Implantable Power Sources and Sensors

• US 20080319287A1
• Filed: 07/13/2005
• Published: 12/25/2008
• Est. Priority Date: 07/14/2004
• Status: Active Grant

• Current Assignee: GluSense Ltd.
• Original Assignee: GluSense Ltd.
• Inventors: Gross, Yossi, Hyman, Tehila, Williger, Ben-Tsion, Neufeld, Tova
• Granted Patent: US 7,951,357 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61K 49/0045 the fluorescent agent being a peptide or protein used for imaging or diagnosis in vivo
• CPC Class Codes: A61K 49/0047 Green fluorescent protein [GFP]
• CPC Class Codes: A61K 49/0056 Peptides, proteins, polyamino acids
• CPC Class Codes: C07K 14/43595 from coelenteratae, e.g. medusae
• CPC Class Codes: C07K 2319/60 containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A protein is provided, including a glucose binding site, cyan fluorescent protein (CFP), and yellow fluorescent protein (YFP). The protein is configured such that binding of glucose to the glucose binding site causes a reduction in a distance between the CFP and the YFP. Substance monitoring apparatus (210) is also provided, including a semi-permeable barrier (212), adapted to be implanted in a body of a subject and to allow passage therethrough of a substance, while inhibiting passage therethrough of immune cells; and microorganisms (214), disposed within the semi-permeable barrier (212) so as to produce a measurable response to a level of the substance. A sensor (220) is adapted to measure the measurable response and not to measure a response of any mammalian cells that may be disposed within the semi-permeable barrier (212).

Claims

3. Apparatus for detecting a concentration of a substance in a subject, the apparatus comprising a housing adapted to be implanted in the subject, the housing comprising:

a fluorescence resonance energy transfer (FRET) measurement device; and

cells genetically engineered to produce, in situ, a FRET protein having a FRET complex comprising a fluorescent protein donor, a fluorescent protein acceptor, and a binding site for the substance.

1. The apparatus according to claim 3, wherein the protein that the cells are genetically engineered to produce comprises:

a glucose binding site;

cyan fluorescent protein (CFP); and

yellow fluorescent protein (YFP),

wherein the protein is configured such that binding of glucose to the glucose binding site a distance between the CFP and the YFP.

2. The apparatus of claim 1, wherein the protein is encoded by an isolated nucleic acid fragment having a nucleotide sequence represented by Sequence No. 1 (SEQ ID NO:

1).

18. The apparatus according to claim 3, comprising a promoter that is administrable to the subject and that regulates protein expression of the cells.

20. The apparatus according to claim 3, wherein the housing is configured to be implanted inside bone of the subject, and to detect a property of blood in fluid communication with the housing.

42. The apparatus according to claim 3, wherein the cells comprise slowly-dividing cells.

43. The apparatus according to claim 3, wherein the cells comprise beta cells.

44. The apparatus according to claim 3, wherein the cells comprise neuronal cells.

45. The apparatus according to claim 3, wherein the cells comprise liver cells.

46. The apparatus according to claim 3, wherein the substance includes glucose, and wherein the binding site comprises a binding site for glucose.

47. The apparatus according to claim 3, wherein the protein comprises a protein selected from the group consisting of:

blue fluorescent protein (BFP), green fluorescent protein (GFP), GFP/Rhodamine, FITC/Cy3, and FITC/Rhodamine.

48. The apparatus according to claim 3, wherein the protein comprises a leading peptide that is configured to direct the protein to cell membranes of the cells.

49. The apparatus according to claim 48, wherein the leading peptide is represented by Sequence No. 2 (SEQ ID NO:

2).

50. The apparatus according to claim 3, wherein the housing comprises a chamber which holds the cells.

51. The apparatus according to claim 3, wherein the cells are held directly within the housing, with no intervening chamber to hold the cells.

52. The apparatus according to claim 3, wherein the cells are disposed within a matrix.

53. The apparatus according to claim 3, wherein the cells are disposed in a suspension.

54. The apparatus according to claim 3, wherein the housing comprises a membrane that prevents passage therethrough of cells of the subject'"'"'s body while permitting passage therethrough of some molecules.

55. The apparatus according to claim 54, wherein the membrane is configured to prevent passage therethrough of the protein.

56. The apparatus according to claim 3, wherein the cells are configured such that the protein produced by the genetically-engineered cells becomes positioned on cell membranes of the cells.

57. The apparatus according to claim 3, comprising a drug capable of killing the cells, the drug being configured to be administered to the subject subsequently to the implantation of the housing in the subject.

4-17. -17. (canceled)

19. (canceled)

21-41. -41. (canceled)