Point of Care Technologies for the Evaluation and Management of Obstetrics, Neonatal, and Pediatric Critical Care Patients, and for Patients with Disorders of Reproductive Tract and Infertility (R43/R44)

Many medical conditions in obstetrics, neonatology, pediatric critical care, reproductive endocrinology and infertility involve clinical states that evolve or change over short time frames.  For example, critically ill neonatal and pediatric patients are particularly fragile needing careful monitoring of their diseases processes, fine-tuning of their care based on laboratory findings and changing clinical status, and timely interventions as conditions change. Most of these are carried out using a wide range of technological support including electronic devices, tests for assessing biochemical variables; imaging techniques; ancillary equipment such as those needed to adjust ventilator settings, intravenous medication pumps, or blood pressure monitoring systems. Modern technological innovations are the backbone for offering state-of-the art critical care support.  Yet, much of the equipment, instruments, and devices used in pediatric/neonatal practice are miniaturized versions of those used for older age group patients. Advances in critical care obstetrics have been limited because of difficulty in testing new instruments in pregnant women. Due to presumed difficulties in obtaining regulatory approvals, rarely are medical devices and instruments tested in the critical care obstetrics field. Thus, with a few exceptions, instruments and devices have not been developed with rigorous evaluations for efficacy and safety for use in pregnant patients, in neonates, and in children of all ages. This is an existential problem because pregnancy is a constantly changing physiological state, as are the neonatal and pediatric periods. Throughout the reproductive period, and childhood and adolescence, human physiology undergoes constant change. Therefore, disease processes may manifest differently, and responses to therapies may be different during these transitional periods compared to other physiological states. Therefore, all medical advances, including devices and instruments need to be tested with rigor and reproducibility in these populations. Some technique could be: genetic and proteomic-based biotechnology; microfluidics; nano technology; laser and optical imaging; and signal processing, such as adopting advanced mathematical computations for analyzing biological signals.  Thus, there is clearly an urgent need for R&D in improving existing devices and instruments and/or for developing new devices and instruments while optimizing their utility and safety in the critical care patient groups noted above. They also need to be based on sound bioengineering principles, tested for safety, efficacy, and accuracy of functioning. 

Moreover, despite major advances in biotechnology, nanoparticle, microfluidics, and mobile technologies, research and development efforts directed at introducing new and innovative point of care devices and instruments (or improving the existing ones) for use in the clinical setting or in other patient-centered convenient settings have been limited. There are many unmet needs in the implementation of treatment and monitoring of patients with reproductive disorders, especially infertility.  Only an estimated one out of every four infertile couples in the United States can access all of the care they would need to become pregnant. Concerns have been raised regarding limited and inequitable access to care, high cost and variable availability of services, inconvenience related to timing of treatments that may interfere with work schedules, and difficulty in scheduling procedures such as blood tests and ultrasound used for monitoring in infertility practice. Challenges to fertility care include economic, geographic, sociocultural and ethnic barriers. Research to identify more easily accessible and cost-effective treatments, including laboratory techniques that utilize fewer resources, would improve care.  Therefore, this Funding Opportunity Announcement (FOA) solicits small business corporations (SBCs) to develop, improve and validate methods for point of care testing, devices and instruments which enable evaluation and monitoring in clinical care settings involving obstetric, neonatal, pediatric critical care, reproductive medicine and infertility.

The purpose of this FOA is to support SBIR projects to small businesses using advanced technologies (e.g., bio-chips, microfluidics, and mobile technologies) to develop novel point-of-care (POC) devices and implement existing technologies in clinical settings with a goal to guide diagnostic and therapeutic efforts for obstetric, neonatal, pediatric critical care and reproductive disorders.  Applicants are encouraged to form a multidisciplinary team/network (i.e., from technical to clinical expertise) to develop tools and  devices that will significantly empower patients, physicians, and clinical researchers to better manage or treat these clinical conditions.  It is expected that commercial products or tools will be developed for use in the clinical setting at the POC as a result of this program. 

POC technologies are becoming increasingly valuable tools in improving or enhancing the diagnosis of several clinical conditions.  Utilization of POC technology allows for:

• Greater accessibility to novel technologies for disease diagnosis
• Real-time detection of clinical laboratory measures/biomarkers
• Rapid, standardized, and cost-effective diagnosis and management
• Improved assay/test throughput, decreased assay turn-around times
• Decreased delays in initiation of therapy
• Enhanced communication of test results with multiple parties.

