US 12,130,219 B2
Method and system for evaluating fertility of human spermatozoa
Itay Barnea, Petach Tikva (IL); Natan Tzvi Shaked, Mazkeret Batya (IL); Lidor Karako, Tel Aviv (IL); Michal Balberg, Tel Aviv (IL); and Alon Shalev, Tel Aviv (IL)
Assigned to TECHNOLOGY INNOVATION MOMENTUM FUND (ISRAEL) LIMITED PARTNERSHIP, Tel Aviv (IL)
Appl. No. 16/967,033
Filed by TECHNOLOGY INNOVATION MOMENTUM FUND (ISRAEL) LIMITED PARTNERSHIP, Tel Aviv (IL)
PCT Filed Jan. 30, 2019, PCT No. PCT/IL2019/050118
§ 371(c)(1), (2) Date Aug. 3, 2020,
PCT Pub. No. WO2019/150365, PCT Pub. Date Aug. 8, 2019.
Claims priority of provisional application 62/625,040, filed on Feb. 1, 2018.
Prior Publication US 2021/0041336 A1, Feb. 11, 2021
Int. Cl. G01N 15/0205 (2024.01); G01N 33/487 (2006.01); G02B 21/00 (2006.01)
CPC G01N 15/0205 (2013.01) [G01N 33/48735 (2013.01); G02B 21/0056 (2013.01); G02B 21/0076 (2013.01)] 14 Claims
 
1. A method for evaluating fertility potential of a living sperm cell, the method comprising:
deriving, from at least one of two-dimensional and three-dimensional optical path delay image data of a non-stained living sperm cell, data indicative of one or more predetermined physio spatial parameters of the non-stained living sperm cell being inspected, by performing at least one of quantitative phase microscopy (QPM) and interferometric phase microscopy (IPM) measurement on said living sperm cell after passing said living sperm cell through one of the following assays: (a) sperm density gradient, (b) swim-up, (c) hyaluronic acid binding, and (d) magnetic sorting using annexin V microbeads, wherein each of said one or more predetermined physio spatial parameters comprises one or more of the following: surface area of the living sperm cell or an organelle thereof; dry mass of the living sperm cell or of an organelle thereof; an average optical path delay of a certain surface area on the living sperm cell or of an organelle thereof; a variance of optical path delay being calculated of surface area of a part of all of the living sperm cell or of an organelle thereof; a subtraction between an average optical path delay calculated upon an anterior portion of the head of the living sperm cell and an average optical path delay calculated upon a posterior portion of the head of the living sperm cell, each of said anterior and posterior portions comprising between 40 and 60 percent of the surface area of the head of the living sperm cell;
providing said data indicative of said one or more predetermined physio spatial parameters as input data to a classifier of the fertility potential of the non-stained living sperm cell based on a DNA fragmentation level of the living sperm cell, said classifier being defined by a predetermined classification function being a correlation function correlating between one or more predetermined physio spatial parameters of sperm cells and DNA fragmentation distribution in sperm cells, said classification function being predetermined based on a dataset of training sperm cell samples each characterized by measured one or more predetermined physio spatial parameters and respective DNA fragmentation levels derived from a DNA fragmentation assay;
applying said classification function to said one or more predetermined physio spatial parameters of the living sperm cell being inspected and determining an estimated DNA fragmentation level, inside said DNA fragmentation distribution, in said living sperm cell being inspected, the DNA fragmentation level being indicative of the fertility potential of the living sperm cell.