SBIR-STTR Award

Opioid misuse and abuse is an epidemic of global concern to public health and safety, causing over 60,000 deaths annually in the United States. Obtaining real-time data on the misuse/abuse of opioids is a major challenge as this information is limited to population surveys and drug surveillance data. There is an urgency to develop smart city tools that will measure and monitor illicit drug metabolites to achieve crucial insight into the prevalence of opioid misuse/abuse without stigmatizing communities. Monitoring opioid metabolites in wastewater is a proven strategy to identify areas needing intervention instead of relying on emergency-room statistics and overdose deaths. However, current wastewater drug analysis requires costly laboratory-based tests that involves labor intensive sample collection, transportation, and analysis, resulting in long (days) turnaround times. Giner proposes to develop a compact, label-free Graphene Field Effect Transistor (G-FET) sensor utilizing high-specificity aptamers for rapid, accurate, and cost-effective monitoring of illicit drugs and their metabolites in wastewater samples. Since it generates rapid results compared to incumbent methods which rely on batch sampling of wastewater streams, and expensive, time consuming analysis, this technology will provide actionable real time data at a fraction of the cost of incumbent methods, encouraging broad use. The goal of Phase I program is to demonstrate a proof-of-concept test for two major street heroine metabolites in wastewater at pg/mL levels: Morphine and Norfentanyl. Multiple samples from wastewater treatment plants will be analyzed with Giner's assay and results will be cross-validated using the gold standard HPLC-MS/MS method. The Specific Aims of the Phase I effort incide: 1) Development of a wastewater G-FET assay for Morphine and Norfentanyl; 2) Validation of sensor sensitivity and specificity; and 3) Sensor performance testing in real wastewater samples. Once developed, the technology will also be suitable for detection of any target illicit drug for which an aptamer can be prepared.

Public Health Relevance Statement:
PROJECT NARRATIVE Giner proposes to develop a compact, label-free sensor tool for rapid, accurate, and low-cost monitoring of illicit drugs in wastewater. Given the growing opioid epidemic, and fatalities associated with synthetics such as fentanyl, the proposed wastewater monitor technology has broad potential to provide near real- time information to address the public health and safety issues surrounding drug misuse and abuse. There are just over 100,000 publicly owned treatment works (POTW) in the world, and this technology could find use at innumerable locations within large metro districts.

Project Terms:
Algorithms; Back; Dorsum; Biological Assay; Assay; Bioassay; Biologic Assays; Boston; Buffers; High Pressure Liquid Chromatography; HPLC; High Performance Liquid Chromatography; High Speed Liquid Chromatography; Cities; Communities; Crime; Cessation of life; Death; Heroin; Diacetylmorphine; Diamorphine; District of Columbia; D.C. Washington; DC Washington; Drug abuse; abuse of drugs; abuses drugs; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Epidemic; Fentanyl; Actiq; Duragesic; Fentanest; Fentyl; Phentanyl; Goals; Gold; Health; Health Personnel; Health Care Providers; Healthcare Providers; Healthcare worker; health care personnel; health care worker; health provider; health workforce; healthcare personnel; medical personnel; treatment provider; Laboratories; Massachusetts; Methods; Morphine; Infumorph; Kadian; MS Contin; MSir; Morphia; Oramorph; Oramorph SR; Roxanol; Statex SR; Mouth Diseases; Oral Cavity Disease; Oral Cavity Disorder; Oral Disease; Oral Disorder; mouth disorder; Nucleic Acids; opioid abuse; opiate abuse; opiate drug abuse; opioid drug abuse; Overdose; Plants; Productivity; Public Health; research and development; Development and Research; R & D; R&D; Safety; Public Health Schools; Sensitivity and Specificity; Specificity; statistics; Stigmatization; Students; Technology; Testing; Time; Transistors; Transportation; United States; Universities; Work; Measures; S Phase; S Period; Synthesis Period; Synthesis Phase; Drug Monitoring; conference; convention; summit; symposia; symposium; Illicit Drugs; health care; Healthcare; Law Enforcement; Job Location; Job Place; Job Setting; Job Site; Work Location; Work Place; Work-Site; Worksite; work setting; Workplace; base; population survey; Label; sensor; specimen collection; sample collection; Area; Phase; insight; Individual; Opiates; Opioid; Measurement; drug use; Drug usage; non-invasive diagnosis; non-invasive diagnostic; noninvasive diagnostic; noninvasive diagnosis; septic; tool; PWUD; people who use drugs; people who use illicit drugs; persons who use drugs; Drug user; programs; Salivary; Stream; System; Location; Test Result; Best Practice Analysis; Benchmarking; collegiate; college; Emergency Department; Emergency room; Accident and Emergency department; early detection; Early Diagnosis; electrical property; experience; aptamer; professor; Municipalities; Devices; Epidemiologic Research; Epidemiologic Studies; Epidemiological Studies; Epidemiology Research; epidemiologic investigation; epidemiology study; Sampling; performance tests; cross reactivity; portability; Intervention Strategies; interventional strategy; Intervention; Address; Data; Detection; NIDA; National Institute on Drug Abuse; National Institute of Drug Abuse; Validation; Monitor; developmental; Development; cost; designing; design; cost effective; Prevalence; Consumption; overdose death; surveillance data; early biomarkers; early detection markers; early detection biomarkers; opiate consumption; opiate drug use; opiate intake; opiate use; opioid consumption; opioid drug use; opioid intake; opioid use; medication misuse; drug misuse; graphene; opiate crisis; opioid crisis; opioid epidemic; opiate overdose; opiate related overdose; opioid drug overdose; opioid induced overdose; opioid intoxication; opioid medication overdose; opioid poisoning; opioid related overdose; opioid toxicity; opioid overdose; non-medical opioid use; nonmedical opioid use; opiate misuse; opioid misuse

