Cell DIVE™ is a powerful and innovative commercial technology platform that enables a researcher to analyze single 5 um tissue section with up to 60 biomarker stains. This platform has been developed over 10 years with a technically diverse team and multiple external collaborators. The process involves iteratively staining, imaging and inactivating a single tissue slide with sequential rounds of dye-labeled antibodies. Our multidisciplinary team has developed custom imaging software and algorithms including image registration, quality, cross-microscope calibration and down-stream image processing including image correction and cell segmentation.
As we developed this platform and understood our customer and collaborator needs, we focused on microscope calibration as an essential component of data quality and the development of a common reference standard. Our approach is to use reference values or idealized models for each calibration parameter and calibrate each microscope relative to these parameters. The reference values do not change and therefore each microscope can be considered independently and calibrated independently to the standard. Periodic checks or routine automated calibrations can then be used to determine if any of the calibration parameters have deviated too far from their calibrated values, and recalibrate if necessary. This robust calibration scheme was accomplished through the use of custom calibration plates that contained the appropriate targets. Mechanical, optical, and geometric calibrations were developed using the calibration plate (as the target), custom scripts and custom algorithms.
Today, our Cell DIVE platforms and workflows are available as a service (MultiOmyx™ with Neogenomics) and are increasingly sought after by research labs, as interest in multiplexing and multi-marker and single cell analysis grows.
The key differentiating aspect of this technology platform is the unique assembly and integration of biology, software, precision imaging and registration and high quality registered images for downstream processing. It relies on custom software, algorithms, and robust calibrations to efficiently image the biological sample and define/structure the incoming data to enable image stitching, registration between the iterative staining/bleaching rounds, and image analysis. The geometric inter-microscope calibrations ultimately enables imaging of multiple rounds across microscopes and registration of the images. As the biomedical research shifts from genomics to cell biology and spatial analysis the Cell DIVE platform will hopefully play a critical role in defining cancer and disease mechanisms.
Capabilities utilized for Multiplexed Tissue Imaging Platform project
Working from the molecular scale through human health and disease by building novel technology solutions for cell analysis and imaging applicationsRead more
MEMS & Microsystems
Integrating and synchronizing complex measurements to operate in our customer's products within highly constrained environmentsRead more
Alex CorwinPrincipal Engineer, MicrosystemsProject Lead
Christine SurretteLead Biomedical Engineer, MicrosystemsElectronics & Sensing
Fiona GintyTechnology Manager, BiosciencesBiology & Applied Physics
Liz McDonoughResearch Scientist - BiosciencesBiosciences
Yousef Al-KofahiSenior EngineerComputer Vision
- Gerdes, M.J., Sevinsky, C.J., Sood, A., Adak, S., Bello, M.O., Bordwell, A., Can, A., Corwin, A., Dinn, S., Filkins, R.J. and Hollman, D., 2013. Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue. Proceedings of the National Academy of Sciences, 110(29), pp.11982-11987.
- Al-Kofahi, Y., Sevinsky, C., Santamaria-Pang, A., Ginty, F., Sood, A. and Li, Q., 2016, April. Multi-channel algorithm for segmentation of tumor blood vessels using multiplexed image data. In Biomedical Imaging (ISBI), 2016 IEEE 13th International Symposium on (pp. 213-216). IEEE.