APTERA II - Electromagnetic THz- and mm-wave Sensors for African Trypanosomes using RNA Aptamer-Derivatized Surface Layers

我们合作研究的目标是开发一种用于检测非洲锥虫的电磁（EM）传感器设备。锥虫是引起非洲锥虫病的单细胞生物，这是一种寄生虫病，也被称为非洲昏睡病。如果不及时治疗，昏睡病是致命的，因此，早期检测受感染患者血液和/或脑脊液中的寄生虫细胞对卫生工作者和临床医生至关重要。如最初提出的，EM传感器在mm和THz频率区域中操作，并且为了促进寄生虫与感觉表面的结合，它们用所谓的适体分子共价官能化。适体是合成的生物分子亲和试剂，在这种情况下，其被设计为特异性粘附于锥虫细胞的表面。在第一个资助期内，我们能够证明我们的EM-适配器方法的普遍适用性，在第二个资助期内，我们现在建议使用生成的数据和知识来制定第一个原型诊断设备的下一步。具体来说，我们打算增加感觉表面的灵敏度，以降低检测限，从而能够检测到甚至非常低数量的寄生虫。此外，我们建议将我们的检测原理扩展到“潮湿条件”，以便能够处理和测量“真实”的生物样品，如锥虫感染的血液或血清标本。这些“湿样品”的电磁特性将被彻底表征。我们认为欺骗等离子体激元结构和一个特殊的系统的两个耦合谐振器，以实现增加的灵敏度和测量的能力，在潮湿的条件下，由于水的高损失。我们还建议将我们的研究扩展到更复杂的适体衍生表面，如多功能和多层适体表面，我们建议生成适体/纳米抗体混合表面，以进一步降低检测限。该提案包括所有必要步骤，以证明EM-适体传感器方法的“原理证明”，并旨在为设计快速、稳健和低成本检测非洲昏睡病的原型设备奠定基础。作为与基辛格教授合作努力的一部分，计划建造第一个集成芯片，该芯片在适体传感器旁边包含用于信号生成和检测的所有必要电子电路。

The goal of our collaborative research effort is the development of an electromagnetic (EM) sensor device for the detection of African trypanosomes. Trypanosomes are single cell organisms that cause African trypanosomiasis, a parasitic disease that is also known as African sleeping sickness. If left untreated, sleeping sickness is fatal and thus, the early detection of parasite cells in the blood and/or the cerebrospinal fluid of infected patients is for health workers and clinicians crucial. As initially proposed, the EM-sensors operate in the mm- and THz-frequency region and in order to facilitate the binding of parasites to the sensory surface they are covalently functionalized with so-called aptamer molecules. Aptamers are synthetic, biomolecular affinity reagents, which in this case have been designed to specifically adhere to the surface of trypanosome cells. In the 1st funding period we were able to demonstrate the general applicability of our EM-aptasensor approach and for the 2nd funding period we now propose to use the generated data and knowledge to make the next steps towards a first prototype diagnostic device. Specifically, we intend to increase the sensitivity of the sensory surface to lower the detection limit to be able to detect even very low numbers of parasites. Furthermore, we suggest to extend our detection principle to "wet conditions" to be able to handle and measure "true" biological samples such as trypanosome-infected blood or serum specimen. The electromagnetic properties of these “wet samples” will be thoroughly characterised. We consider spoof plasmonic structures and a special system of two coupled resonators to achieve increased sensitivity and the ability to measure under wet conditions with high losses due to the water. We also propose to expand our investigation into more sophisticated aptamer-derivatized surfaces such as multifunctional and multilayered aptamer surfaces and we propose to generate aptamer/nanobody hybrid surfaces to potentially lower the detection limit even further. The proposal includes all necessary steps to demonstrate “proof-of-principle” of the EM-aptasensor approach and is intended to provide the groundwork for the design of a prototype-device for a fast, robust and low cost detection of African sleeping sickness. The construction of a first integrated chip that contains next to the aptasensor all the necessary electronic circuitry for signal generation and detection is planned as part of a cooperative effort together with Prof. Kissinger.