# A non-invasive metabolic sensor for improving success in IVF

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $242,250

## Abstract

ABSTRACT
Embryos cultured external to the body are exposed to non-physiologic conditions that can impair the health of
the future adult. Moreover, culture stress reduces immediate embryo viability and implantation success,
motivating multiple embryo transfers and leading to high rates of multiple pregnancies. These pregnancies are
risky for fetus and mother and exhibit a high healthcare cost burden. To address this, embryos are screened
based on early-stage morphology to identify the healthiest for transfer, but this approach achieves limited
success and is highly dependent on the individual conducting the test. An accurate and objective screening
method would increase implantation rates and reduce the need for multiple transfers, in addition to yielding
healthier offspring. The objective of this project is to develop a new technology for noninvasive IVF embryo
selection. Dr. Paolo Rinaudo, Co-I on this grant, is a Reproductive Endocrinologist working at the UCSF Center
for Reproductive Health which performs >2000 IVF procedures per year and has commitment to research.
Through experience derived from two decades of work in IVF, he identified that current methods for screening
embryos are inadequate, with the gold standard, morphological selection, achieving a positive predictive value
of just 30%. While an embryo may appear morphologically healthy, it may not be molecularly healthy, which may
affect the long-term development of the fetus. Among his two decades of research on cultured embryos and IVF
is the finding that ex vivo culture can stress embryos and drive Warburg-like metabolism. In addition, culture
stress has now been correlated to long-term negative health outcomes, including abnormal placental
development, metabolic dysfunction, hypertension, and diabetes. Dr. Rinaudo hypothesized that metabolically
active embryos lower their culture droplet pH, similar to how Warburg metabolism acidifies the environment
around cancer cells, thereby affording a simple way to select the best embryos for transfer. His research has
confirmed this, but the technique cannot be translated to practice because there is no effective and reliable pH
measuring method for the culture droplet due to its tiny volume. Armed with this concept, he reached out to Dr.
Adam Abate, a physicist and engineer at UCSF. Dr. Abate is a leader in microfluidics and nanotechnology with
a record of developing and translating health care technologies to practice, having founded multiple companies
commercializing his inventions, including Fluent Biosciences (genomics), Mission Bio (oncology diagnostics) and
Scribe (cell & gene therapy). Together, Drs. Rinaudo and Abate have designed a novel hydrogel biosensor that
non-invasively measures culture droplet pH. Being an IVF clinician, Dr. Rinaudo is aware of the regulatory and
practical constraints of IVF operations and thus ensured the design is feasible for this setting by making it simple,
non-invasive, and cost-effective. This grant ...

## Key facts

- **NIH application ID:** 10894790
- **Project number:** 5R21HD109079-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Adam R. Abate
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $242,250
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894790

## Citation

> US National Institutes of Health, RePORTER application 10894790, A non-invasive metabolic sensor for improving success in IVF (5R21HD109079-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894790. Licensed CC0.

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