Marijuana (e.g., cannabis) is the most frequently detected drug of abuse. Cannabis abuse has a substantial impact on public safety as driving under the influence of cannabis will impair driving skill and the marijuana use in the workplace will increase the risk of adverse events and the loss of productivity. With the recent wave of legalization of marijuana use in numerous states and the increase of use marijuana in re-creation and medical treatment, the US is experiencing a rise in cases of driving under influence of cannabis and workplace cannabis intoxication. The lack of sensitive, rapid, easy-to-use and reliable tool for on-site cannabinoid tests is a critical gap in the ability of Law enforcement officials, workplace drug testing programs, and researchers in the field of drug abuse to measure present cannabis intoxication. The current established cannabis testing methods are either laboratory enzyme-linked immunosorbent assay (ELISA) or GC/MS for the detection of the cannabis metabolites in urine or blood which take 1 to 3 hours and require a laboratory setting; however, the logistics of obtaining urine or blood samples on site represents a major limitation of current methods. We propose to develop a low-cost, disposable, point-of-use, highly sensitive and specific non- instrument test strip that enables the convenient onsite detection of the cannabis intoxication in saliva. The test requires no special training to operate and qualitative yes/no and semi-quantitative results are visibly obtained within ten minutes. To circumvent the technical challenge of a lateral flow assay (LFA) strips ability to measure low concentration of cannabis in saliva fluid (e.g., sensitivity meets the cutoff concentration 5 ng/mL of marijuana intoxication), we will implement innovative strip architecture and built- in signal amplification by dual-labeled Au nanoparticle conjugates into the strip to enhance the sensitivity. To increase the specificity for cannabis detection, we propose a new assay format by using peptide specific against the immunocomplex of cannabis-capture antibody in the test line of the LFA. We will optimize reagent concentrations and LFA parameters along with statistical validation of dynamic range, specificity, and sensitivity in Phase I project. The completion of these proof-of-concept studies will demonstrate the ability of this new type LFA to measure cannabis concentration in saliva samples, at concentrations relevant to roadside and workplace intoxication analysis. In Phase II, we will: 1) optimize the LFAs configuration to reduce false negatives and false positives to ensure reliable detection, 2) design and develop any associated devices (cassette, packaging and labeling), 3) develop smartphone based quantitative analysis of the LFA test results and data processing Apps recording and wireless communication of test results, and 4) develop manufacturing processes for pilot scale production of 2000 LFAs and validate the cannabis saliva test with a large cohort of saliva samples (> 250 clinical saliva samples). At the end of Phase II, the colorimetric LFAs will be ready for transferring to full-scale automated manufacturing, and final LFAs device will be produced at large scale for clinical validation towards a defined 510(k) clearance by the FDA.
Public Health Relevance Statement: Project Narrative Marijuana (e.g. cannabis) is the most frequently used illicit drug of abuse in the United States, and abuse of cannabis also has a substantial impact on public safety. With the recent wave of legalization of marijuana use in numerous states, the US is experiencing a rise in cases of driving under influence of cannabis and workplace cannabis intoxication. There is a critical need for a rapid, onsite cannabis intoxication test for highway law enforcement and workplace drug testing programs. If funded, this proposed project will fill current technology void in developing a low-cost, point-of-use, highly sensitive and specific non-instrument test that enables the convenient onsite detection of the cannabis (marijuana) intoxication.
Project Terms: Address; Adverse event; Antibodies; Architecture; base; Benchmarking; Biological Assay; Blood; Blood specimen; Cannabinoids; Cannabis; Cannabis Abuse; Cellular Phone; Clinic; Clinical; cohort; commercialization; Communication; Complex; computerized data processing; cost; Data; design; Detection; Development; Devices; driving under influence; Drug abuse; Drug Addiction; drug of abuse; drug testing; Ensure; Enzyme-Linked Immunosorbent Assay; experience; Funding; Geographic state; Hour; illicit drug use; Immunoglobulin G; impaired driving performance; Individual; innovation; instrument; Intoxication; Label; Laboratories; Lateral; lateral line; Law Enforcement; Legal; Libraries; Liquid substance; Logistics; manufacturing process; Marijuana; marijuana use; marijuana user; Mass Fragmentography; Measures; Medical; Medical Marijuana; meetings; Methods; Motor Vehicles; nanoparticle; novel; operation; Patients; Peptides; Performance; Pharmaceutical Preparations; Phase; Preparation; Production; productivity loss; programs; Proteins; prototype; Reagent; Research Personnel; Risk; Safety; Saliva; Sampling; Self Administration; Sensitivity and Specificity; Signal Transduction; Site; skills; Specificity; Technology; Test Result; Testing; Tetrahydrocannabinol; tool; Training; United States; Urine; Validation; Visual; waiver; Wireless Technology; Work; Workplace
