SBIR-STTR Award

The United States is in the midst of a prescription opioid epidemic. Deaths from misuse (51 daily) exceed deaths from heroin overdose and account for nearly one-fifth of all drug-related deaths. The estimated burden on the US healthcare system was $9.5 billion in 2005 and increased to an estimated $72.5 billion annually in 2014. A key recommendation of several federal agencies is to use urine drug testing (UDT) before prescribing opioids to establish overdosing (above expected levels of opioids in urine) or misuse with intent to resell (low or absent opioids despite patient claims to the contrary). Current strategy for UDT involves a qualitative screening immunoassay, followed by quantification using HPLC or GC/MS for positive cases. Screening immunoassays use benchtop analyzers that require experienced personnel, time, and a laboratory setup. Physicians who do not have access to in-house testing have to send out patient samples for screening. Thus, laboratory testing of every patient suffering from chronic pain at every visit imposes unacceptable delays to treatment and is not followed by most physicians. A quick, affordable, layman operable, point of care UDT in the physician's office will help in rapid diagnosis of problems and potentially halt the epidemic. BreviTest Technologies has developed a low-cost, portable analyzer to perform a rapid, quantitative ELISA test within a 10-minute run time. The sample is loaded into a cartridge that is placed in the analyzer, and a robotic mechanism controls the movement of antibody-conjugated magnetic nanoparticles through successive fluid wells, where enhanced mixing patterns substantially reduce the time required for each ELISA step. This innovative approach enables the implementation of a rapid, portable, fully automated ELISA test with accuracy comparable to a standard laboratory ELISA. In this SBIR Phase I project, BreviTest will develop and optimize an ELISA test for opioids in urine using the BreviTest robotic analyzer. The Specific Aims for the project are: (1) Develop a competitive ELISA for opioids using the BreviTest analyzer platform. We will determine the optimal reagent concentrations for the immunoassay and characterize performance of the assay in the BreviTest platform. Performance parameters will include dynamic range, repeatability, and limit of quantification. (2) Perform a limited proof-of- concept field study of the analyzer on de-identified urine samples in collaboration with a local pathology laboratory. BreviTest offers a unique platform to create an ELISA test for performing rapid quantifications of urine drug levels at the physician's office, which will be an invaluable tool to render more effective dosing to patients, paving the way towards lower toxicity and a better quality of life.

Public Health Relevance Statement:
PROJECT NARRATIVE. Deaths from prescription opioids account for nearly one-fifth of all drug-related deaths in the US (51 deaths daily), through overdosing and misuse. Federal health agencies, aware of this growing epidemic, have advocated frequent urinary drug testing prior to prescriptions; however, physician compliance is poor because of the additional wait period for laboratory results. In this SBIR Phase I project, BreviTest Technologies proposes to develop, optimize, and conduct proof-of-concept studies for an affordable and quick urinary opioid assay that can be used by physicians in their offices for objective, accurate assessments prior to prescribing opioids.

Project Terms:
Advocate; Air; Analgesics; Antibodies; antibody conjugate; assay development; base; Biological Assay; Buffers; Centers for Disease Control and Prevention (U.S.); Cessation of life; chronic pain; Clinical; Collaborations; combat; cost; design; Detection; Devices; Diagnosis; Dose; drug testing; Economics; Enzyme-Linked Immunosorbent Assay; Epidemic; experience; Face; field study; Health; Healthcare Systems; heroin overdose; High Pressure Liquid Chromatography; Housing; Human Resources; Immunoassay; Individual; innovation; Laboratories; Legal patent; liquid chromatography mass spectrometry; Liquid substance; Magnetic nanoparticles; Mass Fragmentography; Movement; Narcotics; operation; Opiates; Opioid; opioid abuse; opioid use; Outpatients; Overdose; Pain; Pain management; Pathology; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Physicians; Physicians' Offices; point of care; prescription drug abuse; prescription opioid; prescription opioid misuse; Process; programs; Quality of life; rapid diagnosis; Reagent; Recommendation; response; Risk; Robotics; Running; Sampling; screening; Small Business Innovation Research Grant; Statistical Data Interpretation; System; Techniques; Technology; Testing; Time; tool; Toxic effect; Tracer; United States; urinary; Urine; Variant; Visit