Opioid crisis (abuse and misuse) is an epidemic of global concern to public health and safety, causing over 70,000 deaths annually in the United States. Obtaining real-time data on the use of opioids is a major challenge as this information is limited to population surveys and drug surveillance data. There is an urgent public health need for monitoring tools to achieve crucial insight into the prevalence of opioid misuse/abuse without stigmatizing communities. Wastewater monitoring is a proven strategy to identify areas needing intervention instead of relying on emergency-room statistics and overdose deaths. However, current wastewater drug analysis requires costly laboratory-based tests that involves labor intensive sample collection, transportation, and analysis, resulting in long (days) turnaround times. Giner proposes to develop a compact, portable, label-free Graphene Field Effect Transistor (G-FET) sensor utilizing high-specificity aptamers for rapid, accurate, cost-effective, and multiplexing monitoring of opioid drug metabolites in wastewater samples. Since it generates rapid results compared to incumbent methods which rely on batch sampling of wastewater streams followed by expensive, time consuming analysis, this technology will provide actionable real time data at a fraction of the cost of incumbent methods, encouraging broad use. The goal of Phase II program is to demonstrate a field-ready prototype and a test methodology for simultaneous detection of multiple opioid metabolites in wastewater at pg/mL levels. During the Phase I work, Giner successfully detected three opioid metabolites in wastewater samples that are also associated with street heroin use: Norfentanyl (a metabolite of fentanyl, a synthetic opioid), EDDP (a metabolite of methadone, fully synthetic opioid), and Noroxycodone (a semisynthetic opioid, metabolite of oxycodone). We will also add Morphine (main heroine metabolite, a natural opioid) to our Phase II program. Multiple samples from wastewater treatment plants will be analyzed with Giner's sensor and results will be cross-validated using the gold standard HPLC-MS/MS method. Giner will achieve this by using its prior expertise in bio/sensors and wastewater testing and in close collaboration with an interdisciplinary team of scientists, engineers, and environmental wastewater epidemiologists. Once developed, the technology will also be suitable for detection of any target illicit drug for which an aptamer can be prepared.

Public Health Relevance Statement:
PROJECT NARRATIVE Giner proposes to develop a compact, portable sensor instrument for rapid, accurate, and low-cost monitoring of opioid metabolites in wastewater. Given the growing opioid epidemic, and fatalities associated with synthetics such as fentanyl, the proposed wastewater monitor technology has broad potential to provide crucial information to address the public health and safety issues surrounding drug misuse and abuse. Fully developed, this technology will provide actionable real-time data at a fraction of the cost of incumbent methods and could find use at innumerable wastewater collection sites within large metro districts.

