STTR Phase I: Development of a Novel Microfludics Device to Optimize Sperm Retrieval and Storage from Microsurgical Testicular Sperm Extraction

STTR 第一阶段：开发新型微流体装置，以优化显微外科睾丸精子提取中的精子回收和储存

• 批准号: 1549659
• 负责人: Raheel Samuel
• 金额: $ 22.5万
• 依托单位: NANONC inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1549659&HistoricalAwards=false
• 关键词: STTR; Phase; Development; Novel; Microfludics

The broader impact/commercial potential of this project is (1) the significant improvement in fertility rates among infertile couples and especially for patients suffering from non-obstructive azoospermia (NOA), which is found in 1% of the male population and in up to 20% of male infertility cases and is associated with non-measurable levels of sperm in the ejaculate. Automated systems to collect sperm from these samples would greatly reduce costs and failure rates. (2) Second, the proposed devices will be used in the preparation of insemination samples to isolate high quality sperm, or in the removal of white blood cells from a heterogeneous sample to yield sperm samples that are suitable for intrauterine insemination, again leading to higher fertility rates and lower costs for infertile couples. (3) The sperm processing market could be substantial: If approximately 50% of labs in the US used this system, the total cycles per year would be approximately 44,000. At a cost of $250/each, the market for NOA alone would be $11M. The utility in insemination and microTESE come not only in its potential effectiveness to isolate sperm but also in the decreased workload on technicians. The number of inseminations is much higher in the US and would add additional room for market expansion of at least $30M/year. Rates of insemination are much higher in Europe and growing in Asia, suggesting the overall market could readily be more than $100M/year.This Small Business Technology Transfer Research (STTR) Phase I project is about improving current clinical procedures for Microsurgical Testicular Sperm Extraction (mTESE) when used with patients suffering from non-obstructive azoospermia (NOA), which includes a large proportion of infertile men (10% - 20%). For patients suffering with non-obstructive azoospermia (NOA), obtaining sperm presents a great challenge, and thus, the rate of pregnancy for this group of infertile patients remains low. mTESE procedures currently rely on manual microscopic inspection of testicular tissue specimens to identify sperm in a mTESE sample that has very low concentration of sperm cells and a large concentration of other cells and bioparticles. Hence extracting sperm from mTESE samples is a long, inefficient (low sperm recovery) and labor-intensive process. This project involves the development of a microfluidic system that improves sperm recovery rates specifically from NOA patients. The microfluidic system would utilize label-free cell separation technologies to separate sperm from other cells/bioparticles and then sort the separated sperm in groups for cryopreservation. The final outcome of the project would be a system that inputs a mTESE sample and outputs groups of sperm that can be cryopreserved at the group-level.

该项目更广泛的影响/商业潜力是 (1) 显着提高不孕夫妇的生育率，特别是患有非梗阻性无精子症 (NOA) 的患者，该病存在于 1% 的男性人口中，并且高达20% 的男性不育病例与精液中不可测量的精子水平有关。从这些样本中收集精子的自动化系统将大大降低成本和失败率。 (2) 其次，所提出的装置将用于制备授精样本以分离高质量精子，或用于从异质样本中去除白细胞以产生适合宫内授精的精子样本，这再次导致更高的生育率和降低不孕夫妇的费用。 (3) 精子处理市场可能很大：如果美国大约 50% 的实验室使用该系统，每年的总周期将约为 44,000 次。以每个 250 美元的成本计算，仅 NOA 的市场就将达到 1100 万美元。 授精和 microTESE 的实用性不仅在于其分离精子的潜在有效性，还在于减少了技术人员的工作量。美国的人工授精数量要高得多，这将为市场扩张增加至少 3000 万美元/年的额外空间。 欧洲的授精率要高得多，亚洲的授精率也在增长，这表明整体市场可能超过 1 亿美元/年。这个小型企业技术转让研究 (STTR) 第一阶段项目旨在改进当前显微外科睾丸精子提取的临床程序(mTESE) 用于患有非梗阻性无精症 (NOA) 的患者，其中包括很大比例的不育男性 (10% - 20%)。对于非梗阻性无精症（NOA）患者来说，获得精子是一个巨大的挑战，因此这组不孕患者的怀孕率仍然较低。 mTESE 程序目前依靠对睾丸组织样本进行手动显微镜检查来识别 mTESE 样本中的精子，该样本中的精子细胞浓度非常低，而其他细胞和生物颗粒浓度很高。因此，从 mTESE 样本中提取精子是一个漫长、低效（精子回收率低）且劳动密集型的过程。该项目涉及微流体系统的开发，该系统可提高尤其是 NOA 患者的精子回收率。微流体系统将利用无标记细胞分离技术将精子与其他细胞/生物颗粒分离，然后将分离的精子分组进行冷冻保存。该项目的最终成果将是一个输入 mTESE 样本并输出可在群体水平上冷冻保存的精子组的系统。