The Aptamer BioResistor: A Broadly Applicable Protein Biosensor with Dip-and-Read Simplicity for Point-of-Care Diagnostics

由个人医生进行的尿检并不是用来检测任何疾病的。该项目的目标是开发一种简单、一次性使用的传感器，可以浸入尿液样本中，用于检测各种疾病，包括尿路感染、肾脏疾病和癌症。这些传感器必须便宜、可靠、速度足够快，才能在医生的办公室里几分钟内检测尿液。目前还没有具备这种性能的传感器，但在之前的研究中，已经开发出一种新的传感器设计，可以满足这些要求。它被称为阻抗感应式生物电阻或ITBR。ITBR使用病毒颗粒作为“受体”来进行感知。但是，ITBR所需的能够检测疾病的病毒颗粒很难生产出来。该项目的目标是改造ITBR，以便可以使用一种更常见、更多功能的受体，称为适体，以取代病毒颗粒。针对某些疾病的适体已经可以在商业上买到。对于其他疾病，研究人员将准备适配子。适体比病毒小得多，因此ITBR的设计需要适当修改。该项目的更广泛影响包括将高中生纳入暑期研究项目，在该项目中，他们将学习如何制造含有适体的ITBR。该项目的目标是开发一种适体生物抵抗器(AptBR)，在先前研究中开发的阻抗感应式生物抵抗器(ITBR)中，适体被取代作为M13病毒颗粒的受体。该项目的智能价值在于开发和表征了一种超薄(~100 nm)适配子--提供了符合BioResistor体系结构的生物亲和层。AptBR需要一种快速和高重复性的适体导电聚合物复合薄膜沉积工艺，该工艺包括：(1)。将适配子提供给接触溶液，(2)促进目标蛋白对生物亲和层的渗透，以及(3)利用在ITBR中工作的独特机制，电转导目标蛋白的结合。随着AptBR生物亲和层和使用它的新生物传感器的明确设计规则，AptBR将从这个项目中诞生。该项目有四个更广泛的影响：首先，AptBR将增加可以使用BioResistor架构测量的疾病标记物的数量。其次，AptBR将能够在护理点运行，以检测动物和人类的这些疾病。第三，该提案支持面向高中生的推广项目NeXTech 202X，提供针对该项目生物传感器开发主题的动手实验室科学和课堂培训。第四，这笔赠款将支持强调多才多艺和解决问题的研究生培训。这些研究生将获得广泛的工具经验，包括电子显微镜、XPS、AFM和许多其他工具，以及电化学和微制造方法。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The urine test administered by an individual’s physician is not designed for the detection of any diseases. The goal of this project is to develop a simple, single-use, disposable sensor that can be dipped into a urine sample for the purpose of detecting a variety of diseases, including urinary tract infections, kidney disease, and cancers. These sensors must be inexpensive, reliable, and fast enough to test urine in a few minutes in a doctor’s office. Sensors capable of such performance are not yet available, but in previous research, a new sensor design was developed that could meet these requirements. It’s called the Impedance Transduced BioResistor or ITBR. The ITBR uses virus particles as “receptors” to do sensing. But virus particles capable of detecting disease, as required for the ITBR, are difficult to produce. The goal of this project is to adapt the ITBR so that a more common and more versatile receptor called an aptamer can be used in place of virus particles. Aptamers for some diseases are already commercially available. For other diseases, the investigators will prepare the aptamers. Aptamers are much smaller than viruses so the design of the ITBR will need to be appropriately modified. The Broader Impacts of this project include the inclusion of high school students into a summer research program in which they will learn how to make ITBRs containing aptamers.The goal of this project is to develop an Aptamer BioResistor (AptBR), in which aptamers are substituted as receptors for M13 virus particles in the Impedance-Transduced BioResistor (ITBR) developed in previous research. The Intellectual Merit of this project is in the development and characterization of an ultra thin (~100 nm) aptamer-presenting a bioaffinity layer that is compliant with the BioResistor architecture. The AptBR requires a process for the rapid and highly reproducible deposition of aptamer-conductive polymer composite films that: (1). present aptamers to a contacting solution, (2) facilitate permeation of the bioaffinity layer by target protein, and (3) electrically transduce the binding of a target protein, using the unique mechanism that operates in the ITBR. With clear design rules for the AptBR bioaffinity layer and for a new biosensor employing it, the AptBR will emerge from this project. The project has four Broader Impacts: First, the AptBR will increase the number of disease markers that can be measured using the BioResistor architecture. Second, the AptBR will be able to operate at the point-of-care to detect these diseases in animals and humans. Third, the proposal supports NEXTech 202X, an outreach program for high school students, providing hands-on laboratory science and classroom training that is keyed to the biosensor development theme of the project. Fourth, this grant will support graduate training emphasizing versatility and problem solving. These graduate students will become experienced with a broad range of tools including electron microscopy, XPS, AFM, and many others, as well as electrochemistry and microfabrication methods.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.