US 12,467,918 B1
Systems and methods for measuring changes in cellular activity in live tissue
Michael Korrer, Madison, WI (US); Pichet Adstamongkonkul, Madison, WI (US); T.S. Ramasubramanian, Madison, WI (US); Scott Johnson, Madison, WI (US); and Sean Caenepeel, Madison, WI (US)
Assigned to Elephas Biosciences Corporation, Madison, WI (US)
Filed by Elephas Biosciences Corporation, Madison, WI (US)
Filed on Jan. 27, 2025, as Appl. No. 19/038,526.
Claims priority of provisional application 63/743,964, filed on Jan. 10, 2025.
Int. Cl. G01N 33/574 (2006.01); C12N 5/078 (2010.01); G01N 33/48 (2006.01); G01N 33/50 (2006.01); G01N 33/68 (2006.01)
CPC G01N 33/5047 (2013.01) [C12N 5/0634 (2013.01); G01N 33/48 (2013.01); G01N 33/574 (2013.01); G01N 33/6854 (2013.01); C12N 2503/02 (2013.01); G01N 2333/70521 (2013.01); G01N 2333/70532 (2013.01); G01N 2333/70578 (2013.01); G01N 2333/70596 (2013.01); G01N 2500/10 (2013.01)] 19 Claims
 
1. A method of measuring cellular activity in a tissue sample, comprising
obtaining a tissue sample comprising living tumor cells derived from a biopsy of a human cancer patient,
wherein the biopsy is a core needle biopsy and/or a forceps biopsy;
obtaining a tissue section from the obtained tissue sample,
wherein the tissue section comprises living tumor cells,
wherein the tissue section comprising living tumor cells has a length between 100 μm to 8.81 mm,
wherein the tissue section comprising living tumor cells has an approximate width between approximately 100 μm to 3 mm;
wherein the tissue section comprising living tumor cells has an approximate height between approximately 100 μm to 1 mm;
exposing the tissue section to a first stimulus at a first time point, wherein the first stimulus is a control stimulus comprising standard culture conditions suitable for maintaining viability of the tissue section;
measuring cellular activity in the tissue section during and/or after exposure to the first stimulus;
further exposing the tissue section to a second stimulus at a second time point after the first time point, wherein the second stimulus is an immune checkpoint inhibitor (ICI) added to the tissue section under standard culture conditions suitable for maintaining viability of the tissue section;
measuring one or more cellular activities in the tissue section during and/or after exposure to the second stimulus;
determining changes in cellular activity within the tissue section based on 1) the cellular activity measurements before the second time point, and during and/or after the first time point, and 2) the cellular activity measurements during and/or after the second time point;
wherein the tissue section comprises living immune cells;
wherein measuring the one or more cellular activities comprises measuring immune cell activity within the tissue section.