Sartorius Bioanalytical Instruments, Inc.

Essen Instruments, Inc.

National Research Council of Canada

Eric William Endsley

Kirk S Schroeder

Daniel Appledorn

Nevine Holtz

Bradley Neagle

Keith J Morton

Brad Neagle

David Rock

Michael T Kusner

Alan J Riggs

Kyle Schutte

Paul Joseph Bierdz

Systems and methods are provided for automatically imaging and analyzing cell samples in an incubator. An actuated microscope operates to generate images of samples within wells of a sample container across days, weeks, or months. A plurality of images is generated for each scan of a particular well, and the images within such a scan are used to image and analysis metabolically active cells in the well. Tins analysis includes generating a 'range image' by subtracting the minimum intensity value, across the scan, for each pixel from the maximum intensity value. This range image thus emphasizes cells or portions of cells that exhibit changes in activity over a scan period (e.g., neurons, myocytes, cardiomyocytes) while de-emphasizing regions that exhibit consistently high intensities when images (e.g., regions exhibiting a great deal of autofluorescence unrelated to cell activity).

Live cell visualization and analysis

An imaging apparatus is provided to facilitate epifluorescent imaging of three (or more) color channels and to perform phase contrast and/or bright field imaging of samples without manual adjustment of the imaging apparatus. This allows for automated imaging, over extended periods of time, of a plurality of samples by a device located inside an incubator without disturbing the incubator environment to manually adjust the apparatus. Also provided are embodiments to facilitate user swapping of removable optical modules and/or transillumination modules to allow the imaging apparatus to be adapted to different combinations of assays and/or fluorescent indicators so as to increase the variety of experiments and/or fluorescent dyes that can be imaged using the imaging apparatus.

Optical module with three or more color fluorescent light sources and methods for use thereof

Systems, methods, and apparatuses of controlling fluid flow are disclosed. An apparatus includes a first microplate having a first open portion and defining one or more first wells therein, a second microplate having a second open portion and defining one or more second wells therein, and a pneumatic lid constructed of styrene ethylene butylene styrene (SEBS). The pneumatic lid extends over the first open portion and the second open portion and includes one or more microfluidic channels that fluidly couple the one or more first wells to the one or more second wells. The pneumatic lid provides an airtight seal over the first microplate and the second microplate.

Methods and apparatus for perfusion and environment control of microplate lab ware

Systems and methods are provided for microscopically and fluorescently imaging cell-bearing biological samples or other samples of interest. A microscope objective or other optical elements that exhibits chromatic aberration can be used to obtain images of fluorophores or other contrast agents at different wavelengths. The obtained images are then used to correct each other, e.g., to remove artifacts in an image of a shorter-wavelength fluorophore that are caused by cross-talk from a longer-wavelength fluorophore. A longer-wavelength image, taken at a focal distance corresponding to the shorter-wavelength fluorophore, is taken and used to subtract the activity of the longer-wavelength fluorophore in the shorter-wavelength image. The longer-wavelength image may be taken using a microscope set to the shorter-wavelength focal distance. Alternatively, the longer-wavelength image may be simulated by applying a blurring filter or other methods to a longer-wavelength image taken when the microscope is set to the longer-wavelength focal distance.

Spectral unmixing

Methods and apparatus for perfusion and environment control of microplate labware

Growing community of inventors

Ann Arbor, MI, United States of America

Eric William Endsley