METHODS FOR SELECTING CELLS WITH ENHANCED GROWTH AND PRODUCTION PROPERTIES
The disclosure relates generally to cell biology and more specifically to mechanical manipulation of cells. Methods are provided which allow robotic devices to select cell colonies that have optimum growth and bioproduction qualities resulting in a collection of cell lines that have a much higher proportion of desired growth and production characteristics. These methods greatly reduce the time and effort needed to identify cell lines with optimum combinations of viability, growth and bioproduction properties. In some embodiments, the robotic device is able to measure multiple characteristics of the colonies and use these results to select the desired colonies.
1 . A method for automated selecting of colonies of cells producing a molecule of interest, the method comprising:
a) providing cell colonies in a semi-solid medium or on a substrate;
b) contacting the cells with a label capable of binding the molecule of interest;
c) placing the cell colonies in a robotic device having an image capturing function;
d) imaging the cell colonies using white light and at a wavelength of light passed by a narrow bandwidth filter;
e) selecting cell colonies having a size greater than a desired minimum size based on the white light image; and
f) selecting from the population of cell colonies having the desired minimum size based on the white light image, cell colonies having a size greater than a minimum size based on the narrow bandwidth filtered image.
2 . The method of claim 1 , further comprising picking the cell colonies selected in step f, and transferring them to a multi-well culture plate.
3 . The method of claim 2 , wherein the label is a fluorescent or luminescent label having an emission wavelength.
4 . The method of claim 3 , wherein the wavelength of light passed by the narrow bandwidth filter corresponds to the emission wavelength of the fluorescent or luminescent label.
5 . The method of claim 2 , wherein the cell colonies are provided in a semi-solid medium.
6 . The method of claim 2 , wherein the cell colonies are provided on a substrate.
7 . The method of claim 3 , wherein the fluorescent label is selected from the group consisting of a fluorescein, a rhodamine, a Texas Red, and a fluorescein isothiocyanate (e.g., fluorescein-5-isothiocyanate).