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

该项目的更广泛的影响/商业潜力是：(1)显著提高不育夫妇的生育率，特别是患有非阻塞性无精子症（NOA）的患者的生育率。NOA在1%的男性人口中发现，在高达20%的男性不育病例中发现，并与射精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人工授精样本以分离高质量精子，或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，再次导致不孕夫妇的生育率提高和成本降低。(3)精子加工市场可能是巨大的：如果美国大约50%的实验室使用这种系统，每年的总周期将约为44,000次。以每台250美元的成本计算，仅NOA的市场规模就将达到1100万美元。人工授精和微人工授精的用途不仅在于其分离精子的潜在有效性，而且还在于减少了技术人员的工作量。在美国，人工授精的数量要高得多，这将为每年至少3000万美元的市场扩张增加额外的空间。欧洲的人工授精率要高得多，亚洲的人工授精率也在不断增长，这表明整个市场的规模很可能超过1亿美元/年。这项小型企业技术转移研究（STTR）第一阶段项目旨在改进目前用于非阻塞性无精子症（NOA）患者的显微外科睾丸精子提取（mTESE）临床程序，其中包括很大比例的不育男性（10% - 20%）。对于患有非阻塞性无精子症（NOA）的患者来说，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很低。mTESE程序目前依赖于手工显微镜检查睾丸组织标本，以识别精子的mTESE样本，精子细胞浓度非常低，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）和劳动密集型的过程。该项目涉及开发一种微流体系统，以提高NOA患者的精子恢复率。微流体系统将利用无标记细胞分离技术将精子从其他细胞/生物颗粒中分离出来，然后将分离出来的精子分组进行冷冻保存。该项目的最终结果将是一个系统，该系统输入mTESE样本并输出可在群体水平上冷冻保存的精子群。

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.