Implantable vascular system biosensor with grown capillary beds and uses thereof

• US 9,011,330 B2
• Filed: 07/09/2013
• Issued: 04/21/2015
• Est. Priority Date: 07/09/2012
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Sadek, Akram Sarwat, Scherer, Axel, Mujeeb-U-Rahman, Muhammad
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US13/938,156
• Publication Number:
  US 20140012122A1
• Time in Patent Office: 651 Days
• Field of Search: 600/309, 600/310, 600/344, 600/345, 600/347, 600/348
• US Class Current: 600/309
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/14 Coupling media or elements to improve sensor contact with skin or tissue
• CPC Class Codes: A61B 2562/164 the sensor is mounted in or on a conformable substrate or carrier
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/6846 specially adapted to be brought in contact with an internal body part, i.e. invasive
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: A61B 5/6876 Blood vessel

Abstract

An implantable biocompatible biosensor is described herein. The biosensor includes a chip layer including a plurality of holes fabricated vertically there through, a power source, one or more sensors on the chip layer and coupled to the power source and a hydrogel matrix including one or more angiogenesis stimulating factors in contact with the chip layer. The stimulating factors stimulate growth of organic material through the plurality of holes when the biosensor is implanted in a subject.

Claims

1. An implantable biocompatible biosensor comprising:

a chip layer including a plurality of holes fabricated vertically there through;

a power source;

one or more sensors on the chip layer and coupled to the power source; and

a hydrogel matrix including one or more angiogenesis stimulating factors in contact with the chip layer, the stimulating factors causing growth of organic material through the plurality of holes when the biosensor is implanted in a subject.

2. The biosensor of claim 1, wherein the one or more sensors include a photo diode and a laser diode configured for emitting light through the grown organic material to the photo diode.

3. The biosensor of claim 1, wherein each of the holes are 20-50 μ

m in diameter.

4. The biosensor of claim 3, wherein the spacing between each of the holes is the same as the diameter of the holes.

5. The biosensor of claim 1, further comprising:

a second chip layer including a second plurality of holes fabricated vertically through the second chip layer, the second chip layer located over the chip layer, the second plurality of holes in alignment with the plurality of holes; and

one or more sensors on the second chip layer and coupled to the power source; and

wherein the hydrogel matrix extends between the chip layer and the second chip layer.

6. The biosensor of claim 5, wherein the hydrogel matrix fills the first and second plurality of holes.

8. The biosensor of claims 1 or 7, further comprising a transmitter in communication with the one or more sensors, the one or more sensors each emitting a signal representative of a sensed characteristic of the grown organic material, the transmitter converting the signals from the one or more sensors into a digital signal representative of a sensed characteristic.

9. The biosensor of claims 1, wherein the power source is a photovoltaic cell.

10. The biosensor of claims 1 or 7, wherein the hydrogel matrix is bovine serum albumin-based, agarose-based, PEG-based, polyethylene oxide (PEO)-based, polyvinyl alcohol (PVA)-based, polyacrylic acid (PAA)-based, poly propylene furmarate-co-ethylene glycol (P(PF-co-EG))-based, alginate-based, chitosan-based, collagen-based, fibrin-based, gelatin-based, hyaluronic acid (HA)-based, poly 2-hydroxyethyl methacrylate (PHEMA)-based, poly carboxybetaine methacrylate (PCBMA)-based or a combination thereof.

11. The biosensor of claims 1 or 7, wherein the one or more sensors are any one or more of an electrode, nanoelectromechanical sensors, optical resonators, micro/nanoscale field effect transistor or a combination thereof.

12. The biosensor of claims 1 or 7, wherein the one or more angiogenesis stimulating factors induce formation of arterioles and capillaries when implanted into the subject.

13. The biosensor of claim 12, wherein the arterioles and capillaries form through the matrix in the holes in the chip.

14. The biosensor of claim 13, wherein the matrix absorbs analytes that diffuse through the arterioles and capillaries and the one or more sensors are configured to detect the analytes absorbed in the matrix.

15. The biosensor of claim 14, wherein the analytes are any one or more of proteins, ions, metabolites, gases or a combination thereof present in the blood.

16. The biosensor of claim 14, wherein the matrix further comprises agents that react with the analytes absorbed from the arterioles and capillaries into the matrix.

17. The biosensor of claims 1 or 7, wherein the angiogenesis stimulating factors is any one or more of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-1, FGF-2, platelet derived growth factor (PDGF), transforming growth factor (TGF)-β

, angiopoietins, matrix metalloproteinase (MMP) or a variant, mutant or peptidomimetic thereof, or a combination thereof.

24. The biosensor of claim 1 or 7, wherein the biosensor is configured to be implanted in the earlobe, areolar layer of the skin or within the dermis layer of the nail bed.

7. An implantable biocompatible biosensor comprising:

a first chip layer having a vertical hole between a top surface and a bottom surface;

a power source;

one or more sensors fabricated on the top surface;

a channel fabricated perpendicular to the vertical hole on the bottom surface; and

a hydrogel matrix having one or more angiogenesis stimulating factors filling the hole and the channel, the hydrogel matrix stimulating growth of organic material when the biosensor is implanted in a subject.

18. The biosensor of claim 7, further comprising a second chip layer having a hole in alignment with the hole of the first chip layer, wherein the second chip layer includes a laser diode and a photo-detector, the second chip layer located under the first chip layer and the hydrogel matrix filing the space between the first and second chip layers.

19. The biosensor of claims 2 or 18, wherein the laser diode is any one or more of double heterostructure lasers, quantum well lasers, quantum cascade lasers, separate confinement heterostructure lasers, distributed feedback lasers, vertical cavity surface emitting lasers (VCSELs), vertical external cavity surface emitting lasers (VECSELs) or external-cavity diode lasers.

20. The biosensor of claim 7, further comprising a transmitter in communication with the one or more sensors, the one or more sensors each emitting a signal representative of a sensed characteristic of the grown organic material, the transmitter converting the signals from the one or more sensors into a digital signal representative of a sensed characteristic.

21. The biosensor of claim 7, further comprising a microspectrometer for on-chip analysis of the analyte.

22. The biosensor of claim 7, wherein the matrix absorbs analytes that diffuse through the arterioles and capillaries and the one or more sensors are configured to detect the analytes absorbed in the matrix.

23. The biosensor of claim 7, wherein the matrix further comprises agents that react with the analytes from the arterioles and capillaries into the matrix.