Description:
OBJECTIVE: Develop advanced technologies that can be self-operated by a patient or a minimally trained operator to collect large volumes/weights of a biospecimen for clinical use, such as diagnostic and remote clinical trials, or for research applications such as biomarker discovery/validation. The majority of diagnostic tests and research assays require blood biospecimens that are traditionally collected using phlebotomy techniques performed by trained personnel. In limited resource areas, such as DoD deployment locations, remote or impoverished geographic areas, or emergency response locations, absence of blood sample collection by a trained phlebotomist can be a significant limitation to clinical care. Lancet or finger stick blood collection methods are one solution to minimize the need for these resources but suffer from low biofluid volumes that statistically may not contain the biomarker(s) of interest at the concentrations necessary for detection or clinical correlation. See reference #1 for examples of proteins in blood. Solutions are sought that enable the simple self-collection of sufficient biospecimen volumes or weights for the detection of low abundance diagnostic biomarkers. All biospecimens are of interest and include blood, sweat, tears, etc. Technologies developed should be minimally invasive, simple to operate, and allow for remote self-collection of a sufficient sample volume (e.g.>100 microliters for blood) or weight, to allow for detection of a low-abundance panel of biomarkers at a reference laboratory or point-of-care setting. Potential users include minimally trained individuals and medics in settings where phlebotomy is not available. If the technology is successfully developed, the capability to statistically capture low abundance biomarkers by increasing the amount of biospecimen collected in low resourced settings is anticipated to widely improve clinical care and biomedical research by enabling remote clinical trials, distributed remote access diagnostics, public health surveillance and biomarker research. DESCRIPTION: There is the need for technologies capable of collecting patient biospecimens at sufficient volumes or weights, in a manner that allows for statistically relevant clinical guidance after the sample has been processed and analyzed. At the same time, enabling the capability to self-collect a biospecimen could provide a means to more confidently diagnose or track disease at its earliest stages, provide an ability to better expand clinical trials into remote settings, and increase the diversity of population cohorts needed for biomarker research. For example, blood biospecimens are the biofluid of choice for most diagnostic applications but require trained phlebotomists to collect and process. Simultaneously, there has been a push towards the miniaturization of detection technologies (eg."lab-on-a-chip"and"nano-bio"technologies), but there has been a disconnect between sample acquisition and downstream analysis in a manner that allows for the detection of low abundance analytes. Aggressive low volume scaling through finger-stick or lancet components affords clear advantages for sample preparation, reagent usage, thermal load, manipulation, and reaction kinetics, but there is nevertheless the challenge of dealing with"the law of small numbers", or Poisson"s Distribution, which indicates that for small biospecimen volumes there may be no targets available for amplification or detection. In other words, diagnostic instruments may be developed that are small, portable, and require only a few drops of blood, but if the target analyte is not present in the small volume, the test could be susceptible to false negatives or not provide sufficient statistical confidence to provide clinical guidance. Additionally, biospecimens other than blood, such as sweat, interstitial fluids, or tears may have the potential to be a powerful natural repository of clinically relevant biomarkers but there lack the technologies for self-collection and concentration. Technologies that offer the simplicity of a finger stick device (as an example) with the capability to collect larger biospecimen volumes or weights would overcome a diagnostic hurdle that limits widespread diagnostic testing outside of traditional clinical settings such as a clinic or hospital. Therefore, proposals are sought that address large volume (eg.>100 microlitersfor blood) or weight biospecimen collection via a device that is simple to operate and minimally invasive. The design should consider minimally trained individuals and medics as potential users. Proposers are encouraged to consider methods and technologies compatible with clinical workflows, good laboratory practices (GLP), and good manufacturing practice (GMP) procedures. PHASE I: Demonstrate feasibility of methods or technologies for large volume or weight collection. Proposers must address both the volume/weight of biospecimen collected, as well as address how device operation is conducted under conditions of minimal invasiveness and ease-of-use. Proposers should aim to collect as large a volume or weight as possible (eg. at least 100 microliters for blood) while retaining the capability for operation by a minimally trained user. Collection devices may be designed to hold the collected biospecimen within the device or to dispense the biospecimen into an instrument or alternate storage device. Proposers should demonstrate initial designs and collection volumes/weights, and project Phase II collection volume/weight capabilities. Proposals that demonstrate universal compatibility for downstream analysis under a wide dynamic range of analytes are preferred. Of interest are quantitative metrics measured with a variety of protein, nucleic acid, metabolic and/or other analytes relevant to human biology. Phase I efforts should justify the applicability to settings such as home use, and consideration of FDA regulations is encouraged. PHASE II: Phase II efforts should quantify collected biospecimen volume/weight and address reproducibility of the collection volume/weight with different prototypes under similar and different conditions. Detection of a panel of well-characterized, low abundance biomarkers should be demonstrated from collected samples using standard laboratory practices. Of interest are quantitative metrics measured with a variety of protein, nucleic acid, metabolite and/or other analytes relevant to human biology. Phase II efforts should evaluate the device effectiveness and reproducibility when operated by untrained users. Additional interests include demonstrations that the proposed technology is developed to include standardization/normalization of the biospecimen to reference analyte concentrations across collections, with sensitivities that can address sample variability. Manufacturing designs and costs should be considered for all components of the device. Compatibility of the collection device with downstream biospecimen storage devices and/or analysis technologies should be considered. Device potential for FDA clearance as a blood collection device for home use or physician office settings should be described. PHASE III: The technology to be developed should enable blood collection outside of a major clinical facility and therefore could have significant impact on the clinical diagnostic market. There is a significant commercial market for medical diagnostics and home-use physician-office based diagnostic testing is a growing element of this market. The developed technology would potentially allow collection of sufficient sample in such settings, as well as enable clinically valid diagnostic testing and biomarker research. Potential commercial partnerships/customers include major diagnostics companies and life sciences research technology companies. The technology to be developed is critical for DoD, as many medics have minimal training. Development of a FDA-approved collection device could enable use of newly developed diagnostic tests in remote/deployment settings as well as expand the military capabilities to perform more effective clinical trials of new therapeutics and diagnostics in remote settings or expand capabilities to detect and track emerging disease. Potential transition customers include Center for Disease Control and Prevention, Air Force Surgeon General, Military Health System - Defense Medical Research and Development Program (MHS DMRDP), Military Infectious Diseases Research Program (MIDRP), and the commercial sector.