BreviTest Technologies, LLC, proposes to develop a low-cost, point-of-care (POC) urine drug testing (UDT) device to detect opioids. The goal is for the assay platform to deliver quantitative performance similar to a standard laboratory ELISA. Phase I research and development showed the repeatability and accuracy of BreviTest’s proprietary assay technology. Current drug-screening immunoassays use benchtop analyzers that require experienced personnel, time, and a laboratory setup. Physicians without access to in-house testing have to send out patient samples for screening, resulting in unacceptable delays in the treatment of patients who are potentially suffering from chronic pain. Thus most physicians do not follow the federal recommendations to use urine drug testing (UDT) before prescribing opioids to identify potential opioid abuse, either from overdosing (above expected levels of opioids in urine) or intent to resell (low or absent opioids despite patient claims to the contrary). BreviTest Technologies has developed a low-cost, layman operable, POC analyzer to perform a quantitative ELISA test within a 10-minute run time. The sample is loaded into a cartridge that is placed in the analyzer and an automated mechanism controls the movement of antibody-conjugated magnetic microparticles through successive fluid wells with enhanced mixing patterns. This innovative approach enables the implementation of a rapid, portable, fully automated ELISA test with accuracy comparable to a standard laboratory ELISA. The Specific Aims for this Phase II project are: (1) Finalize development and implementation of repeatability and calibration protocols according to industry standards for the diagnostic device and disposable test cartridges; (2) Build and characterize fully integrated prototypes to obtain a finalized device design, packaging, process, and tooling; (3) Perform testing of finalized BreviTest device and performance validation using patient urine samples. The expected outcome of this project will be a device designed for manufacturing (DFM), built and characterized by a contract manufacturer, validated in a pilot study and user simulation, ready to enter design controls, and with a regulatory and commercialization path in place. BreviTest offers a unique platform to create an ELISA test for performing rapid quantifications of urine drug levels in a physician’s office, providing an invaluable tool to render more effective pain management dosing to patients, thus paving the way towards lower toxicity and a better quality of life.

Public Health Relevance Statement:
PROJECT NARRATIVE. Deaths from prescription opioids account for nearly one-fifth of all drug-related deaths in the US (134 deaths daily), through overdosing and misuse. Federal health agencies, aware of this growing epidemic, have advocated urinary drug testing prior to prescriptions; however, physician compliance is poor because of the additional wait period for laboratory results. The proposed point-of-care diagnostic device will fill a critical unmet need for an affordable and quick urinary opioid test that can be used by physicians in their offices for objective, accurate assessments prior to prescribing opioids. The technology can potentially be used in pain clinics, private practice, public health laboratories, and urban emergency departments throughout the United States.

NIH Spending Category:
Bioengineering; Chronic Pain; Drug Abuse (NIDA only); Nanotechnology; Opioid Misuse and Addiction; Opioids; Pain Research; Prescription Drug Abuse; Substance Abuse

Project Terms:
Accident and Emergency department; Advocate; Air; Analgesics; antibody conjugate; Awareness; base; Biological Assay; Calibration; Centers for Disease Control and Prevention (U.S.); Cessation of life; chronic pain; Clinical; commercialization; Contracts; cost; cross reactivity; design; Development; Device Designs; Devices; Diagnostic; Dimensions; Dose; Drug Screening; drug testing; Economics; Environment; Enzyme-Linked Immunosorbent Assay; Epidemic; Evaluation; experience; Face; Freezing; Goals; Health; Healthcare Systems; High Pressure Liquid Chromatography; Human Resources; Immunoassay; Individual; Industry Standard; innovation; Institutional Review Boards; Laboratories; Legal patent; Life; Liquid substance; Magnetic nanoparticles; Magnetism; Manufacturer Name; manufacturing scale-up; Mass Fragmentography; Methods; misuse of prescription only drugs; Movement; Narcotics; off-patent; Opioid; opioid abuse; Opioid Analgesics; opioid overdose; Outcome; Outpatients; Overdose; Pain; Pain Clinics; Pain management; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Physicians; Physicians' Offices; Pilot Projects; point of care; point-of-care diagnostics; portability; prescription drug abuse; prescription opioid; prescription opioid misuse; prescription pain reliever; Private Practice; Process; Protocols documentation; prototype; Public Health; Quality of life; Reagent; Recommendation; research and development; research clinical testing; response; Risk; Running; Sampling; screening; Screening Result; Secure; Shipping; simulation; Site; Small Business Innovation Research Grant; Sterility; Technology; Testing; Time; tool; Toxic effect; trial design; United States; urinary; Urine; Validation; validation studies; waiver