US 12,268,512 B2
Method and apparatus for the capture of intra-cellular activity
Bruce T Hope, Ellicott City, MD (US); Mark A Wells, San Diego, CA (US); and Gregory D Sutton, Del Mar, CA (US)
Assigned to Galiana Technology, Inc., San Diego, CA (US); and National Institutes of Health, Office of Technology Transfer, Rockville, MD (US)
Filed by Galiana Technology Inc., San Diego, CA (US); and National Institutes of Health, Office of Technology Transfer, Rockville, MD (US)
Filed on Apr. 18, 2023, as Appl. No. 18/135,738.
Application 18/135,738 is a continuation of application No. 16/450,895, filed on Jun. 24, 2019, granted, now 11,627,907.
Application 16/450,895 is a continuation of application No. 14/834,334, filed on Aug. 24, 2015, abandoned.
Claims priority of provisional application 62/041,028, filed on Aug. 23, 2014.
Prior Publication US 2023/0404465 A1, Dec. 21, 2023
Int. Cl. A61B 5/00 (2006.01); A61B 5/07 (2006.01); A61B 5/145 (2006.01); A61B 5/1473 (2006.01)
CPC A61B 5/4064 (2013.01) [A61B 5/0031 (2013.01); A61B 5/076 (2013.01); A61B 5/14546 (2013.01); A61B 5/1473 (2013.01); A61B 5/6868 (2013.01); A61B 2560/0204 (2013.01); A61B 2562/028 (2013.01); A61B 2562/0285 (2013.01); Y10S 977/774 (2013.01)] 15 Claims
OG exemplary drawing
 
1. A method for monitoring intracellular activity, comprising:
providing a first intracellular monitoring device that includes a first semiconductor substrate, wherein the first intracellular monitoring device is located completely inside a first cell, and a longest dimension, of the first semiconductor substrate, is no more than one micrometer,
the first intracellular monitoring device including:
a first P-type layer, manufactured on the first semiconductor substrate,
a first N-type layer, manufactured on the first semiconductor substrate,
a first quantum dot layer, manufactured on the first semiconductor substrate, and located between the first P-type layer and first N-type layer, wherein a first level of electric current, at a first voltage, when present, is sufficient to cause the first quantum dot layer to emit near infrared electromagnetic radiation that includes at least a first frequency,
a first metal layer, manufactured on the first semiconductor substrate, wherein a first side of the first metal layer is in electrical contact with the first N-type layer, and a second side of the first metal layer faces a cytoplasm of the first cell,
a second metal layer, manufactured on the first semiconductor substrate, wherein a first side of the second metal layer is in electrical contact with the first P-type layer, and a second side of the second metal layer faces the cytoplasm of the first cell,
a first enzyme layer, coating the second side of the first metal layer with a first enzyme, wherein the first enzyme is activated, to produce electrons, by a first concentration of a first biochemical substance, within the cytoplasm of the first cell, that is at least a first threshold level, and
a second enzyme layer, coating the second side of the second metal layer with a second enzyme, wherein the electrons produced by the first enzyme layer form at least part of the first level of electric current, and at least part of the first voltage, when they are received by, and activate, the second enzyme layer;
placing the first intracellular monitoring device inside the first cell;
receiving via bioelectrocatalysis inside the first cell and via the first enzyme layer and the second enzyme layer on the first semiconductor substrate on the first intracellular monitoring device inside the first cell, the first level of electric current at the first voltage on the first quantum dot layer,
the first quantum dot layer emitting the near infrared electromagnetic radiation that includes at least the first frequency;
collecting at a first antenna, located outside the first cell, the emitted near infrared electromagnetic radiation from of the first intracellular monitoring devices, wherein a first portion of the near infrared electromagnetic radiation collected is from the first quantum dot layer; and
detecting on an optical domain frequency analyzer, coupled to the first antenna, at least, a presence of the first frequency in the near infrared electromagnetic radiation collected by the first antenna in order to produce a first frequency specific output representative of cell data for the first cell captured by the first intracellular monitoring device including a detected level of the first biochemical substance of interest inside the first cell.