Continuous monitoring of glucose and other living body constituents

• US 9,146,230 B2
• Filed: 06/20/2012
• Issued: 09/29/2015
• Est. Priority Date: 06/20/2011
• Status: Active Grant

• Current Assignee: Carmel Stemsense Limited
• Original Assignee: Carmel Stemsense Limited
• Inventors: Palti, Yoram
• Primary Examiner(s): Winakur, Eric
• Application Number:
  US13/527,708
• Publication Number:
  US 20120323094A1
• Time in Patent Office: 1,196 Days
• US Class Current: 1/1
• 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 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: G01N 33/5073 Stem cells
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

Methods and apparatuses for monitoring the level of glucose or other constituents in live subjects are disclosed. Stem cells are obtained from the subject and processed into cells that change their optical characteristics in response to a level of the constituent. The responsive cells are formed into clusters and implanted into in the subject'"'"'s body at locations that permit optical monitoring from outside the subject'"'"'s body. The implanted cell clusters are illuminated and the reflected illumination from each of the cell clusters is detected. Changes in the optical characteristics of the cell clusters that correspond to the responses of the cell clusters are identified, and the identified changes are mapped to a constituent level based on calibration data for each cell cluster. An indication of the constituent level in the subject is then output.

Claims

1. A method of monitoring a glucose level in a live subject, comprising the steps of:

obtaining at least one stem cell from the subject;

processing the at least one stem cell into a plurality of signal-generating cells that change their optical characteristics in response to changes in glucose concentration;

forming the plurality of signal-generating cells into at least two cell clusters;

determining, prior to implantation, for each of the at least two cell clusters, calibration data that relates responses of the respective cell cluster to glucose levels;

implanting the at least two cell clusters into in the subject'"'"'s body at locations that permit optical characteristics of the at least two cell clusters to be detected from outside the subject'"'"'s body after implantation;

illuminating the at least two implanted cell clusters;

detecting reflected illumination from each of the at least two cell clusters;

identifying changes in the optical characteristics of the cell clusters that correspond to the responses of the cell clusters, for each of the at least two cell clusters, based on changes in the amount of reflected illumination detected in the detecting step;

mapping, for each of the at least two cell clusters, the identified change in optical characteristics to a glucose level based on the calibration data for the respective cell cluster; and

outputting an indication of the glucose level in the subject based the glucose levels obtained in the mapping step.

2. The method of claim 1 wherein the obtaining step comprises obtaining at least one stem cell from a hair follicle of the subject.

3. The method of claim 1 wherein, in the processing step, the at least one stem cell is processed to yield a plurality of signal-generating cells with additional connexons in the cell membrane to promote synchronization.

4. The method of claim 1 wherein, in the forming step, the plurality of signal-generating cells are formed into cell clusters that are between 100 and 200 microns in diameter by collecting signal-generating cells into clumps.

5. The method of claim 1 wherein, in the determining step, calibration data that relate responses of the respective cell clusters to glucose levels are determined simultaneously for all the cell clusters by capturing a video of all the cell clusters and analyzing the video.

6. The method of claim 1 wherein, in the implanting step, a dye is implanted together with the cell clusters, wherein the dye is selected to make the locations of the cell cluster more visible.

7. The method of claim 1 further comprising the step of selecting the at least two cell clusters from a larger set of cell clusters by

capturing a video of the larger set of cell clusters responding to changes in glucose levels,

analyzing the video to determine which cell clusters in the larger set work well, and

selecting cell clusters that work well for implantation in the subject.

8. The method of claim 1 further comprising the steps of:

positioning an array of sensors elements in a vicinity of the cell clusters;

monitoring the illumination reflected from the sensor elements;

identifying, based on the monitored illumination, which sensor element in the array provides a strong return for each of the at least two cell clusters;

storing an indication of which sensor elements were identified in the identifying step; and

using the stored indication to select which sensor elements should be used for subsequent determinations of glucose levels.

9. An apparatus for monitoring a glucose level in a live subject into which at least two cell clusters have been implanted at locations that permit optical characteristics of the at least two cell clusters to be detected from outside the subject'"'"'s body after implantation, the apparatus comprising:

a light source that is oriented to shine illumination onto the at least two implanted cell clusters when the apparatus is fastened in place in a vicinity of the at least two implanted cell clusters;

a memory that holds calibration data for the at least two implanted cell clusters that relates responses of each cell cluster to glucose levels, wherein the calibration data is obtained prior to implantation of the cell clusters;

an array of light sensors that are oriented to receive illumination reflected from the at least two implanted cell clusters when the apparatus is fastened in place, and generate intensity data; and

a processor that is programmed to perform the steps of (a) inputting the intensity data, (b) identifying activity in the cell clusters, for each of the at least two implanted cell clusters, based on changes the intensity data, (c) mapping, for each of the at least two implanted cell clusters, the identified activity to a glucose level based on the calibration data stored in the memory, and (d) outputting an indication of the glucose level in the subject based a result of the mapping.

