SBIR-STTR Award

The long-term objective of this proposed research is to develop a simple, inexpensive point-of-care device that will purify CD4+ T cells from whole blood and perform absolute CD4+ T cell counts. This will be accomplished by adapting, combining, and testing a prototype chip-based flow-through particle counter with a separate passive microfluidic cell separation and purification technique. Toward this objective, Phase I will investigate four aims focused on establishing a proof-of-concept system using these technologies to count CD4+ T cells. Aim One will determine the feasibility of using a CD4 passive microfluidic "prep card" capable of purifying CD4+ T cells from whole blood. Aim Two will determine the feasibility of using microfabricated chips to count the isolated ceils in a disposable platform. Aim Three will determine the feasibility of using a simple electronic interface to reliably count the CD4+.T cells. Aim Four will test and validate the individual CD4 counting components using commercially available normal blood specimens. Upon completion of these four aims, Phase II will focus on integrating the microfluidic separation "prep card" with the microfabricated counter chips to produce a single component, one-time use CD4 counter cartridge. This new system will then undergo further validation and optimization in preparation for field trials against existing industry gold standards for CD4 analysis. The resulting device, when fully validated and evaluated in the proposed scenarios of use, will be simple, robust, and unique in that it provides a fully quantitative CD4+ T cell analysis with an instrument costing less than $300. This is almost two orders of magnitude below the cost of established flow cytometry devices. Reagent and disposable costs will also be lower than that of any currently available device. The tool will find immediate application in all levels of the public health care system, particularly in resource-poor areas and developing countries, for monitoring persons with human immunodeficiency virus (HIV), formulating differential diagnoses, and making therapeutic decisions regarding anti-retroviral drug treatment regimes, including the highly active anti-retroviral therapy (HAART) approach.

Thesaurus Terms:
Biomedical Equipment Development, Cell Sorting, Clinical Biomedical Equipment, Helper T Lymphocyte, Leukocyte Count, Microfluidics, Portable Biomedical Equipment Hiv Infection, Consumable /Disposable Biomedical Equipment, Cost Effectiveness, Electrical Impedance, Evaluation /Testing, Monocyte Bioengineering /Biomedical Engineering, Clinical Research, Flow Cytometry, Human Tissue, Immunomagnetic Separation, Microarray Technology, Microprocessor /Microchip

The long-term objective of this proposed research is to develop a simple, inexpensive point-of-care device that will perform absolute and percent CD4+ T cell counts from whole blood. This will be accomplished by adapting and testing a novel ""hybrid"" approach to microfluidic sample preparation and analysis. One-time use thin-film laminated microfluidic cassettes will collect, count, and store the blood sample while the required cocktail reagents will be stored and injected into the cassettes from a bench-top unit. The integrated system will perform a total white blood cell count, absolute CD4+ T cell count, and percent CD4 count using a new volumetric combination electric impedance/fluorescence sensor contained on a disposable microfluidic cassette. Toward this objective, Phase II will expand on our Phase I effort and focus on system optimization and validation. Aim one will optimize the microfluidic cassette design and CD4 blood labeling protocol for automated, on-card CD4+ T cell counting. Aim two will focus on fabrication and testing of the integrated bench-top system. Aim three will test and validate the completed CD4 enumeration system, using both modified commercially available normal human whole blood and clinical samples from HIV+ patients, and begin the bench-top studies required to obtain FDA clearance for a Class II medical device. The resulting device, when fully validated and evaluated in the proposed scenarios of use, will be simple, robust, and unique in that it provides a fully quantitative CD4+ T cell analysis with an instrument costing less than $1000. This is many times below the cost of established flow cytometry devices. Reagent and disposable costs will also be lower than that of any currently available device with per-test total costs of less than $1.50. The tool will find immediate application in all levels of the public health care system, particularly in resource-poor areas and developing countries, for monitoring persons with human immunodeficiency virus (HIV), formulating differential diagnoses, and making therapeutic decisions regarding anti-retroviral drug treatment regimes, including the highly active anti-retroviral therapy (HAART) approach. PUBLIC HEALTH RELEVANCE The successful completion of an inexpensive, portable CD4 counter would constitute a significant breakthrough in HIV monitoring and treatment by offering healthcare providers a less expensive, mobile platform to conduct the most common CD4 diagnostic test currently performed in the world. Such a breakthrough will dramatically improve testing efficiencies with its single-use, disposable test cartridges and will make it possible to rapidly test patients at bedside, in remote locations, or in areas with limited healthcare resources. Finally, this new point-of-care system could significantly reduce current CD4 equipment and per-test costs, thereby resulting in millions of dollars saved in the US healthcare and insurance industries, with even greater worldwide healthcare impacts in developing countries.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
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