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San Francisco, CA, United States

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 203.58K | Year: 2009

DESCRIPTION (provided by applicant): The detection and analysis of rare cells is a pervasive challenge in cellular biology and clinical diagnostics. Fluxion Biosciences proposes the development of a high throughput instrument and microfluidic consumable to conduct rare cell isolations for research and clinical applications. Targeted cell isolations are important to numerous fields such as cancer research, stem cell biology, prenatal care and immunological disorders. Quantifying the number of circulating tumor cells in the bloodstream is one such application that can lead to early cancer detection and can help monitor disease progression during treatment. These cells occur as low as one in ten million cells. Other compelling applications requiring rare cell detection include screening fetal cells during pregnancy for genetic aberrations and performing CD4 counts for immunocompromised patients with HIV. Modern laboratory tools such as centrifuges, cell sorters and cytometers are poorly equipped to detect and analyze cells appearing in such low frequencies. Although many kits are commercially available for conducting routine cell separations, most exhibit very poor recovery and purity yields when it comes to low prevalence target cells. This proposal aims to develop a microfluidic chip for rare cell isolations using the Company's well-plate microfluidic technology. The proposed research entails use of laminar flow streams to create efficient and accurate cell separations with high recovery and purity of targeted cells. The resultant product will deliver an automated, high throughput platform for conducting rare cell isolations on the research and clinical settings. Fluxion's approach represents a significant breakthrough over existing technologies which are mainly confined to low throughput, low efficiency cell isolations performed in filtration columns or well plates. The proposed system also enables multiple downstream analysis options with minimal cell handling and trauma. Cells will be available directly in the microfluidic devices for microscopic observation, high content screening and automated detection using a fluorescence plate reader. Cells will be easily removable from the devices for further analysis such as RT-PCR. Clinicians and researchers will be able to leverage this versatility of analysis and high throughput, high efficiency cell sorting to greatly enhance their productivity in life saving discoveries, diagnoses and treatments. PUBLIC HEALTH RELEVANCE: An unfortunate aspect of cellular biology is that the cells which hold the most promise for clinical diagnosis, disease progression and biological understanding often occur in the lowest frequencies. Circulating tumor cells can aid in the early detection and treatment of cancer yet appear as only one in ten million cells. A similar low prevalence is true for fetal cells found in the maternal bloodstream which could offer noninvasive ways to screen for genetic disorders earlier in pregnancy. Modern laboratory tools such as centrifuges, cell sorters and cytometers are simply not equipped to detect and analyze cells appearing in such low frequencies. This proposal aims to develop a high throughput system to isolate rare cells from biological samples and provide a range of analysis options to accommodate the desired endpoints of both clinical and research applications.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 635.98K | Year: 2007

DESCRIPTION (provided by applicant): Phase 2 Application: 1 R43 GM075509-01 Principle Investigator: Khine, Michelle High Throughput Intracellular Drug Screening Platform Rapid well-controlled intracellular delivery of compounds into a cell - without permanent damage to the cell - is a pervasive challenge in basic cell biology research as well as in drug discovery. The goal for this Phase II project is to continue to further develop a versatile drug-screening bench-top electroporation platform to address this ubiquitous need of academic and bio/pharmaceutical researchers. Our system - developed solely from the Phase 1 grant -- includes a control interface, with disposable 96-well microfluidic chips, that enables cells to each be controlled, monitored and manipulated individually. This platform also enables real-time electrical and optical monitoring of each cell's response. Three important and widely used applications that our system can uniquely address are: (1) drug safety testing via hERG screening (2) integrated transfection of an ion channel construct and ion channel recordings via patch clamp measurements and (3) intracellular delivery of short interfering RNA (siRNA) for target identification and validation. Awardment of this Phase 2 grant would allow us to continue to further develop our single-cell electroporation platform, making intracellular delivery a well-controlled, highly efficient, and parallel process. Phase 2 Application: 1 R43 GM075509-01 Principle Investigator: Khine, Michlle High Throughput Intracellular Drug Screening Platform Project Narrative In the Phase I portion of this grant, we developed a reliable bench-top single-cell microfluidic electroporation platform in a 96-well format. We demonstrated that this system could be used to permeate the cell membranes of an array of suspension cells in a controllable manner. We aim to further develop our platform for its original application as well as for its newfound applications (hERG screening, transfecting/patching, and siRNA delivery) by integrating our platform with electrophysiology capabilities as well as improving its throughput and lowering its required reagent volumes.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 117.70K | Year: 2008