Project Terms:
Algorithms; Award; Back; Dorsum; Biological Assay; Assay; Bioassay; Biologic Assays; Boston; High Pressure Liquid Chromatography; HPLC; High Performance Liquid Chromatography; High Speed Liquid Chromatography; Cities; Communities; Data Correlations; Crime; Cessation of life; Death; Heroin; Diacetylmorphine; Diamorphine; Drug abuse; abuse of drugs; abuses drugs; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Electronics; electronic device; Engineering; Epidemic; Fentanyl; Actiq; Duragesic; Fentanest; Fentyl; Phentanyl; Goals; Gold; Grant; instrumentation; Laboratories; Massachusetts; Methadone; Adanon; Althose; Dolophine; Methadose; Methods; Methodology; Morphine; Infumorph; Kadian; MS Contin; MSir; Morphia; Oramorph; Oramorph SR; Roxanol; Statex SR; New York; Nucleic Acids; opiate abuse; opiate drug abuse; opioid drug abuse; opioid abuse; Overdose; Dihydrohydroxycodeinone; Oxycodeinon; Oxycodone SR; Oxycontin; Roxicodone; Oxycodone; Plants; Productivity; Public Health; Development and Research; R & D; R&D; research and development; Safety; Specificity; statistics; Stigmatization; Technology; Testing; Time; Transistors; Transportation; United States; Universities; Work; Measures; Illicit Drugs; Healthcare; health care; Law Enforcement; Workplace; Job Location; Job Place; Job Setting; Job Site; Work Location; Work Place; Work-Site; Worksite; work setting; base; population survey; Label; sensor; sample collection; specimen collection; Site; Area; Phase; insight; Individual; Opiates; Opioid; Measurement; drug use; Drug usage; Collaborations; septic; tool; PWUD; people who use drugs; people who use illicit drugs; persons who use drugs; Drug user; instrument; programs; Environmental Medicine; Scientist; Stream; Pattern; System; Test Result; Best Practice Analysis; Benchmarking; interest; collegiate; college; Emergency Department; Emergency room; Accident and Emergency department; field based data; field learning; field test; field study; success; water quality; aptamer; cohort; tech development; technology development; Devices; Epidemiologic Research; Epidemiologic Studies; Epidemiological Studies; Epidemiology Research; epidemiologic investigation; epidemiology study; Sampling; portability; Intervention Strategies; interventional strategy; Intervention; µfluidic; Microfluidics; Address; Microfluidic Device; Microfluidic Lab-On-A-Chip; microfluidic chip; Microfluidic Microchips; Data; Detection; NIDA; National Institute on Drug Abuse; National Institute of Drug Abuse; Collection; Epidemiologist; Validation; Monitor; cost; design; designing; cost effective; Prevalence; Consumption; prototype; commercialization; overdose death; overdose fatalities; surveillance data; Secure; opioid use; opiate consumption; opiate drug use; opiate intake; opiate use; opioid consumption; opioid drug use; opioid intake; drug misuse; medication misuse; graphene; opioid epidemic; opiate crisis; opioid crisis; opioid overdose; opiate overdose; opiate related overdose; opioid drug overdose; opioid induced overdose; opioid intoxication; opioid medication overdose; opioid poisoning; opioid related overdose; opioid toxicity; sensor technology; sensing technology; heroin use; heroin intake; opioid misuse; non-medical opioid use; nonmedical opioid use; opiate misuse; synthetic opioid; synthetic opiate; wastewater testing; waste water based testing; waste water testing; wastewater based testing; wastewater monitoring; waste water based monitoring; waste water monitoring; wastewater based monitoring; wastewater epidemiology; waste water based epidemiology; waste water epidemiology; wastewater based epidemiology; wastewater samples; waste water sample; waste water samples; wastewater sample; wastewater sampling; waste water sampling; detection limit; mobile sensor; portable sensor; diagnostic strategy; diagnostic approach