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Engineering  |  Center for Biosignatures Discovery Automation

The Cellarium Project

Isolation of cells in microfabricated chambers containing oxygen sensors.

Isolation of cells in microfabricated chambers containing oxygen sensors.

Determinants of human health and disease depend, ultimately, on the biological state of individual cells. Understanding distributions of key metabolic parameters at the single-cell level, in response to microenvironmental perturbations, holds the promise of facilitating new insights into underlying molecular pathways and biological mechanisms. Numerous applications in basic research, compound discovery and personalized medicine can benefit from enhanced understanding at the single cell level. Currently, a gap exists between this need and available analytical techniques in the domain of single cell analysis.

The “Cellarium” is a high throughput live-cell microarray screening technology that is being developed for dynamic, multiparameter sensing of single-cell metabolic phenotypes. The Cellarium array is comprised of individual chambers that are modestly larger than the cells of interest and a lid that is used to seal the entire array after cells are placed within the individual chambers. Once sealed, the microenvironment of the sealed chamber begins to change in response to cell metabolism. Sensors are placed within the chamber to enable measurement of these changes over time after sealing the chamber. As such, the Cellarium provides a means of measuring transmembrane fluxes. The key innovations of the Cellarium development effort are associated with integrating a chamber, sensors, a living cell and a sealing lid into a massively parallel array where each chamber is individually only about ~150 picoliters in volume!  Each chamber is approximately the diameter of an average human hair (~100 micrometers), and about one fifth of that diameter (~20 micrometers) deep. Cellarium sensors detect changes in metabolic parameters of interest using fluorescent sensors that are sensitive to analytes such as oxygen, pH and glucose. The Cellarium engineering team is integrating microfabrication technology, biological assay protocols, and measurement instrumentation to make these high throughput measurements possible for the first time. The Cellarium Project is addressing National Institutes of Health Common Fund priorities by extending the range of biosignatures available to the Library of Integrated Network- Based Cellular Signatures (LINCS) centers, and by developing a technology platform that that can be broadly disseminated within basic and applied sciences laboratories.

Single-cell analysis: representative oxygen metabolism data.

Figure 2. Single-cell analysis: representative oxygen metabolism data.

This research project is supported by the NIH Common Fund “Library of Integrated Network-Based Cellular Signatures” (LINCS) program by a U01 Technology grant to D. Meldrum, PI, entitled, “Live-Cell Microarray for High-Throughput Observation of Metabolic Signatures” and the NIH National Human Genome Research Institute (NHGRI) Center of Excellence in Genomic Sciences (CEGS) grant to D. Meldrum, PI, entitled “CEGS: Microscale Life Sciences Center.”