SBIR-STTR Award

Since the late 1980s national guidelines to confirm HIV-1 infection dictate the use of Western blot (WB) and indirect immunofluorescence assay (IFA) for diagnosis1. However, nucleic acid amplification tests (NAAT) may identify some infections earlier; reduce testing costs; permit HIV-2 and broader HIV-1 subtype detection; reduce provision of false-positive, false-negative, and indeterminate test results. NAAT is currently not recommended for screening since it is much more expensive and involves complex methodology. However, a low cost, rapid NAAT test at point of care would be useful in Sexually Transmitted Infection (STI) clinics or emergency rooms (where patients often do not return for tests results) or on labor and delivery wards for high-risk pregnant women who have not previously been tested. More frequent screening in all health care settings could increase the proportion of HIV-infected clients who learn their results and who could be linked to appropriate care. Micronic's goal is to develop a firstof- its-kind, low cost qualitative PCR assay for HIV provirus DNA detection that is automated within a closed system, disposable device and allows specimen in / result out processing at near patient point of care and in low resource settings. The intent is to sell this device at under $5 as compared to the $45 to $75 current NAAT tests cost. The assay strategy is as follows : DNA is extracted from a whole blood finger stick (20-50 microliter) specimen using fluidic and valve logic within a laminate polymer device and the eluted nucleic acid introduced directly into microchannels to rehydrate a dried PCR master mix. PCR is rapidly performed within the microchannels in under 10 minutes. The amplified product is fluorescently tagged by a FRET method and a positive result detected optically at the end of 40 thermal cycles. Successful completion of the phase I milestone of 10 copy HIV detection following device extraction and amplification will confirm the validity of our assay integration and closed device strategy.

Public Health Relevance:
In order to better identify and counsel persons with unrecognized HIV infection and link them to clinical and prevention services as well as further reduce perinatal transmission of HIV in the United States the CDC has recommended expanded screening. The most sensitive screening method is based upon detection of the nucleic acid testing but this approach is currently expensive and performed in reference laboratories. We propose the miniaturization and automation of nucleic acid testing methods to enable low cost, near patient testing.

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

Thesaurus Terms:
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Micronics' goal is to develop a first-of-its-kind, low cost qualitative PCR assay for HIV RNA detection that is automated within a closed system, disposable device in turn processed by a portable instrument; the system will allow specimen in / result out processing at near patient point of care and in low resource settings. Since the late 1980s, national guidelines to confirm HIV-1 infection dictate the use of Western blot (WB) and indirect immunofluorescence assay (IFA) for diagnosis1. However, nucleic acid amplification tests (NAAT) may identify some infections earlier; reduce testing costs; permit HIV-2 and broader HIV-1 subtype detection; reduce provision of false-positive, false-negative, and indeterminate test results. NAAT is currently not recommended for screening since it is much more expensive and involves complex methodology. However, a low cost, rapid NAAT test at point of care would be useful in Sexually Transmitted Infection (STI) clinics or emergency rooms (where patients often do not return for tests results) or on labor and delivery wards for high risk pregnant women who have not previously been tested. More frequent screening in all health care settings could increase the proportion of HIV-infected clients who learn their results and who could be linked to appropriate care. The intent is to sell this device at substantially reduced costs compared to the $45 to $75 current NAAT tests cost. The assay strategy is as follows : RNA is extracted from a whole blood finger or heel stick (20-50 microliter) specimen using fluidic and valve logic within a tooled cartridge device and the eluted nucleic acid introduced directly into microchannels for cDNA synthesis. The cDNA is fluidically transferred to a second set of microchannels to rehydrate a dried PCR master mix. PCR is rapidly performed within the microchannels in under 20-30 minutes. The amplified product is fluorescently tagged by a FRET method and a positive result detected optically at the end of 40 thermal cycles. Successful completion of the phase II milestones of 50 copy HIV detection following processing on a prototype totally integrated cartridge as run on a Micronics prototype base device initially for spiked blood specimens and then for retrospective positive HIV-1 specimens will develop the system through pre-clinical evaluations to a stage ready for follow-up clinical evaluations to generate data for FDA approval.

Public Health Relevance:
NARRATIVE In order to better identify and counsel persons with unrecognized HIV infection and link them to clinical and prevention services as well as further reduce perinatal transmission of HIV in the United States, the CDC has recommended expanded screening. The most sensitive screening method is based upon detection of the nucleic acid testing but this approach is currently expensive and performed in reference laboratories. We propose the miniaturization and automation of nucleic acid testing methods to enable low cost, near patient testing.

Public Health Relevance Statement:
NARRATIVE In order to better identify and counsel persons with unrecognized HIV infection and link them to clinical and prevention services as well as further reduce perinatal transmission of HIV in the United States, the CDC has recommended expanded screening. The most sensitive screening method is based upon detection of the nucleic acid testing but this approach is currently expensive and performed in reference laboratories. We propose the miniaturization and automation of nucleic acid testing methods to enable low cost, near patient testing.

NIH Spending Category:
Bioengineering; Clinical Research; Health Services; Prevention

Project Terms:
Accident and Emergency department; Acute; Agreement; Algorithms; Automation; base; Biological Assay; Blood specimen; Blood-Borne Pathogens; Bulla; Caring; Centers for Disease Control and Prevention (U.S.); Chemistry; Client; Clinic; Clinical; Collaborations; Complementary DNA; Complex; Computer software; Cooperative Research and Development Agreement; cost; Counseling; cross reactivity; Cytomegalovirus; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; DNA; Early Diagnosis; Energy Transfer; Fingers; follow-up; Funding; Goals; Gold; Guidelines; Healthcare; Heating; Heel; Hepatitis B Virus; Hepatitis C virus; high risk; HIV; HIV Infections; HIV-1; HIV-2; Housing; Human immunodeficiency virus test; Human Resources; Hybrids; improved; Indirect Fluorescent Antibody Technique; Infant; Infection; Injection of therapeutic agent; instrument; Laboratories; Learning; Link; Liquid substance; Logic; Methodology; Methods; Microfluidics; Miniaturization; Molds; Mothers; Nucleic Acid Amplification Tests; Nucleic Acids; Optics; Patients; Performance; Perinatal; Persons; Phase; point of care; pre-clinical; Pregnant Women; prenatal; Preparation; Prevention; Prevention Guidelines; prevention service; Price; Process; prototype; Proviruses; public health relevance; Publishing; Reagent; Recommendation; research clinical testing; Resolution; Resources; Reverse Transcription; RNA; RNA amplification; Running; Screening procedure; Serologic tests; Sexually Transmitted Diseases; Specificity; Specimen; Staging; System; Tandem Repeat Sequences; Test Result; Testing; Training; transmission process; United States; ward; Western Blotting; Whole Blood; Work