DESCRIPTION (provided by applicant): Fluxion Biosciences, a leading bioanalytical instrumentation company, proposes a novel, high throughput instrument and microfluidic well-plate for biofilm research and drug discovery. Microbial biofilms present a major clinical challenge and a serious risk to patients, but research in this area has been traditionally hindered by limited ability to study biofilms under physiologically relevant conditions. These accumulations of microorganisms, which form a slimy, polysacc haride matrix, are involved in nearly 80% of infections. As such, biofilm efficacy of antimicrobial compounds is a major focus of drug discovery and research efforts at pharmaceutical, biotech, and research institutions. Fluxion Biosciences is proposing a novel approach to studying biofilms under physiological flow conditions. The proposed instrument will offer researchers and drug discovery scientists a means to study the efficacy of anti- microbial compounds on physiological relevant biofilm formations. T he system will be able to provide kinetic and endpoint analyses using a convenient, easy to use microplate format. Further analyses will be conducted using conventional microplate readers, offering a significantly higher throughput than current approaches. The instrument proposed here comprises a bench top system and consumable, 96-well microplate capable of running up to 48 simultaneous biofilm experiments under continuous flow. The results will be assayed using standard microplate readers for improved thr oughput. This represents a considerable breakthrough over existing technologies. Conventional flow cells require long setup times and are typically run in very low throughput. Well plate assays can be run in higher throughput, but ca not offer flow based e nvironments. Biofilms can be 100-1000 times more resistant than their planktonic (free-floating) counterparts, which makes traditional well plate assays a limited surrogate for anti-biofilm efficacy. The approach proposed by Fluxion involves coupling the a dvantages of flow-cell chambers (high biological relevance) with the convenience and throughput of traditional well plates. The resultant product will deliver an automated platform for biofilm research and anti-microbial drug discovery. Along with convenie nce and throughput, this system will deliver powerful features specific to biofilm analysis and drug discovery. These include a microfluidic dilution system for performing multiplexed dose-response analyses on anti-microbial compounds. The proposed system will be a simple to use, automated bench top platform which will have a significant impact on the study of biofilms, the disease conditions where they are found, and the drug compounds which are needed to address them in the clinical setting. Public Health Significance: Biofilms account for over 80% of microbial infections in the human body, and are a major focus of research and drug discovery efforts. Despite their widespread clinical impact, the instrumentation and screening tools available to study biofi lms are severely limited in throughput and effectiveness. Fluxion Biosciences proposes a novel microfluidic instrument and consumable microplate to offer significant increases in throughput and physiological relevance for anti-microbial drug discovery and research.

Apparatus and methods are provided for analysis of individual particles in a microfluidic device. The methods involve the immobilization of an array of particles in suspension and the application of experimental compounds. Such methods can also include electrophysiology studies including patch clamp recording, electroporation, or both in the same microfluidic device. The apparatus provided includes a microfluidic device coupled to a multi-well structure and an interface for controlling the flow of media within the microchannel device.

Fluxion Biosciences Inc. | Date: 2011-07-14

Methods, microfluidic devices, and instruments for magnetic separation of particles from a fluid are described. Examples include microfluidic devices having a removable portion. Examples include microfluidic devices having one or more regions of reduced fluid velocity. Examples further including instruments having pneumatic interfaces. Examples further includes instruments having controllable magnets, imaging components, or combinations thereof.

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