A non-invasive metabolic sensor for improving success in IVF

用于提高 IVF 成功率的非侵入性代谢传感器

基本信息

批准号：
10741730
负责人：
Adam R. Abate
金额：
$ 20.19万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10741730
关键词：
Abate Address Adult Affect American Awareness Beta Cell Biological Sciences Biomedical Engineering Biomedical Research Biosensing Techniques Biosensor Birth Cell Therapy Chemicals Clinic Clinical Complex Country Culture Media DNA Data Denmark Development Diabetes Mellitus Diagnostic Drops Embryo Embryo Transfer Endocrinologist Engineering Ensure Environment Epigenetic Process Exhibits Exposure to Fertility Fetus Foundations Frequencies Functional disorder Future Genomics Glucose Intolerance Goals Grant Health Health Care Costs Health Technology Human Hydrogels Hypertension Impaired health Implant Individual Japan Lipids Marketing Maternal Health Measurement Measures Metabolic Metabolic dysfunction Metabolism Methods Microfluidics Mission Mitochondria Modification Molecular Morphology Mothers Multiple Birth Offspring Multiple Pregnancy Mus Nanotechnology National Institute of Child Health and Human Development Oncology Outcome Oxidative Stress Physicians Placentation Predictive Value Pregnancy Pregnancy Rate Procedures Proteins Regulation Reporting Reproductive Health Research Risk Sampling Science Services Stress Techniques Technology Testing Translating Translations Uterus Variant Woman Work abortion assisted reproduction cancer cell care costs commercialization cost effective design diagnostic value embryo culture experience extracellular gene therapy implantation improved invention meter mouse model natural Blastocyst Implantation neonatal health new technology novel offspring operation oxidation particle preimplantation prototype reproductive screening sensor skills stress reduction success temporal measurement

Abate Address Adult Affect American Awareness Beta Cell Biological Sciences Biomedical Engineering Biomedical Research Biosensing Techniques Biosensor Birth Cell Therapy Chemicals Clinic Clinical Complex Country Culture Media DNA Data Denmark Development Diabetes Mellitus Diagnostic Drops Embryo Embryo Transfer Endocrinologist Engineering Ensure Environment Epigenetic Process Exhibits Exposure to Fertility Fetus Foundations Frequencies Functional disorder Future Genomics Glucose Intolerance Goals Grant Health Health Care Costs Health Technology Human Hydrogels Hypertension Impaired health Implant Individual Japan Lipids Marketing Maternal Health Measurement Measures Metabolic Metabolic dysfunction Metabolism Methods Microfluidics Mission Mitochondria Modification Molecular Morphology Mothers Multiple Birth Offspring Multiple Pregnancy Mus Nanotechnology National Institute of Child Health and Human Development Oncology Outcome Oxidative Stress Physicians Placentation Predictive Value Pregnancy Pregnancy Rate Procedures Proteins Regulation Reporting Reproductive Health Research Risk Sampling Science Services Stress Techniques Technology Testing Translating Translations Uterus Variant Woman Work abortion assisted reproduction cancer cell care costs commercialization cost effective design diagnostic value embryo culture experience extracellular gene therapy implantation improved invention meter mouse model natural Blastocyst Implantation neonatal health new technology novel offspring operation oxidation particle preimplantation prototype reproductive screening sensor skills stress reduction success temporal measurement

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项目摘要

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 will develop the technology and validate its efficacy in a mouse model of IVF, providing critical data for a follow-on R01. The project is thus based on a rigorous scientific foundation, decades of clinical experience, and comprises a team capable of translating science discoveries to the clinic.

抽象的培养在身体外部培养的胚胎处于可能损害健康状况的非生理条件未来的成年人。此外，培养压力降低了立即的胚胎生存力和植入成功，激励多个胚胎转移并导致多次妊娠率高。这些怀孕是胎儿和母亲的风险，表现出很高的医疗费用负担。为了解决这个问题，筛选胚胎基于早期形态以识别最健康的转移，但是这种方法有限成功，高度依赖于进行测试的个人。准确和客观的筛选方法还会增加植入率并减少对多次转移的需求，此外更健康的后代。该项目的目的是为非侵入性IVF Embryo开发新技术选择。 Paolo Rinaudo博士，该赠款的Co-I，是在UCSF中心工作的生殖内分泌学家对于生殖健康，每年执行> 2000 IVF程序，并致力于研究。通过IVF中二十年的工作的经验，他确定了当前的筛查方法胚胎不足，具有黄金标准，形态学选择，实现了积极的预测价值仅30％。虽然胚胎可能在形态上看起来健康，但它可能不是分子健康的，这可能影响胎儿的长期发展。在他关于培养的胚胎和IVF的二十年研究中是在体内培养物可以强调胚胎并推动类似沃堡的新陈代谢的发现。另外，文化现在的压力与长期负面健康结果相关，包括异常胎盘发育，代谢功能障碍，高血压和糖尿病。 Rinaudo博士假设该代谢活跃的胚胎降低了培养液滴pH，类似于沃堡新陈代谢如何酸化环境在癌细胞周围，从而为选择最佳转移的胚胎提供了一种简单的方法。他的研究有确认了这一点，但是该技术不能转化为实践，因为没有有效且可靠的pH 由于其体积很小，培养液滴的测量方法。他凭借这个概念，与博士联系。亚当·阿巴特（Adam Abate），UCSF的物理学家兼工程师。 Abate博士是微流体和纳米技术的领导者创立了多家公司的发展和翻译医疗保健技术的记录商业化他的发明，包括流利的生物科学（基因组学），任务生物（肿瘤学诊断）和抄写员（细胞和基因治疗）。在一起，博士。 Rinaudo和Abate设计了一种新型的水凝胶生物传感器非侵入性测量培养液滴pH。作为IVF临床医生，Rinaudo博士意识到监管机构 IVF操作的实际限制，因此通过使其简单，无创和具有成本效益。该赠款将开发该技术并在鼠标模型中验证其功效 IVF的of，为后续R01提供关键数据。因此，该项目基于严格的科学基础，数十年的临床经验，包括一个能够将科学发现转化为诊所的团队。