Request for Position Statements
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) announces the creation of the Advanced Research Program (ARP). This program is designed to promote new high-risk approaches to traditionally intractable alcohol-related problems, the solution of which may result in major scientific breakthroughs. The NIAAA provides national leadership to the alcohol research community and funds approximately 90 percent of all alcohol research conducted in the U.S.
The ARP is interested in the development of an alcohol biosensor that is capable of continuous measuring of alcohol levels. Such a device is of great research interest and is of obvious commercial interest. Critical features and possible specifications are described below.
Integrated Alcohol Sensing and Data Analysis System
The proposed research program is aimed at the development of an innovative alcohol biosensor providing a revolutionary advance in the ability to obtain valid and reliable dynamic information on the circumstances related to an individual’s consumption of alcohol in daily life. A key innovative concept to be applied is the fully integrated sensing and processing of the resulting data, an approach offering the potential to succeed where others have fallen short. The anticipated result of this program is the capability to gather and analyze data at the required resolution and finesse for a great variety of experimental and analytic studies of alcohol-related phenomena, such as sensitization, acute tolerance, chronic tolerance, dependence, withdrawal, craving and relapse. Fundamental information on the time-varying distribution of alcohol throughout various organs may also prove useful in studies of the disposition and elimination of alcohol in the body. The capabilities envisioned may enable exciting applications such as the evaluation of clinical interventions and the development of relapse prevention programs.
Current Technologies and Examples of Deficiencies
Existing approaches to alcohol measurement have attending deficiencies.
Self-reports: questionable validity; inadequate chronology; statistical issues associated with self-selection of samples Breath sensors: disruption of ongoing activity required for measurement; time requirement to obtain adequate breath sample Wrist sensor: Irritation; latency of measurement; back diffusion of alcohol; easily removable Transdermal sensor: quantification, spatial and temporal resolution inadequate; easily removable; calibration issues associated with placement of device.
Fundamental Requirements of Envisioned Developments
Success in this program is expected to require tightly integrated teams comprising diverse technical backgrounds within alcohol research, physics, engineering, and the mathematical sciences. The program will begin by enlisting the aid of this multi-disciplinary community to help determine appropriate end-user applications and the necessary system level specifications and developments. At present, the initial estimate of required capabilities includes but is not limited to the following features:
Development of integrated sensing modalities, spatial/temporal pattern analysis, and data reduction/compression technologies enabling determination of alcohol concentration every 1 to 5 minutes, with spatial resolution sufficient to study concentration variation between different organ systems and regions of the body, and with concentration resolution of (5 mg/dl) within a range of (5 –500 mg/dl). Measurement fidelity should be robust to subject’s activities up to and including active efforts at tampering. System should provide for storage and/or telemetric exfiltration of data (without removal of the sensor). System should provide power and data storage capabilities for at least one month of continuous activity. Sensor system should have no deleterious effects on subject’s comfort, health, and safety.
Additional desirable features may include the ability to monitor alcohol levels in different body organs and systems simultaneously; a capability to provide other physiologic measurements such as heart rate, blood pressure, temperature, galvanic skin impedance, and blood chemistry measurements, including glucose, enzymes, and hormone levels; ability to sense and record information about the individual’s location and activity; and ability to report data telemetrically.
Envisioned Technology Developments and Innovative Concepts
Radical new approaches are required to obtain joint measurement and analysis of specific high-resolution vital data through tissue. Challenges include getting high-fidelity measured data out of tissue, particularly if spatial localization is to be included and multiple physiologic effects are to be monitored. This is difficult because tissue is a dispersive and scattering medium, which often foils simple methods of moving high- resolution, detailed spatiotemporal information in and out of the body.
A successful program will require end-to-end design of the biosensor system and must include consideration of the various applications and end uses for outputs of the system. This will include an understanding of the experiments that will likely be conducted using the sensor, possible interventions or probing of the subject during data collection, and attendant requirements of data reduction and analysis and pattern discovery.
Developments will not be confined to construction of a simple physical sensor device, but rather instantiation of a methodology for the design of integrated sensing, processing, and analysis. The resulting biosensor system is intended to enable the elucidation of useful information patterns, as opposed to merely providing new means for producing enormous stores of unreduced data.
There are several promising approaches towards the desired capabilities. To explore and refine these, we will begin the program by bringing together a diverse community of life scientists, technologists, and mathematicians in order to facilitate a systems level consideration of the problem and allow the program to harvest the results of this interaction. Preliminary discussions have provided examples of potential approaches.
