Search for: All records

Abstract Cellular biophysical metrics exhibit systematic alterations during processes, such as metastasis and immune cell activation, which can be used to identify and separate live cell subpopulations for targeting drug screening. Image‐based biophysical cytometry under extensional flows can accurately quantify cell deformability based on cell shape alterations but needs extensive image reconstruction, which limits its inline utilization to activate cell sorting. Impedance cytometry can measure these cell shape alterations based on electric field screening, while its frequency response offers functional information on cell viability and interior structure, which are difficult to discern by imaging. Furthermore, 1‐D temporal impedance signal trains exhibit characteristic shapes that can be rapidly templated in near real‐time to extract single‐cell biophysical metrics to activate sorting. We present a multilayer perceptron neural network signal templating approach that utilizes raw impedance signals from cells under extensional flow, alongside its training with image metrics from corresponding cells to derive net electrical anisotropy metrics that quantify cell deformability over wide anisotropy ranges and with minimal errors from cell size distributions. Deformability and electrical physiology metrics are applied in conjunction on the same cell for multiparametric classification of live pancreatic cancer cells versus cancer associated fibroblasts using the support vector machine model. 

Abstract The use of engineered cells, tissues, and organs has the opportunity to change the way injuries and diseases are treated. Commercialization of these groundbreaking technologies has been limited in part by the complex and costly nature of their manufacture. Process-related variability and even small changes in the manufacturing process of a living product will impact its quality. Without real-time integrated detection, the magnitude and mechanism of that impact are largely unknown. Real-time and non-destructive sensor technologies are key for in-process insight and ensuring a consistent product throughout commercial scale-up and/or scale-out. The application of a measurement technology into a manufacturing process requires cell and tissue developers to understand the best way to apply a sensor to their process, and for sensor manufacturers to understand the design requirements and end-user needs. Furthermore, sensors to monitor component cells’ health and phenotype need to be compatible with novel integrated and automated manufacturing equipment. This review summarizes commercially relevant sensor technologies that can detect meaningful quality attributes during the manufacturing of regenerative medicine products, the gaps within each technology, and sensor considerations for manufacturing.