CAREER: Shape-Encoded Electrokinetic Particles for Multiplexed Biosensing

职业：用于多重生物传感的形状编码动电粒子

基本信息

批准号：
2143419
负责人：
Charles Shields
金额：
$ 50万
依托单位：
University of Colorado at Boulder
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2143419&HistoricalAwards=false
关键词：
CAREER Shape Encoded Electrokinetic Particles

项目摘要

Three factors drive the urgent need for improved biosensors. First, success of a therapeutic intervention is linked to the time of initial diagnosis. For pathologies beginning at the cellular or molecular level, early identification of rare disease-associated biomarkers—especially before symptoms manifest—can dramatically improve the likelihood of survival. Second, reliance upon a narrow set of biomarkers can greatly limit the accuracy of initial diagnoses, especially for diseases like cancer. Third, for pathologies that progress rapidly (e.g., hours for many infectious diseases), slow readouts can impair outcomes and increase the cost of intervention. Thus, there remains a need to study new biosensing technologies that address these challenges. This project will develop an active particle-based biosensor where particle speed is associated with the amount of biomarker captured. Particles will have different shapes, each encoding for a different biomarker, enabling the detection of multiple biomarkers simultaneously. The outcome of this work will be a method to capture and quantify heterogeneous biomarkers (e.g., proteins, nucleic acids, exosomes) in a single test. By integrating concepts in physics, chemistry, and biology, this project will appeal to high school students by highlighting the exciting and multidisciplinary nature of biosensing. This outreach component will be accomplished through a “reverse science fair”, whereby graduate students will present their work to a panel of high school student judges through interactive demos. The integrated research and education plan will also include a mentorship program that engages local high school students through year-long capstone projects to encourage their participation in biosensing research as a frontier scientific discipline. The goal of this CAREER project is to understand the factors that influence the motion of electrokinetic active particles to enable a new and efficient method of detecting heterogeneous biomarkers. Electrokinetic active particles are particles with asymmetric surface polarizabilities. At high electric field frequencies, conductive regions on the particles induce a charged screening cloud in the proximate fluid, driving nearby ions to flow more rapidly than ions near the dielectric regions. Particles subsequently propel by induced charge electrophoresis (ICEP). The capture of biomarkers by affinity ligands on the conductive regions of the particles alters their speed of propulsion. The central hypothesis of this research is that the specific capture of biomarkers on the conductive regions of the particles will enable the direct quantification of biomarker concentration by basic microscopy and particle tracking. To test this hypothesis, the project will: (1) study the relationship between biomarker size, charge density, and concentration on ICEP using numerical predictions and experiments, (2) study the capture specificity of particles with electrically permissive antifouling coatings, (3) examine sensitivity as a function of antibody coating density, and (4) validate the efficacy of the biosensors to simultaneously detect a diverse panel of biomarkers from blood in a single assay.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.

三个因素推动了对改进生物传感器的迫切需求。首先，对于从细胞或分子水平开始的病理学，早期识别罕见疾病相关的生物标志物（尤其是在症状出现之前）与治疗干预的成功有关。其次，对一组狭窄的生物标志物的依赖会极大地限制初始诊断的准确性，特别是对于癌症等疾病。读数可能会影响结果因此，仍然需要研究新的生物传感技术来应对这些挑战，该项目将开发一种基于活性颗粒的生物传感器，其中颗粒速度与捕获的生物标记物的数量相关。，每个编码不同的生物标志物，从而能够同时检测多个生物标志物，这项工作的成果将是一种通过将概念整合到单个测试中来捕获和量化异质生物标志物（例如蛋白质、核酸、外泌体）的方法。物理、化学和生物学，该项目将通过强调生物传感的令人兴奋和多学科的性质来吸引高中生。这一外展部分将通过“逆向科学博览会”来完成，因此研究生将向一组小组展示他们的工作。综合研究和教育计划还将包括一项指导计划，通过为期一年的顶点项目吸引当地高中生参与，作为这一前沿科学学科的目标。项目是为了了解影响动电活性粒子运动的因素，以实现检测异质生物标志物的新且有效的方法动电活性粒子是具有不对称表面极化率的粒子，在高电场频率下，粒子上的导电区域会在其中产生带电屏蔽云。邻近的流体，驱动附近的离子比介电区域附近的离子更快地流动，随后通过诱导电荷电泳 (ICEP) 推动颗粒导电区域上的亲和配体捕获生物标记物。这项研究的中心假设是，对颗粒导电区域上的生物标志物进行特异性捕获将能够通过基本显微镜和颗粒跟踪来直接量化生物标志物浓度。 1) 使用数值预测和实验研究生物标记物大小、电荷密度和 ICEP 浓度之间的关系，(2) 研究具有电许可防污涂层的颗粒的捕获特异性，(3) 检查作为抗体涂层函数的灵敏度密度，(4) 验证生物传感器在一次检测中同时检测血液中多种生物标记物的功效。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响进行评估，被认为值得支持审查标准。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Motion of an active bent rod with an articulating hinge: exploring mechanical and chemical modes of swimming

DOI：
10.3389/fphy.2023.1307691
发表时间：
2023-12
期刊：
Frontiers in Physics
影响因子：
3.1
作者：
Ritu R. Raj;Arkava Ganguly;Cora Becker;C. W. Shields;Ankur Gupta
通讯作者：
Ritu R. Raj;Arkava Ganguly;Cora Becker;C. W. Shields;Ankur Gupta

Magnetically locked Janus particle clusters with orientation-dependent motion in AC electric fields.

磁锁 Janus 粒子簇在交流电场中具有方向相关的运动。

DOI：
10.1039/d3nr03744d
发表时间：
2023
期刊：
Nanoscale
影响因子：
6.7
作者：
Lee,JinGyun;Thome,CooperP;Cruse,ZoeA;Ganguly,Arkava;Gupta,Ankur;Shields4th,CWyatt
通讯作者：
Shields4th,CWyatt

Microrobots for Biomedicine: Unsolved Challenges and Opportunities for Translation