SBIR-STTR Award

The overall goal of this Phase I SBIR proposal to prove the feasibility of developing a rapid (<20 minute), CLIA-waived, fully automated, molecular diagnostic technology for the multiplexed detection of two sexually transmitted infections (STIs). ?Chlamydia trachomatis (CT) and ?Neisseria gonorrhoeae (NG) infections are the number one and two most commonly reported bacterial STIs, with an estimated 131 million and 78 million new cases annually of CT and NG, respectively worldwide. These infections are curable with antibiotics, however no rapid, accurate diagnostic test is available to inform clinical treatment decisions during the patient visit. Untreated infections lead to serious sequelae including pelvic inflammatory disease (PID) and its associated complications, such as ectopic pregnancy, infertility, and chronic pelvic pain. Furthermore, loss to follow-up is a significant problem with STI patients. Therefore, ?timely diagnosis using accurate diagnostics and early treatment is imperative?. Rapid, immunoassay based point-of-care (POC) tests for CT/NG fail to diagnose more than 50% of Chlamydia positive cases. Nucleic Acid Amplification Tests (NAATs) are the current gold standard for diagnosing CT/NG due to their high sensitivity and specificity. However the only FDA approved POC NAAT for CT/NG is expensive and takes more than 90 minutes for diagnosis. As such ?there is great need for an effective POC diagnostic test for CT/NG. ?Specific Aims: The Phase I deliverable of this project will be to validate a 20 minute POC NAAT for CT/NG in a clinical setting. In Aim 1, room temperature stable lyophilized reagents will be implemented on the device. In Aim 2, the sample-to-answer assay will be developed and validated for clinical samples. Finally in Aim 3, the POC test device for CT/NG will be evaluated by the clinician end-user, in an actual clinical setting, using freshly collected patient samples. With a projected cost-of-goods of under $5, our miniaturized molecular diagnostic device will address the need for affordable portable tests that enable accurate, detection and treatment of multiple STDs in lab-free, point of care settings.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE STATEMENT Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are easily cured with antibiotics, however since most cases are asymptomatic, they often go undiagnosed and untreated. Untreated infections lead to serious sequelae including pelvic inflammatory disease (PID) and its associated complications, such as ectopic pregnancy, infertility, and chronic pelvic pain. Timely diagnosis using effective point-of-care diagnostics and early treatment is necessary. We propose to develop a 20-minute, automated, multiplex nucleic acid amplification test for CT/NG to enable rapid testing and treatment of infected individuals in a single visit.

Project Terms:
Address; Antibiotics; Automation; base; Bedside Testings; Biological Assay; Buffers; Cells; Chemistry; Chlamydia; Chlamydia trachomatis; chronic pelvic pain; Clinic; Clinical; Clinical Sensitivity; Clinical Treatment; Collection; cost; Cytolysis; Data; design; Detection; Device Designs; Devices; Diagnosis; diagnosis standard; Diagnostic; Diagnostic tests; Early treatment; Ectopic Pregnancy; Ensure; Evaluation; FDA approved; Female; follow-up; Freeze Drying; Goals; Gold; Gonorrhea; hospital laboratories; Human; Immunoassay; Individual; Infection; Infertility; Lateral; Lead; male; microdevice; Microfluidics; miniaturize; molecular diagnostics; multiplex detection; Neisseria gonorrhoeae; novel; Nucleic Acid Amplification Tests; Nucleic Acids; Patients; Pelvic Inflammatory Disease; Performance; Phase; point of care; point-of-care diagnostics; portability; preclinical evaluation; Preparation; Process; programs; Protocols documentation; public health relevance; Reagent; Reference Standards; Rehydrations; Reporting; research clinical testing; Resources; Sampling; Sensitivity and Specificity; Sexually Transmitted Diseases; Small Business Innovation Research Grant; Swab; System; Technology; Temperature; Testing; Time; Tube; Urine; usability; Visit

