Lab-on-a-chip Flow Cytometer Using COlor-Space-Time (COST) Coding Method

DESCRIPTION (provided by applicant): Lab-on-a-chip flow cytometer using color-space-time (CoST) coding method NanoSort, LLC RESEARCH and RELATED Other Project Information 7. PROJECT SUMMARY Fluorescence-activated-cell-sorting (FACS) or flow cytometry enables clinicians and researchers to quantitatively characterize the physical (cell size, shape, granularity) and biochemical (DNA content, cell cycle distribution, cell surface markers, and viability) properties of cels. Besides its applications in basic research (e.g. immunology, cell and molecular biology), the instrument has allowed clinicians to detect and monitor the progression of diseases such as acute myeloid leukemia (AML) and HIV/AIDS. With the capability of high- throughput sorting to enrich biospecimens and extract rare cell types, a state-of-the-art flow cytometer makes it possible to conduct rare-event studies such as the identification or isolation of bacterial cells, stem cells, or tumor cells. However, today's flow cytometers face two chalenges that limit the ability to drastically reduce their cost and extend their day-to-day utilization to clinical settings. The first limit is that the system's architecture is highly inefficient in utilizing the increasing number of available fluorescent colors. In today's flow cytometer design, each fluorescent color requires a dedicated PMT and optics; and the cost, complexity, and risk of failure grow with the number of detection parameters. Secondly, there exists a huge price gap (2-3X price difference) between flow cytometers (that count cells) and FACS (that count and assort cells). FACS are mostly located in shared core facilities and operated by well-trained, PhD level specialists. There is a large demand for FACS that would increase if cell sorting were to become more accessible and affordable than it is now. Based on nearly 10 years of research of Professor Lo's group at UCSD, we will develop the lab-on-a-chip technology into products that can address the above two challenges. To facilitate the transformation, we will apply our patented game-changing technologies: 1) COlor-Space-Time (COST) coding method to detect multiple parameters using a single PMT. The COST technique fundamentaly changes the relationship between the system performance and the system complexity in all existing flow cytometers. We also propose a highly efficient and cost effective on-chip piezoelectric cell sorting technique with low shearing and high cell viability. Our proposed research includes the systematic study of post-sortingcell viability for lab-on-a-chip FACS system, a limiting problem for successful commercialization that is overloked by most research laboratories. The proposed Phase I research uses innovative approaches to transform a laboratory technology into commercial products that have a market of over 1B and the potential for an expanded market following the proposed cost reductions and functionality improvements. These technology and business goals will have a direct impact on basic research and clinical applications to enhance the health and wellbeing of the entire population. PUBLIC HEALTH RELEVANCE: Lab-on-a-chip flow cytometer using color-space-time (CoST) coding method NanoSort, LLC RESEARCH and RELATED Other Project Information 8. PROJECT NARRATIVE The proposed project aims to develop lab-on-a-chip flow cytometers that are high performance, easy to operate and maintain, and significantly lower cost than any flow cytometers or fluorescence-activated-cell- sorters (FACS) available today, thus providingthis broadly applicable technique to new settings in research and clinical practice. The research will transform the lab-on-a-chip technologies developed in Professor Lo's laboratory into products that meet the market needs in advanced biomedical researchand point-of-care clinics. The proposed system substantially extends the original university technology with the invention of the COlor- Space-Time (COST) coding technique which allows multi-parameter detection using a single photo multiplier tube (PMT) detector.