Apparatus, method, and system for the automated imaging and evaluation of embryos, oocytes and stem cells

1. A method for automated imaging and evaluation of human embryos, oocytes, or pluripotent cells with an imaging system, the method comprising:

receiving a multi-well culture dish comprising a plurality of micro-wells on a stage of the imaging system, wherein the plurality of micro-wells contain a plurality of human embryos or pluripotent cells, wherein the imaging system comprises-at least one time-lapse microscope inside a housing;

initializing the imaging system, wherein initializing the imaging system comprises:

generating an initial image of the multi-well culture dish with the imaging system;

detecting the presence of the multi-well culture dish on the stage of the imaging system;

generating an estimate of a position and an orientation of the plurality of micro-wells, wherein generating the estimate of the position and the orientation of the plurality of micro-wells comprises:

generating an initial estimate of micro-well position and orientation;

generating a refined estimate of micro-well position and orientation; and

determining the position and orientation of the micro-wells in a rotated coordinate system;

providing an alignment indication, wherein the alignment indication comprises a first indication if the multi-well culture dish is properly aligned and a second indication if the multi-well culture dish is improperly aligned;

automatically illuminating the multi-well culture dish with an illumination source of the at least one time-lapse microscope when the multi-well culture dish is properly aligned; and

automatically focusing the at least one time-lapse microscope configured to capture time-lapse images of the multi-well culture dish when the multi-well culture dish is properly aligned;

acquiring time-lapse images of the multi-well culture dish with a camera of the at least one time-lapse microscope; and

analyzing the time-lapse images of the multi-well culture dish to determine a development potential of at least one human embryo or pluripotent cell.

2. The method of claim 1 , wherein initializing the imaging system further comprises determining occupancy of a plurality of micro-wells in the multi-well culture dish.

3. The method of claim 1 , further comprising determining parameters related to the development potential of the at least one human embryo or pluripotent cell; and displaying the images captured by the at least one time-lapse microscope in a graphical user interface accessible by a touch-screen panel.

4. The method of claim 3 , wherein the parameters include a duration of first cytokinesis.

5. The method of claim 1 , wherein the alignment indication comprises a visual feedback comprising a color coded LED.

6. The method of claim 1 , wherein generating the initial estimate of micro-well position and orientation comprises:

retrieving a template, wherein the template represents at least a portion of the plurality of micro-wells included in the multi-well culture dish;

rotating the template through a series of predetermined positions;

generating a normalized cross-correlation between the initial image and the template in each of the series of predetermined positions;

identifying one of the series of predetermined positions of the template with the highest normalized cross-correlation score; and

identifying the initial estimate of the micro-well position and orientation as the position and orientation of the template in the one of the series of predetermined positions of the template with the highest normalized cross-correlation score.

7. The method of claim 1 , wherein generating the refined estimate of micro-well position and orientation comprises:

selecting a first set of features from the initial image, wherein the first set of features from the initial image correspond to a set of features of the multi-well culture dish;

generating vectors between adjacent pairs of features of the first set of features from the initial image; and

combining the vectors to determine the orientation of the multi-well culture dish.

8. The method of claim 1 , wherein providing an alignment indication comprises determining an initial alignment of the multi-well culture dish by detecting the relative position of an indexing feature of the multi-well culture dish with respect to a feature of the stage of the imaging system.

9. A method for automated imaging and evaluation of human embryos, oocytes, or pluripotent cells with an imaging system, the method comprising:

receiving a multi-well culture dish comprising a plurality of micro-wells on a stage of the imaging system, wherein the plurality of micro-wells contain a plurality of human embryos or pluripotent cells, wherein the imaging system comprises-at least one time-lapse microscope inside a housing;

initializing the imaging system, wherein initializing the imaging system comprises:

generating an initial image of the multi-well culture dish with the imaging system;

detecting the presence of the multi-well culture dish on the stage of the imaging system;

determining occupancy of a plurality of micro-wells in the multi-well culture dish, wherein determining occupancy of a plurality of micro-wells included in the multi-well culture dish comprises:

selecting at least one of the plurality of micro-wells;

identifying pixels located in the selected at least one of the plurality of micro-wells;

determining the intensity of the identified pixels;

comparing the intensity of the identified pixels to a brightness threshold;

determining a percent of pixels in the at least one of the plurality of micro-wells that exceed the brightness threshold; and

identifying the at least one of the plurality of micro-wells as occupied if the percent of pixels is greater than a threshold value;

providing an alignment indication, wherein the alignment indication comprises a first indication if the multi-well culture dish is properly aligned and a second indication if the multi-well culture dish is improperly aligned;

automatically illuminating the multi-well culture dish with an illumination source of the at least one time-lapse microscope when the multi-well culture dish is properly aligned; and

automatically focusing the at least one time-lapse microscope configured to capture time-lapse images of the multi-well culture dish when the multi-well culture dish is properly aligned;

acquiring time-lapse images of the multi-well culture dish with a camera of the at least one time-lapse microscope; and

analyzing the time-lapse images of the multi-well culture dish to determine a development potential of at least one human embryo or pluripotent cell.