10. The apparatus of claim 9, further comprising a fastener that is configured to hold the apparatus in place on the subject'"'"'s body in the vicinity of the at least two implanted cell clusters.

11. The apparatus of claim 9, wherein the processor is further programmed to perform the steps of (e) identifying, based on the inputted intensity data, which elements in the array of light sensors provides a strong return for each of the at least two implanted cell clusters, and (f) using the identified elements to make subsequent determinations of glucose levels.

12. A method of monitoring a constituent level in a live subject, comprising the steps of:

obtaining at least one stem cell from the subject;

processing the at least one stem cell into a plurality of cells that change their optical characteristics in response to a level of the constituent;

forming the plurality of responsive cells into at least two cell clusters;

determining, prior to implantation, for each of the at least two cell clusters, calibration data that relates responses of the respective cell cluster to constituent levels;

implanting the at least two cell clusters into in the subject'"'"'s body at locations that permit optical characteristics of the at least two cell clusters to be detected from outside the subject'"'"'s body after implantation;

illuminating the at least two implanted cell clusters;

detecting reflected illumination from each of the at least two cell clusters;

identifying changes in the optical characteristics of the cell clusters that correspond to the responses of the cell clusters, for each of the at least two cell clusters, based on changes in the amount of reflected illumination detected in the detecting step;

mapping, for each of the at least two cell clusters, the identified change in optical characteristics to a constituent level based on the calibration data for the respective cell cluster; and

outputting an indication of the constituent level in the subject based the constituent levels obtained in the mapping step.

13. The method of claim 12 wherein the obtaining step comprises obtaining at least one stem cell from a hair follicle of the subject.

14. The method of claim 12 wherein, in the processing step, the at least one stem cell is processed to yield a plurality of cells with additional connexons in the cell membrane to promote synchronization.

15. The method of claim 12 wherein, in the determining step, calibration data that relate responses of the respective cell clusters to constituent levels are determined simultaneously for all the cell clusters by capturing a video of all the cell clusters and analyzing the video.

16. The method of claim 12 wherein, in the implanting step, a dye is implanted together with the cell clusters, wherein the dye is selected to make the locations of the cell cluster more visible.

17. The method of claim 12 further comprising the step of selecting the at least two cell clusters from a larger set of cell clusters by

capturing a video of the larger set of cell clusters responding to changes in constituent levels,

analyzing the video to determine which cell clusters in the larger set work well, and

selecting cell clusters that work well for implantation in the subject.

18. The method of claim 12 further comprising the steps of:

positioning an array of sensors elements in a vicinity of the cell clusters;

monitoring the illumination reflected from the sensor elements;

identifying, based on the monitored illumination, which sensor element in the array provides a strong return for each of the at least two cell clusters;

storing an indication of which sensor elements were identified in the identifying step; and

using the stored indication to select which sensor elements should be used for subsequent determinations of constituent levels.

19. An apparatus for monitoring a constituent level in a live subject into which at least two cell clusters have been implanted at locations that permit optical characteristics of the at least two cell clusters to be detected from outside the subject'"'"'s body after implantation, the apparatus comprising:

a light source that is oriented to shine illumination onto the at least two implanted cell clusters when the apparatus is fastened in place in a vicinity of the at least two implanted cell clusters;

a memory that holds calibration data for the at least two implanted cell clusters that relates responses of each cell cluster to constituent levels, wherein the calibration data is obtained prior to implantation of the cell clusters;

an array of light sensors that are oriented to receive illumination reflected from the at least two implanted cell clusters when the apparatus is fastened in place, and generate intensity data; and

a processor that is programmed to perform the steps of (a) inputting the intensity data, (b) identifying activity in the cell clusters, for each of the at least two implanted cell clusters, based on changes the intensity data, (c) mapping, for each of the at least two implanted cell clusters, the identified activity to a constituent level based on the calibration data stored in the memory, and (d) outputting an indication of the constituent level in the subject based a result of the mapping.

20. The apparatus of claim 19, further comprising a fastener that is configured to hold the apparatus in place on the subject'"'"'s body in the vicinity of the at least two implanted cell clusters.

21. The apparatus of claim 19, wherein the processor is further programmed to perform the steps of (e) identifying, based on the inputted intensity data, which elements in the array of light sensors provides a strong return for each of the at least two implanted cell clusters, and (f) using the identified elements to make subsequent determinations of constituent levels.