Based on the benefits listed above, these technologies have the potential to play a pivotal role in personalizing medicine, increasing accessibility, improving healthcare delivery, and, ultimately, reducing healthcare costs.  While many of these tools are being developed for clinical application, it is also possible that some of the existing technology could enhance the research enterprise by being used “onsite” for clinical research and trials. Additional benefits of POC-related tools and technologies in clinical research include: easier recruitment, baseline, and follow-up measurements, expedited patient ascertainment and analysis, more rapid dispensation of interventions, better quality control and monitoring of study compliance.  Utilization of POC technology could also allow for patients or research participants to be enrolled in remote, low-resource locations or research poor environments.

One objective of this FOA is to foster collaboration between clinical and bioengineering research communities in the clinical areas of obstetrics, neonatology, pediatric critical care and reproductive medicine for POC testing and device development. It is anticipated that through rigorous collaborative R&D efforts, safe and effective instruments and devices can be developed for use in the evaluation and treatment of men and women with reproductive diseases and disorders including infertility. 

For the topics noted above, projects that address a specific and well-characterized clinical need will be considered of high potential impact.  The technologies developed with funding through this FOA are expected to be integrated systems or, if they are novel components, be easily integrated into existing systems. Some other technical features that are expected are the following: reliability, robustness, safety, simplicity, reliance on the appropriate baseline information, contextual awareness, inclusion of software to support decision-making, and consideration of power consumption.  Proposed tools and technologies should incorporate existing standards and consider regulatory requirements where appropriate.  In addition, improved access to underserved areas, and cost-effectiveness should be highlighted.

Specific areas of research interest that are applicable to pregnancy, neonates, critical care settings and reproductive medicine include, but are not limited to:

• Cardiovascular: Devices and instruments for continuously monitoring blood pressure (BP) non-invasively; methods to accurately measure and monitor cardiac output non-invasively (or minimally invasively); methods to assess tissue perfusion.
• Pulmonary function: devices to assess pulmonary arterial pressures; gas exchange, airway pressure, lung volumes, ventilation/perfusion ratios; improved systems for respiratory support and reduce air-leaks; non-invasive ventilation.
• Cerebrovascular: Devices and instruments for assessing global and regional cerebral blood and cerebrospinal flow, oxygen extraction and utilization of nutritional substrates; autoregulation of cerebral blood flow; and imaging of developing brain for assessing cerebrovascular structural and functional status.
• Maternal and Fetal Monitoring: fetal health assessment tools during pregnancy and peripartum periods.
• Metabolic: Devices and instruments for assessing metabolic substrates, including blood glucose, ketone bodies, lactate/pyruvate; sensors for the assessment of other blood chemical parameters (e.g., serum sodium, potassium, and chloride); devices that monitor Redox potentials accurately, and devices that can perform in-line, continual streaming of pertinent blood levels (such as pH in ECMO patients, sodium in DI patients, etc.).
• Blood concentrations of pharmaceutical agents for clinical care and research purposes.
• Sepsis/Shock/Multi-Organ Failure: Tests for monitoring and treating patients with sepsis and shock, and multi-organ failure.  Devices and instruments for assessing and treating neonatal infections; developing innovative technologies for improving the quality of invasive catheters (including IV, indwelling venous, arterial, umbilical or percutaneous catheters; and various tubes, such endotracheal, nasogastric tubes, suction catheters and component parts for tubes, such as connection hubs,  used in infants during intensive care).
• Studies to improve the accuracy and speed of bacterial and fungal septicemia diagnoses, rapid identification of pathogenic microbial organisms, and assessment of antimicrobial resistance/susceptibility characteristics, inflammatory cytokines and other makers of inflammation utilizing small volumes of blood, urine, saliva, sweat and/or other biological fluids (e.g., fluids from peritoneal and pleural spaces). 
• A nano-sensor or bio-chip device to determine hormone levels from blood and urine samples at the POC. 
• POC device to monitor patients after assisted reproductive technology treatment.
• A portable bio-chip device for DNA extraction and high-throughput genomic analyses, for genotype-guided infertility studies.
• POC ultrasound device to assess ovarian follicular development.
• Implementation of simple, robust, and cost effective methods to measure and transmit blood measurements and information from remote locations, including use of smart phone application.
• Mobile apps to alert and monitor infertility treatment.
• Inexpensive implantable (injectable) nanochips for POC or in home monitoring of hormone or drug levels, e.g. estradiol, progesterone, gonadotropins.
• Development of reliable salivary assays for reproductive hormones and biomarkers.

See Section VIII. Other Information for award authorities and regulations.