/08/2010
• Published: 12/29/2011
• Est. Priority Date: 09/08/2009
• Status: Abandoned Application

• Current Assignee: Sensivida Medical Technologies, Inc.
• Original Assignee: Sensivida Medical Technologies, Inc.
• Inventors: Mir, Jose, Spoonhower, John, Agostinelli, John A., Demejo, Larry, Sarbadhikari, Kamal K.
• Application Number:
  US12/877,738
• Publication Number:
  US 20110319742A1
• Time in Patent Office: Days
• US Class Current: 600/407
• CPC Class Codes: A61B 2562/046 in a matrix array
• 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 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150175 Adjustment of penetration depth
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150419 comprising means for capillary action
• CPC Class Codes: A61B 5/150427 Specific tip design, e.g. for improved penetration characteristics
• CPC Class Codes: A61B 5/150435 Specific design of proximal end
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/150572 Pierceable protectors, e.g. shields, caps, sleeves or films, e.g. for hygienic purposes
• CPC Class Codes: A61B 5/150755 Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
• CPC Class Codes: A61B 5/15117 comprising biased elements, resilient elements or a spring, e.g. a helical spring, leaf spring, or elastic strap
• CPC Class Codes: A61B 5/15121 comprising piezos
• CPC Class Codes: A61B 5/15123 comprising magnets or solenoids
• CPC Class Codes: A61B 5/15151 Each piercing element being stocked in a separate isolated compartment
• CPC Class Codes: A61B 5/15163 Characterized by propelling the piercing element in an axial direction relative to the disc
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/685 : Microneedles
• CPC Class Codes: A61M 2037/0061 : Methods for using microneedles

Abstract

A method for monitoring at least one biomedical characteristic is disclosed. A first microneedle coated with one or more regions of a chemical sensing material is illuminated. One or more digital images are captured of the first microneedle, wherein at least one of the one or more digital images is captured after the first coated microneedle has been actuated to penetrate a subject'"'"'s skin. Pixel information is spatially extracted from the captured one or more images to define one or more pixel sample areas corresponding to the one or more regions of a chemical sensing material. One or more spectral characteristics are determined for each of the one or more pixel sample areas. The at least one biomedical characteristic is determined for each of the one or more pixel sample areas based on the determined one or more spectral characteristics for each of the one or more pixel sample areas.

Claims

1. A method for monitoring at least one biomedical characteristic, comprising:

illuminating a first microneedle coated with one or more regions of a chemical sensing material;

capturing one or more digital images of the first microneedle, wherein at least one of the one or more digital images is captured after the first coated microneedle has been actuated to penetrate a subject'"'"'s skin;

spatially extracting pixel information from the captured one or more images to define one or more pixel sample areas corresponding to the one or more regions of a chemical sensing material;

determining one or more spectral characteristics for each of the one or more pixel sample areas; and

determining the at least one biomedical characteristic for each of the one or more pixel sample areas based on the determined one or more spectral characteristics for each of the one or more pixel sample areas.

2. The method of claim 1, wherein the at least one of the one or more digital images captured after the first coated microneedle has been actuated to penetrate the subject'"'"'s skin is captured after the first coated microneedle has been extracted from the subject'"'"'s skin.

3. The method of claim 1, wherein the at least one of the one or more digital images captured after the first coated microneedle has been actuated to penetrate the subject'"'"'s skin is captured while the first coated microneedle is still penetrating the subject'"'"'s skin.

4. The method of claim 1, wherein at least another of the one or more digital images is captured before a reaction between at least one of the one or more regions of the chemical sensing material and at least one analyte.

5. The method of claim 4, wherein capturing the at least another of the one or more digital images before the reaction between the at least one of the one or more regions of the chemical sensing material and the at least one analyte comprises capturing the at least another of the one or more digital images before the first coated microneedle has been actuated to penetrate the subject'"'"'s skin.

6. The method of claim 4, wherein capturing the at least another of the one or more digital images before the reaction between the at least one of the one or more regions of the chemical sensing material and the at least one analyte comprises capturing the at least another of the one or more digital images after the first coated microneedle has been actuated to penetrate the subject'"'"'s skin.

7. The method of claim 4, wherein spatially extracting pixel information from the captured one or more images to define one or more pixel sample areas corresponding to the one or more regions of chemical sensing material comprises:

subtracting the at least another digital image from the at least one digital image of the captured one or more digital images to subtract a background.

