Wearable sensor-actuator microsystems for the continuous monitoring of reproductive hormones during assisted fertilization - WEREPRO

荷尔蒙相关的变化是怀孕计划问题的主要原因之一。许多生育治疗包括注射激素和定期测量血液中的激素，以防止卵巢过度刺激或确定合适的受精或摘除胚珠的时间。因此，需要精确控制注射和循环激素的水平。在临床科学家的支持下，该项目旨在解决使用可穿戴设备实时监测生殖激素的挑战。随之而来的及时刺激和成熟可能有助于增加成功怀孕或取卵的机会，减少阴道内超声检查或频繁抽血的需要。传统的测量方法是基于对血清、唾液或尿液的检测，这对连续筛查施加了几个限制。一方面，频繁的血液检测会认为过度采集样本是一种侵入性的方式。另一方面，唾液只能用于类固醇激素，而不能用于多肽类激素。此外，从唾液中获得的结果可能会受到食物中含有的外源激素或细菌的影响。真皮间质液(ISF)是一种合适的替代物，因为它可以很容易地用微创设备收集，并且具有与血浆相似的蛋白质组学特征。此外，它不会凝固，使其更安全地保存传感器操作以及患者的健康。该项目的目的是开发一种配备生物传感器的可穿戴设备，用于ISF中女性生殖激素的连续监测。该设备将有助于个性化激素治疗，并减轻接受生育治疗的患者面临的压力。为了实现该项目的目标，两个合作伙伴将根据他们的专业知识共同努力。Tu Dresden在纳米材料生物传感器方面拥有长期经验，他将专注于场效应晶体管的开发，将其作为高灵敏度的纳米设备，以传递激素生物识别的信号。IfW-Dresden拥有智能执行器方面的专业知识，将开发微阀控制的智能微针阵列，用于按需控制ISF采样。双方将通过微流控技术共同组装整个设备，并将与临床科学家合作进行临床验证。总体而言，该项目将为女性荷尔蒙监测提供一种有利的方法，与血液分析相比，降低侵袭性，并实施耐磨性。未来的其他好处包括通过消除过量荷尔蒙注射的副作用增加安全性，个性化治疗，通过将设备集成到物联网中心系统来实现远程患者和临床医生互动，以及创建将数据与其他重要参数相结合的数字双胞胎，所有这些都对成功的不孕不育治疗产生积极影响。

Hormonal-related changes are one of the main causes of problems with pregnancy planning. Many fertility treatments include hormone injections and periodic hormone measurements in blood, in order to prevent ovary overstimulation or to determine the suitable insemination or ovule extraction times. Therefore, the levels of injected and circulating hormones need to be precisely controlled. With the support of clinical scientists, this project aims at addressing the challenge of real-time monitoring of reproductive hormones using a wearable device. The consequent timely stimulation and maturation might help to increase the chances of successful pregnancy or ovum retrieval, reducing the need of intravaginal ultrasound inspection or frequent blood extractions. Traditional measurements are based on testing of blood serum, saliva or urine, which impose several limitations in terms of continuous screening. On one hand, frequent measurements in blood would suppose excessive sample collection in an invasive way. On the other hand, saliva can only be used for steroid hormones but not for peptide-based ones. In addition, results obtained from saliva may be affected by exogenous hormones contained in food or by bacteria. Dermal interstitial fluid (ISF) is a suitable alternative, since it can be easily collected with micro-invasive devices and has similar proteomic profile to plasma. Besides, it does not coagulate, making it more secure to preserve sensor operation as well as for patients’ health. The aim of the hereby proposed project is to develop a wearable device equipped with a biosensor for continuous female reproductive hormones monitoring in ISF. The device will help to personalize hormone therapy and reduce the stress the patients undergoing fertility treatments are exposed to. To reach the goal of the project, two partners will join efforts based on their expertise. TU Dresden, with long experience in nanomaterials-based biosensors, will focus on the development of field-effect transistors as highly sensitive nanodevices to transduce the signal of hormone biorecognition. IFW-Dresden, with expertise on smart actuators, will develop microvalve-controlled smart microneedle arrays for the controlled ISF sampling on demand. Both partners will work together on the assembly of the whole device via microfluidics and will clinically validate it in collaboration with clinical scientists. Overall, the project will provide an advantageous approach for female hormone monitoring, reducing invasiveness compared to blood analysis and implementing wearability. Additional future benefits include safety increase by eliminating side effects of excessive hormonal injections, personalizing the therapy, enabling remote patient-clinician interaction by integrating the device into an Internet of Things Hub system and the creation of digital twins combining the data with other vital parameters, all with a positive impact toward successful infertility treatments.