The NIST RMAT laboratory programs serve the regenerative medicine and advanced therapy community through the development of an innovative measurement infrastructure for complex biological systems, including enabling tools, methods and protocols, bioinformatics and modeling tools as well as documentary standards and reference materials. Cell counting methods, flow cytometry reference materials, experimental design for enhancing comparability in viability assays, rapid microbial testing, cell line authentication, and imaging algorithm testing for quantitative imaging of stem cells are some of the topics being investigated.
Cell Counting and viability are key measurements critical for decision making from R&D to manufacturing, but are known to have large measurement variabilities. We recently developed an approach for evaluating the quality of cell counting measurements through experimental design and statistical analysis. The NIST approach represents a paradigm shift from traditional approaches that rely largely on highly specific reference materials. In addition, the experimental design and statistical method is agnostic of the cell type and counting method, making it broadly applicable to many counting applications. A user interface is under development to allow broader adoption of this method as an international standard and a research tool.
Live Cell Imaging tools allow us to monitor spatial information and population heterogeneity on large numbers of individual cells. High quality data obtained using benchmark materials, may be used to develop predictive models based on stochastic fluctuations, provide reference data, and have the potential be used to validate putative molecular markers for pluripotency and differentiation, and for evaluating markers of product potency. We are also developing advanced measurement capabilities, including quantitative label-free imaging, such as broadband coherence RAMAN spectroscopy (BCARS) imaging, for characterizing cell state and cell-biomaterial interactions.
Flow Cytometry, while widely used in characterization of cell populations, is notoriously variable from instrument to instrument and location to location. We work with stakeholders to make flow cytometry a quantitative tool that can provide comparable data across labs by developing benchmarking materials and protocols including fluorescence standards for calibrating beads, and lyophilized cell reference materials.
Genome Editing products and processes need reliable methods for assuring the results of editing and adding confidence of safety and likely effectiveness. We are working with stakeholders, including through NIST-organized workshops, to identify precompetitive technology, measurement, and standards needs and solutions. The current program focuses on evaluating assays and informatics tools, and the development of next-generation reference materials. We have established a NIST-led Genome Editing Consortium to develop measurement solutions and standards to advance this technology space.