8. The method of claim 1, wherein determining one or more spectral characteristics for each of the one or more pixel sample areas comprises determining a red pixel histogram, a green pixel histogram, and a blue pixel histogram.

9. The method of claim 4, wherein determining one or more spectral characteristics for each of the one or more pixel sample areas comprises:

determining an initial intensity from the at least another digital image for each of the one or more pixel sample areas corresponding to the one or more regions of the chemical sensing material;

determining a post-actuation intensity from the at least one digital image of the one or more digital images for each of the one or more pixel sample areas corresponding to the one or more regions of the chemical sensing material; and

determining a ratio of measured intensities as a ratio of the initial intensity to the post-actuation intensity for each of the one or more pixel sample areas corresponding to the one or more regions of the chemical sensing material.

10. The method of claim 9, wherein determining the at least one biomedical characteristic for each of the one or more pixel sample areas based on the determined one or more spectral characteristics for each of the one or more pixel sample areas comprises determining a log of the ratio of measured intensities for each of the one or more pixel sample areas corresponding to the one or more regions of the chemical sensing material.

11. The method of claim 10, wherein the log of the ratio of measured intensities for each of the one or more pixel sample areas is proportional to a concentration of one or more analytes targeted by corresponding one or more regions of the chemical sensing material.

12. The method of claim 1, wherein the at least one biomedical characteristic is a concentration of, a true/false indicator for a presence of, or a true/false indicator for a crossing of a threshold level for a target analyte selected from the group consisting of glucose, cholesterol, HDL cholesterol, LDL cholesterol, alcohol, estrogen-progesterone, cortisol, a physiological chemical, an ingested chemical, and an exposed chemical.

13. The method of claim 1, further comprising determining an insertion depth for the first microneedle based on the determined one or more spectral characteristics for each of the one or more pixel sample areas.

14. The method of claim 1, further comprising determining the at least one biomedical characteristic for each of the one or more pixel sample areas as a function of an insertion depth of the first microneedle based on a knowledge of an axial height for each of the one or more regions of the chemical sensing material coated on the first microneedle.

15. The method of claim 14, further comprising ignoring any of the at least one biomedical characteristics corresponding to an insertion depth which is not of interest.

16. The method of claim 1, wherein determining the at least one biomedical characteristic for each of the one or more pixel sample areas based on the one or more spectral characteristics for each of the one or more pixel sample areas comprises determining the at least one biomedical characteristic from one or more maxima of the one or more spectral characteristics for each of the one or more pixel sample areas.

17. The method of claim 1, further comprising:

illuminating a calibration microneedle coated with one or more calibration regions of the chemical sensing material;

capturing one or more digital calibration images of the calibration microneedle, wherein at least one of the one or more digital calibration images is captured after the calibration microneedle has been actuated to contact a reference analyte;

spatially extracting pixel information from the captured one or more calibration images to define one or more calibration pixel sample areas corresponding to the one or more calibration regions of the chemical sensing material;

determining one or more spectral calibration characteristics for each of the one or more calibration pixel sample areas; and

correcting the determination of the at least one biomedical characteristic for each of the one or more pixel sample areas based on the determined one or more spectral characteristics for each of the one or more pixel sample areas and the determined one or more spectral calibration characteristics.

18. The method of claim 1, further comprising updating an electronic medical record to include the determined at least one biomedical characteristic.

19. The method of claim 1, further comprising:

capturing at least one screening digital image of the first microneedle prior to a penetration of the subject'"'"'s skin with the first microneedle;

determining whether or not the first microneedle has been previously used from a comparison of one or more spectral characteristics for each of one or more spatially extracted pixel sample areas, corresponding to the one or more regions of the chemical sensing material in the captured at least one screening digital image, with an expected standard.

20. The method of claim 19, further comprising preventing the first microneedle from penetrating the subject'"'"'s skin if it is determined that the first microneedle has been previously used.

21. The method of claim 19, further comprising alerting the subject if it is determined that the first microneedle has been previously used.

22. A non-transitory computer readable medium having stored thereon instructions for monitoring at least one biomedical characteristic, comprising machine executable code which when executed by at least one machine, causes the machine to:

illuminate a first microneedle coated with one or more regions of a chemical sensing material;

capture one or more digital images of the first microneedle, wherein at least one of the one or more digital images is captured after the first coated microneedle has been actuated to penetrate a subject'"'"'s skin;

spatially extract pixel information from the captured one or more images to define one or more pixel sample areas corresponding to the one or more regions of a chemical sensing material;

determine one or more spectral characteristics for each of the one or more pixel sample areas; and

determine the at least one biomedical characteristic for each of the one or more pixel sample areas based on the determined one or more spectral characteristics for each of the one or more pixel sample areas.

