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State College, PA, United States

Grant
Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase I | Award Amount: 225.00K | Year: 2014

This Small Business Technology Transfer (STTR) Phase I project will demonstrate the feasibility of microfluidic-based, bio-compatible, bio-safe, fluorescence-activated cell sorters. Cell sorters are powerful, high-throughput, single-cell characterization and purification tools that are vital for labs in fields such as molecular biology, pathology, plant biology, stem cell biology, and medical diagnostics. Despite their significant impact, current commercial cell sorters have a variety of drawbacks. High instrument costs (average cost: ~$500,000), high maintenance (maintenance cost: ~$30,000 per year; highly trained personnel needed), significant biosafety concerns, and reduction of cell viability and functionality make conventional cell sorters less effective in many applications and inhibit their widespread use. To address limitations of existing cell sorters, an innovative approach is proposed that features two key technologies: 1) a "microfluidic drifting" based cell-focusing technique; and 2) a cell-deflection technique using chirped interdigitated transducers (IDTs). The proposed microfluidic cell sorter eliminates the generation of hazardous aerosols and preserves high cell viability and functions. The broader impact/commercial potential of this project, if successful, will be the development of the most bio-compatible and bio-safe cell sorters for researchers and scientists. According to a 2011 BCC research report, the instrument market for flow cytometers and cell sorters accounted for $1.4 billion in 2010 and is expected to grow at a CAGR of 9.8% from 2010 to 2015 ($2.2 billion). The served available market (SAM) is estimated to be ~$200 million. Compared with the existing cell sorters, the proposed microfluidic cell sorter will have the following advantages: 1) high bio-compatibility; 2) high bio-safety; and 3) low costs and low maintenance. In addition, the cell sorter will be more accessible to researchers and address existing unmet needs in the market (e.g., sorting fragile or sensitive cells while preserving high viability and functions). It will accelerate research findings and improve diagnostics and therapeutics. It will also create more job opportunities as the company grows.


Grant
Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase II | Award Amount: 750.00K | Year: 2015

The broader/commercial impact of the Small Business Technology Transfer (STTR) Phase II project will be a cell sorter, a new research tool for life science research, animal reproduction, and cell-based therapy. In the past decade, cell sorters have become vital in many fields, such as molecular and cellular biology, immunology, plant biology, animal reproduction, and medical diagnostics and therapeutics. Despite their significant impact, current cell sorters have the following drawbacks: high equipment and maintenance costs, significant bio-safety concerns, and reduced cell viability and function. These drawbacks reduce the effectiveness of cell sorters in many important research studies and clinical applications. Enabled by this innovation, researchers will be able to better understand the causes of diseases, identify new therapies, and test new drugs and vaccines. It also has the potential to improve dairy production efficiency, and aid medical doctors in making better decisions about diagnosis and treatment. In Phase II, the goal is to improve performance of the instrument, and validate the performance with end users. This STTR Phase II project will demonstrate the feasibility of a microfluidic-based, bio-compatible, bio-safe, fluorescence-activated cell sorter. Cell sorters are powerful, high-throughput, single-cell characterization and purification tools that are vital for labs in fields such as molecular biology, pathology, plant biology, stem cell biology, and medical diagnostics. The technology is based on acoustofluidic (i.e., the fusion of acoustics and microfluidics) cell sorting chips that preserve the integrity and functionality of sorted cells. Current cell sorting systems reduce cell viability, integrity, and cell function due to high shear stress, high impact force, and high driving voltage, which reduces their effectiveness as a research tool, and in clinical applications. Unlike current cell sorters that use electrostatic force to sort cells, which require 12,000 V of driving voltage, the proposed technology uses acoustic tweezers to sort cells, and requires only 10 V, which significantly reduces cell damage. Compared with existing cell sorters, the proposed microfluidic cell sorter will have the following advantages: 1) high bio-compatibility; 2) high bio-safety; and 3) lower costs and lower maintenance. In addition, the cell sorter will be more accessible to researchers and address existing unmet needs in the market (e.g., sorting fragile or sensitive cells while preserving high viability and function). This will accelerate research findings and improve diagnostics and therapeutics.


Chen Y.,Pennsylvania State University | Li S.,Pennsylvania State University | Gu Y.,Pennsylvania State University | Li P.,Pennsylvania State University | And 5 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2014

Cell enrichment is a powerful tool in a variety of cellular studies, especially in applications with low-abundance cell types. In this work, we developed a standing surface acoustic wave (SSAW) based microfluidic device for non-contact, continuous cell enrichment. With a pair of parallel interdigital transducers (IDT) deposited on a piezoelectric substrate, a one-dimensional SSAW field was established along disposable micro-tubing channels, generating numerous pressure nodes (and thus numerous cell-enrichment regions). Our method is able to concentrate highly diluted blood cells by more than 100 fold with a recovery efficiency of up to 99%. Such highly effective cell enrichment was achieved without using sheath flow. The SSAW-based technique presented here is simple, bio-compatible, label-free, and sheath-flow-free. With these advantages, it could be valuable for many biomedical applications. This journal is © The Royal Society of Chemistry 2014. Source


Chen Y.,Pennsylvania State University | Nawaz A.A.,Pennsylvania State University | Zhao Y.,Pennsylvania State University | Huang P.-H.,Pennsylvania State University | And 4 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2014

The development of microfluidic chip-based cytometers has become an important area due to their advantages of compact size and low cost. Herein, we demonstrate a sheathless microfluidic cytometer which integrates a standing surface acoustic wave (SSAW)-based microdevice capable of 3D particle/cell focusing with a laser-induced fluorescence (LIF) detection system. Using SSAW, our microfluidic cytometer was able to continuously focus microparticles/cells at the pressure node inside a microchannel. Flow cytometry was successfully demonstrated using this system with a coefficient of variation (CV) of less than 10% at a throughput of ~1000 events s-1 when calibration beads were used. We also demonstrated that fluorescently labeled human promyelocytic leukemia cells (HL-60) could be effectively focused and detected with our SSAW-based system. This SSAW-based microfluidic cytometer did not require any sheath flows or complex structures, and it allowed for simple operation over a wide range of sample flow rates. Moreover, with the gentle, bio-compatible nature of low-power surface acoustic waves, this technique is expected to be able to preserve the integrity of cells and other bioparticles. This journal is © The Royal Society of Chemistry 2014. Source


Chen Y.,Pennsylvania State University | Li P.,Pennsylvania State University | Huang P.-H.,Pennsylvania State University | Xie Y.,Pennsylvania State University | And 4 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2014

Rare cells are low-abundance cells in a much larger population of background cells. Conventional benchtop techniques have limited capabilities to isolate and analyze rare cells because of their generally low selectivity and significant sample loss. Recent rapid advances in microfluidics have been providing robust solutions to the challenges in the isolation and analysis of rare cells. In addition to the apparent performance enhancements resulting in higher efficiencies and sensitivity levels, microfluidics provides other advanced features such as simpler handling of small sample volumes and multiplexing capabilities for high-throughput processing. All of these advantages make microfluidics an excellent platform to deal with the transport, isolation, and analysis of rare cells. Various cellular biomarkers, including physical properties, dielectric properties, as well as immunoaffinities, have been explored for isolating rare cells. In this Focus article, we discuss the design considerations of representative microfluidic devices for rare cell isolation and analysis. Examples from recently published works are discussed to highlight the advantages and limitations of the different techniques. Various applications of these techniques are then introduced. Finally, a perspective on the development trends and promising research directions in this field are proposed. © 2014 The Royal Society of Chemistry. Source

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