Michael P. McRae

Application of programmable bio-nano-chip system for the quantitative detection of drugs of abuse in oral fluids

OBJECTIVE There is currently a gap in on-site drug of abuse monitoring. Current detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. While remote laboratories then may provide confirmation and quantitative assessment of a presumptive positive, this instrumentation is expensive and decoupled from the initial sampling making the current drug-screening program inefficient and costly. The authors applied a noninvasive oral fluid sampling approach integrated with the in-development chip-based Programmable bio-nano-chip (p-BNC) platform for the detection of drugs of abuse. METHOD The p-BNC assay methodology was applied for the detection of tetrahydrocannabinol, morphine, amphetamine, methamphetamine, cocaine, methadone and benzodiazepines, initially using spiked buffered samples and, ultimately, using oral fluid specimen collected from consented volunteers. RESULTS Rapid (∼10min), sensitive detection (∼ng/mL) and quantitation of 12 drugs of abuse was demonstrated on the p-BNC platform. Furthermore, the system provided visibility to time-course of select drug and metabolite profiles in oral fluids; for the drug cocaine, three regions of slope were observed that, when combined with concentration measurements from this and prior impairment studies, information about cocaine-induced impairment may be revealed. CONCLUSIONS This chip-based p-BNC detection modality has significant potential to be used in the future by law enforcement officers for roadside drug testing and to serve a variety of other settings, including outpatient and inpatient drug rehabilitation centers, emergency rooms, prisons, schools, and in the workplace.

Next Generation Programmable Bio-Nano-Chip System for On-Site Quantitative Drug Detection in Oral Fluids

Current on-site drug of abuse detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. Test confirmation and quantitative assessment of a presumptive positive are then provided by remote laboratories, an inefficient and costly process decoupled from the initial sampling. Recently, a new noninvasive oral fluid sampling approach that is integrated with the chip-based Programmable Bio-Nano-Chip (p-BNC) platform has been developed for the rapid (~ 10 minutes), sensitive detection (~ ng/ml) and quantitation of 12 drugs of abuse. Furthermore, the system can provide the time-course of select drug and metabolite profiles in oral fluids. For cocaine, we observed three slope components were correlated with cocaine-induced impairment using this chipbased p-BNC detection modality. Thus, this p-BNC has significant potential for roadside drug testing by law enforcement officers. Initial work reported on chipbased drug detection was completed using ‘macro’ or “chip in the lab” prototypes, that included metal encased “flow cells”, external peristaltic pumps and a bench-top analyzer system instrumentation. We now describe the next generation miniaturized analyzer instrumentation along with customized disposables and sampling devices. These tools will offer real-time oral fluid drug monitoring capabilities, to be used for roadside drug testing as well as testing in clinical settings as a non-invasive, quantitative, accurate and sensitive tool to verify patient adherence to treatment.

Programmable Bio-Nano-Chip System: A Flexible Diagnostic Platform that Learns

Over the past few decades, the use of biomarkers has become increasingly intrinsic to the practice of medicine and clinical decisionmaking. Clinically validated biomarkers-whether nucleic acid, protein, or metabolite—provide health care providers and clinicians a means to quickly and objectively measure, track, and diagnose a patient’s past and present physiological state for a wide range of conditions. As a result, biomarkers help patients receive appropriate care, which in turn helps reduce healthcare costs [1,2]. Biomarker-based tests are typically developed by diagnostic companies, and are often purchased and performed by medical testing companies. Biomarkers also aid pharmaceutical companies in quickly and efficiently screening their candidate drug products for dosing, pharmacokinetics, safety, and efficacy, thus simultaneously speeding up development and lowering the costs of drug. Upstream in the R&D continuum, early-stage researchers look for biomarkers to help better understand disease etiologies.

Innovative Programmable Bio-Nano-Chip Digitizes Biology Using Sensors That Learn Bridging Biomarker Discovery and Clinical Implementation

The lack of standard tools and methodologies and the absence of a streamlined multimarker approval process have hindered the translation rate of new biomarkers into clinical practice for a variety of diseases afflicting humankind. Advanced novel technologies with superior analytical performance and reduced reagent costs, like the programmable bio-nano-chip system featured in this article, have potential to change the delivery of healthcare. This universal platform system has the capacity to digitize biology, resulting in a sensor modality with a capacity to learn. With well-planned device design, development, and distribution plans, there is an opportunity to translate benchtop discoveries in the genomics, proteomics, metabolomics, and glycomics fields by transforming the information content of key biomarkers into actionable signatures that can empower physicians and patients for a better management of healthcare. While the process is complicated and will take some time, showcased here are three application areas for this flexible platform that combines biomarker content with minimally invasive or non-invasive sampling, such as brush biopsy for oral cancer risk assessment; serum, plasma, and small volumes of blood for the assessment of cardiac risk and wellness; and oral fluid sampling for drugs of abuse testing at the point of need.

Challenges and opportunities for translating medical microdevices: insights from the programmable bio-nano-chip.

This perspective highlights the major challenges for the bioanalytical community, in particular the area of lab-on-a-chip sensors, as they relate to point-of-care diagnostics. There is a strong need for general-purpose and universal biosensing platforms that can perform multiplexed and multiclass assays on real-world clinical samples. However, the adoption of novel lab-on-a-chip/microfluidic devices has been slow as several key challenges remain for the translation of these new devices to clinical practice. A pipeline of promising medical microdevice technologies will be made possible by addressing the challenges of integration, failure to compete with cost and performance of existing technologies, requisite for new content, and regulatory approval and clinical adoption.

Programmable bio-nano-chip system for saliva diagnostics

This manuscript describes programmable Bio-Nano-Chip (p-BNC) approach that serves as miniaturized assay platform designed for the rapid detection and quantitation of multiple analytes in biological fluids along with the specific applications in salivary diagnostics intended for the point of need (PON). Included here are oral fluid-based tests for local periodontal disease, systemic cardiac disease and multiplexed tests for drugs of abuse.

Prediction of heart rate response to conclusion of the spontaneous breathing trial by fluctuation dissipation theory

The non-equilibrium fluctuation dissipation theorem is applied to predict how critically ill patients respond to treatment, based upon data currently collected by standard hospital monitoring devices. This framework is demonstrated on a common procedure in critical care: the spontaneous breathing trial. It is shown that the responses of groups of similar patients to the spontaneous breathing trial can be predicted by the non-equilibrium fluctuation dissipation approach. This mathematical framework, when fully formed and applied to other clinical interventions, may serve as part of the basis for personalized critical care.