23. The non-transitory computer readable medium of claim 22, wherein the at least one of the one or more digital images captured after the first coated microneedle has been actuated to penetrate the subject'"'"'s skin is captured after the first coated microneedle has been extracted from the subject'"'"'s skin.

24. The non-transitory computer readable medium of claim 22, wherein the at least one of the one or more digital images captured after the first coated microneedle has been actuated to penetrate the subject'"'"'s skin is captured while the first coated microneedle is still penetrating the subject'"'"'s skin.

25. The non-transitory computer readable medium of claim 22, wherein at least another of the one or more digital images is captured before a reaction between at least one of the one or more regions of the chemical sensing material and at least one analyte.

26. The non-transitory computer readable medium of claim 25, wherein capturing the at least another of the one or more digital images before the reaction between the at least one of the one or more regions of the chemical sensing material and the at least one analyte comprises capturing the at least another of the one or more digital images before the first coated microneedle has been actuated to penetrate the subject'"'"'s skin.

27. The non-transitory computer readable medium of claim 25, wherein capturing the at least another of the one or more digital images before the reaction between the at least one of the one or more regions of the chemical sensing material and the at least one analyte comprises capturing the at least another of the one or more digital images after the first coated microneedle has been actuated to penetrate the subject'"'"'s skin.

28. The non-transitory computer readable medium of claim 25, wherein the instructions to spatially extract pixel information from the captured one or more images to define one or more pixel sample areas corresponding to the one or more regions of chemical sensing material comprise instructions to subtract the at least another digital image from the at least one digital image of the captured one or more digital images to subtract a background.

29. The non-transitory computer readable medium of claim 22, wherein instructions to determine one or more spectral characteristics for each of the one or more pixel sample areas comprise instructions to determine a red pixel histogram, a green pixel histogram, and a blue pixel histogram.

30. The non-transitory computer readable medium of claim 25, wherein instructions to determine one or more spectral characteristics for each of the one or more pixel sample areas comprise instructions to:

determine an initial intensity from the at least another digital image for each of the one or more pixel sample areas corresponding to the one or more regions of the chemical sensing material;

determine a post-actuation intensity from the at least one digital image of the one or more digital images for each of the one or more pixel sample areas corresponding to the one or more regions of the chemical sensing material; and

determine a ratio of measured intensities as a ratio of the initial intensity to the post-actuation intensity for each of the one or more pixel sample areas corresponding to the one or more regions of the chemical sensing material.

31. The non-transitory computer readable medium of claim 30, wherein instructions to determine the at least one biomedical characteristic for each of the one or more pixel sample areas based on the determined one or more spectral characteristics for each of the one or more pixel sample areas comprise instructions to determine a log of the ratio of measured intensities for each of the one or more pixel sample areas corresponding to the one or more regions of the chemical sensing material.

32. The non-transitory computer readable medium of claim 31, wherein the log of the ratio of measured intensities for each of the one or more pixel sample areas is proportional to a concentration of one or more analytes targeted by corresponding one or more regions of the chemical sensing material.

33. The non-transitory computer readable medium of claim 22, wherein the at least one biomedical characteristic is selected from the group consisting of glucose, cholesterol, HDL cholesterol, LDL cholesterol, alcohol, estrogen-progesterone, cortisol, a physiological chemical, an ingested chemical, and an exposed chemical.

34. The non-transitory computer readable medium of claim 22, further comprising instructions causing the machine to determine an insertion depth for the first microneedle based on the determined one or more spectral characteristics for each of the one or more pixel sample areas.

35. The non-transitory computer readable medium of claim 22, further comprising instructions causing the machine to determine the at least one biomedical characteristic for each of the one or more pixel sample areas as a function of an insertion depth of the first microneedle based on a knowledge of an axial height for each of the one or more regions of the chemical sensing material coated on the first microneedle.

36. The non-transitory computer readable medium of claim 35, further comprising instructions causing the machine to ignore any of the at least one biomedical characteristics corresponding to an insertion depth which is not of interest.

37. The non-transitory computer readable medium of claim 22, wherein instructions to determine the at least one biomedical characteristic for each of the one or more pixel sample areas based on the one or more spectral characteristics for each of the one or more pixel sample areas comprise instructions to determine the at least one biomedical characteristic from one or more maxima of the one or more spectral characteristics for each of the one or more pixel sample areas.