One example concerns the basic concept of multispectral source coding, which seeks to actively encode relevant information inside the tissue in a fashion that enhances and simplifies the problem of getting accurate high-fidelity information out of the body.
Two basic avenues for this are presently under consideration.
A completely non-invasive approach involving infrared spectroscopic imaging through tissue; Application of tags/markers/implants with radio frequency or optical readout of measurements through tissue.
In the former case, recent advances in active interferometric imaging provide a unique capability to integrate light signals from specific domains of multidimensional space. With this technology, one envisions external sensors that use holographic coding to isolate light signals from specific layers, regions or types of tissue, that use Doppler analysis to integrate on signals from flowing blood, and that filter on vasculature or bone structure, or that image on specific spectral structures and biochemical species.
In the latter case, one may consider the application of recent advances in microscale or nanoscale electronics, possibly using electro and photoactive polymeric engineered devices in the detection, readout, and power supply roles for biocompatibility. Another approach would use engineered bioluminescence reported, with appropriate encapsulation methods for biocompatibility.
In either approach, one would utilize periodic telemetric data dumps to a small base station, possibly installed in the subject’s house. There is the possibility of applying miniaturized GPS receivers in association with the sensors to provide information on subject location and movement.
Anticipated Impact
Research pertaining to the prevention and treatment of alcoholism requires detailed information on drinking patterns over extended periods. Previous methods of obtaining such data have provided more or less indirect evaluations of alcohol content by a variety of methods including breath tests, self-reporting surveys, and wrist-worn alcohol-diffusion measurement devices. All have proven deficient in several key regards.
The proposed program contemplates a root-level approach to the required data collection by providing for direct measurement, monitoring, recording, and reporting of alcohol concentration data. This will provide for continuous measurements over extended periods and provide data that are detailed and reliably accurate. The measurement process will have minimal impact on the subject and be immune to accidental or intentional disruption or discontinuation of the measurement functions. It may be possible to include the ability to monitor alcohol levels in different body organs and systems simultaneously; a capability to provide other physiologic measurements such as blood pressure, temperature, and other blood chemistry measurements including glucose, enzyme and hormone levels; ability to sense and record information about the individual’s location and activity; and ability to report data telemetrically.
The program will go far beyond the development of a particular physical sensing device, and will in fact create an integrated sensing, processing, and analysis design methodology. This will be demonstrated by providing a systems level solution to the needs of various end-users, with the ultimate goal of providing them with the information most useful to their purposes.
NIAAA invites members of the academic, government, and industrial research communities to provide input that will contribute to defining the general scope of a Broad Agency Announcement request for contracts in the summer/fall of 2001. Input is encouraged in the form of position statements, but will also be accepted in alternative informal written formats. Interested parties are encouraged to provide information on new areas of technological opportunity that could speed progress towards the scientific goals stated above. We are interested in technologies that could provide an integrated technology platform or components that could contribute to the final platform.
NIAAA is looking for opportunities that will yield entirely new technological approaches or quantum improvements in existing technologies. We are looking for ideas that project innovation beyond the range of research traditionally supported through the NIH investigator-initiated research support process.
The participation of investigators from varied disciplines will be required for the development of system components and an integrated strategy for sensing, measuring, and signaling. The NIAAA welcomes the submission of ideas from investigators in all disciplines, including but not limited to bioengineering, chemistry, physics, mathematics, pharmacology, and biology.
Position statements should broadly address the following:
· What is the nature of the technological opportunity?
· What are the current capabilities of the technology?
· What technological barriers would need to be overcome to meet the define goal?
· How would the technological opportunity contribute to the goal of a common technology
platform for the measurement of alcohol concentration as well as for other physiological
variables?
· What would be the potential impact of the technology on approaches to the early
detection, diagnosis, and treatment of alcohol-related disorders?
Position statements should address areas of technology, not individual research projects. DO NOT INCLUDE PROPRIETARY INFORMATION. Text should be limited to two pages or less. Position statements should be clearly labeled with a cover sheet indicating POSITION STATEMENT and contact information for the author(s). To allow time for consideration of all position statements and comments, it is requested that position statements and comments be submitted on or before 2 May 2001. Position statements, comments, and requests for further information should be addressed to:
Dennis M. Healy, Jr., Ph.D.
Office of Scientific Affairs
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Blvd., Suite 409
Bethesda, MD 20892-7003
Phone: (301) 405-0270
Fax: (301) 443-6077
E-mail: dhealy@willco.niaaa.nih.gov