Building on the successes of our Phase 1 SBIR project, we propose to refine and productize our sample-to-answer CT/NG NAAT and to validate the analytical and clinical performance of the assay in the intended use setting in Phase 2 of this SBIR project. ?Chlamydia trachomatis (CT) and ?Neisseria gonorrhoeae ?(NG) infections are the number one and two most commonly reported bacterial sexually transmitted infections (STI) respectively, with an estimated 2.86 million new CT cases and 820,000 new NG cases in the US each year, and associated costs exceeding $1 Billion. Both infections are curable with antibiotics, however no CLIA waved, rapid, accurate diagnostic test is available to inform clinical treatment decisions during the patient visit. Untreated infections lead to serious sequelae including pelvic inflammatory disease (PID) and its associated complications, such as ectopic pregnancy, infertility, and chronic pelvic pain. Furthermore, loss to follow-up is a significant problem with STI patients. Therefore, timely diagnosis using accurate diagnostics and early treatment is imperative. Rapid, immunoassay based point-of-care (POC) tests for CT/NG fail to diagnose more than 50% of Chlamydia positive cases. Nucleic Acid Amplification Tests (NAATs) are the current gold standard for diagnosing CT/NG due to their high sensitivity and specificity. As such ??there is great need for an effective POC diagnostic test for CT/NG. In Aim 1 ?we will integrate assay controls and optimize our multiplex assay for CT/NG. In Aim 2, we will develop the “Beta” Novel Dx device that will meet the FDA and CLIA waiver guidance requirements. In Aim3, ?we will conduct more in-depth analytical studies for sensitivity, inclusivity, exclusivity, cross-reactivity of our optimized sample to answer assay. In Aim 4, we will place the Novel Dx system in clinical settings and conduct end-user performance and usability evaluations. The outcome of Phase II will provide sufficient data as well as a refined system design to inform a decision regarding multicenter clinical trials and product launch.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE STATEMENT Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are easily cured with antibiotics, however since most cases are asymptomatic, they often go undiagnosed and untreated. Untreated infections lead to serious sequelae including pelvic inflammatory disease (PID) and its associated complications, such as ectopic pregnancy, infertility, and chronic pelvic pain. Timely diagnosis using accurate point-of-care diagnostics and early treatment is necessary. We propose to develop a rapid, automated, multiplex nucleic acid amplification test for CT/NG to enable immediate testing and treatment of infected individuals in a single visit.

Project Terms:
Address; Antibiotic Resistance; Antibiotics; assay development; Automation; base; Bedside Testings; Biological Assay; Buffers; Cells; Chlamydia; Chlamydia trachomatis; chronic pelvic pain; Clinical; Clinical Sensitivity; Clinical Treatment; Clinical Trials; cost; cross reactivity; Data; design; Development; Device or Instrument Development; Devices; Diagnosis; diagnosis standard; Diagnostic; Diagnostic tests; Early treatment; Ectopic Pregnancy; Ensure; Europium; Evaluation; Failure; FDA approved; Female; follow-up; Formulation; Freeze Drying; Gold; Gonorrhea; hospital laboratories; Immunoassay; Individual; Infection; Infertility; instrument; Lateral; Lead; male; meetings; microdevice; Microfluidics; molecular diagnostics; Multi-Institutional Clinical Trial; multiplex detection; Neisseria gonorrhoeae; novel; Nucleic Acid Amplification Tests; Nucleic Acids; Organism; Outcome; particle; Patients; Pelvic Inflammatory Disease; Performance; Phase; Plasmids; point of care; point-of-care diagnostics; Preparation; programs; prospective; public health relevance; Reporter; Reporting; Reproducibility; research clinical testing; Running; Sampling; Sensitivity and Specificity; Sexually Transmitted Diseases; Small Business Innovation Research Grant; success; Swab; System; Technology; Testing; Time; Urine; usability; Vagina; Validation; validation studies; Visit; waiver