Assuming the human molecular monitoring FRO is funded by 2025, will the milestone of developing a 10-analyte device for in situ monitoring be achieved before 2031?

We recommend forecasters start with this document, Forecasting Information for a “Focused Research Organization” to Develop a Modular and Scalable Platform for Human Molecular Monitoring.

From the Federation of American Scientists:

Wearable health electronics are now ubiquitous, but continuous molecular monitoring is only widely available for glucose. Decades of research have expanded continuous monitoring to other molecules, but these techniques are restricted to research labs and remain disconnected from daily human use. We propose a platform to translate and distribute these emerging technologies, enabling the mapping of the time-varying human metabolome and the design of closed-loop devices for personalized health.

###Problem Statement Humans are the best model organisms for humans, yet we have few tools to study human biochemistry in situ and in real time. The Human Metabolome Database lists ~20,000 detected compounds, of which only ~3,000 have been quantified. Even fewer of these biomolecules have been studied with time resolution in longitudinal human studies.

Cardiovascular, metabolic/endocrine and drug pharmacokinetic phenomena are driven by biomolecules varying on the time scale of seconds to minutes to hours, impacting behavior and well-being on similar time scales. Currently, the only way to measure these molecules is through laboratory testing, which is obtrusive to daily life. Moreover, laboratory testing cannot be conducted at the frequency necessary to capture all of these variations.

In contrast, wearable monitors are user-friendly and enable continuous measurements at the correct time scale. These monitors require specially engineered biosensors, since there are a limited number of naturally-occurring enzymes that generate continuous, time-varying electrical signals like those used by continuous glucose monitors, which are currently the only commercially available device of this kind. However, most labs that pioneer biosensing strategies do not develop human-compatible devices and vice versa, creating a chasm between these two areas of research and development.

###Project Concept This project aims to achieve minimally invasive continuous monitoring of 100+ analytes in the human body and deliver devices to researchers. This project will develop a medical device testbed that can use the myriad biosensing strategies pursued by academic labs to develop devices for human experiments. Our technical approach combines synthetic ion channels and conformational switches coupled with a CMOS array to assess many analytes in parallel. We already have access to customized fabrication techniques, and the cost and barriers in designing and manufacturing proteins and silicon sensors are trending downwards.

The project will progress through four interdependent stages:

Survey and prioritize metabolic, hormone, and immune targets that provide the greatest explanatory power for well-being. Select biosensor and transduction systems reported in the literature to interface with our platform. Develop an integrated circuit functionalized with biosensors for parallel multi-analyte sensing packaged in a wearable form factor. Test devices in humans to validate against conventional blood sample analyses. Specify and share validated devices in bulk to catalyze large-scale human field research. Curate a time-varying human metabolome.

<a href="https://fas.org/wp-content/uploads/2023/08/Screen-Shot-2023-08-31-at-9.18.31-AM.png">4 stages</a>

###What Is A Focused Research Organization? Focused Research Organizations (FROs) are time-limited mission-focused research teams organized like a startup to tackle a specific mid-scale science or technology challenge. FRO projects seek to produce transformative new tools, technologies, processes, or datasets that serve as public goods, creating new capabilities for the research community with the goal of accelerating scientific and technological progress more broadly. Crucially, FRO projects are those that often fall between the cracks left by existing research funding sources due to conflicting incentives, processes, mission, or culture. There are likely a large range of project concepts for which agencies could leverage FRO-style entities to achieve their mission and advance scientific progress.

This project suits a FRO-style model because the four research stages require tight feedback loops and standardization and the medical device industry is not incentivized to pursue this kind of research. Private companies typically focus on a handful of molecules most relevant to diabetes care, taking advantage of proven biosensors and predictable insurance reimbursement. A stand-alone, non-profit institute is best suited to standardize and derisk experiments on molecular monitoring to catalyze the formation of a consortium of experimenters. Just as the nonprofit AddGene has standardized and democratized access to genetic material, we seek to develop the analog institution for medical devices.

###How This Project Will Benefit Scientific Progress Human physiology is currently a poorly explored, high-dimensional space, and scientific labs lack the tools to measure human biochemistry over time. The devices developed through this project will first help scientists study specific questions in domains such as disease etiology, human behavior, and drug discovery. Study validity will be enhanced by providing additional molecular time courses which will clarify the relationships between conditions, specific biomarkers, and interventions. Next, these studies will enable the development of a human molecular atlas, similar to the Human Metabolome Database but with time resolution. This database could act as a powerful tool for developing nuanced models of human physiology to uncover previously overlooked phenomena. Finally, similar devices will ultimately become accessible as consumer health products, enabling the next generation of personalized health.