38. The non-transitory computer readable medium of claim 22, further comprising instructions for causing the machine to:

illuminate a calibration microneedle coated with one or more calibration regions of the chemical sensing material;

capture one or more digital calibration images of the calibration microneedle, wherein at least one of the one or more digital calibration images is captured after the calibration microneedle has been actuated to contact a reference analyte;

spatially extract pixel information from the captured one or more calibration images to define one or more calibration pixel sample areas corresponding to the one or more calibration regions of the chemical sensing material;

determine one or more spectral calibration characteristics for each of the one or more calibration pixel sample areas; and

correct the determination of the at least one biomedical characteristic for each of the one or more pixel sample areas based on the determined one or more spectral characteristics for each of the one or more pixel sample areas and the determined one or more spectral calibration characteristics.

39. The non-transitory computer readable medium of claim 22, further comprising instructions for causing the machine to update an electronic medical record to include the determined at least one biomedical characteristic.

40. A biomedical monitor for determining at least one biomedical characteristic, comprising:

at least one microneedle coated with one or more regions of a chemical sensing material;

an actuator configured to move the at least one microneedle from a retracted position to an engaged position whereby at least a portion of the at least one microneedle enters a subject'"'"'s skin;

at least one light source configured to illuminate the at least one microneedle;

an image sensor configured to capture one or more digital images of the at least one microneedle;

a computing device coupled to the image sensor and configured to;

spatially extract pixel information from the captured one or more images to define one or more pixel sample areas corresponding to the one or more regions of a chemical sensing material;

determine one or more spectral characteristics for each of the one or more pixel sample areas; and

determine the at least one biomedical characteristic for each of the one or more pixel sample areas based on the determined one or more spectral characteristics for each of the one or more pixel sample areas.

41. The biomedical monitor of claim 40, wherein at least one of the one or more digital images is captured after the at least one microneedle has been moved to the engaged position.

42. The biomedical monitor of claim 40, wherein:

the one or more regions of the chemical sensing material comprise a plurality of regions of the chemical sensing material; and

at least two of the plurality of regions comprise a different chemical sensing material.

43. The biomedical monitor of claim 40, wherein the chemical sensing material comprises a medium which changes color when in contact with a target chemical specie.

44. The biomedical monitor of claim 40, wherein the chemical sensing material comprises a medium which fluoresces when in contact with a target chemical specie.

45. The biomedical monitor of claim 40, wherein the chemical sensing material comprises a medium which changes its fluorescence characteristics when in contact with a target chemical specie.

46. The biomedical monitor of claim 40, wherein the chemical sensing medium comprises a material selected from the group consisting of glucose oxidase, peroxidase, glucose dehydrogenase, hexokinase-glucokinase, rhenium bipyridine, boronic acid having fluorophores, NBD-fluorophores, europium teracycline, oxidizable color-change dyes such as 4-aminoantipyrine, chromotropic acid, and potassium iodide in the presence of a tri-iodide ion host such as amylose, starch, polyvinyl acetate, polyvinyl alcohol, polyvinyl pyrrolidone, nylon, cellulose, and chitosan.

47. The biomedical monitor of claim 40, wherein the at least one microneedle comprises a porous portion.

48. The biomedical monitor of claim 40, wherein the at least one microneedle comprises a capillary film.

49. The biomedical monitor of claim 40, wherein the at least one microneedle comprises at least one roughened surface.

50. The biomedical monitor of claim 40, wherein the at least one microneedle comprises a semi-permeable membrane overlay.

51. The biomedical monitor of claim 40, wherein the at least one microneedle comprises micro-particulate diffuse particles.

52. The biomedical monitor of claim 40 wherein the at least one microneedle comprises a semi-permeable membrane overlay comprising one or more of the chemical sensing material.

53. The biomedical monitor of claim 40, wherein the at least one microneedle is optically transmissive to one or more wavelengths of light being captured by the image sensor.

54. The biomedical monitor of claim 40, wherein the image sensor is selected from the group consisting of:

a CCD sensor, a multi-channel CCD sensor, a CMOS image sensor, a multi-channel CMOS image sensor, a multispectral imaging system, and a spectrometer.

55. The biomedical monitor of claim 40, wherein the image sensor is oriented substantially over the at least one microneedle in the engaged position.