CAREER: Shape-Encoded Electrokinetic Particles for Multiplexed Biosensing

University Of Colorado At Boulder, Boulder CO

Investigators

Abstract

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.