This Career award by the Biomaterials program in the Division of Materials Research to University of Michigan is to study the molecular design principles of bio-conjugated polymer hybrid materials in order to develop self-signaling and signal amplifying bio-microarrays based on nucleic acids/proteins-conjugated polymers. Biological molecules such as nucleic acids and proteins have unique specificity in recognition. But fast and reliable detection of these diagnostically important biological molecules remains a significant challenge especially given the difficulty in devising an effective label-free and sensitive detection strategy. On the other hand, conjugated polymers (CPs) can respond very sensitively to a variety of environmental stimuli via changes to their physical properties, e.g. changes in color and fluorescent emission. Earlier studies have expended signal amplifying property of synthetic CPs for high sensitivity in many molecular sensor designs. To develop highly sensitive and highly selective biosensors for these biomolecules, this award will devise bio-conjugated polymer hybrid materials where biological materials are the recognition receptor and CPs are the reporters generating a sensory signal. These studies will address the most important design principle to combine a biological receptor and a conjugated polymer so that a selective recognition event at the receptor site can produce a sensitive, amplified signal from the conjugated polymer reporter. The most valuable knowledge that would come out of these studies will be molecular design principles of conjugated polymers and bio-conjugation and an assembly/fabrication strategy for the development of self-signaling and signal amplifying biosensor arrays. The relationship between the chemical structure of a conjugated polymer and its assembly with biological receptors and their effects on sensor sensitivity and selectivity will be systematically investigated to reveal the necessary design principles. The design considerations of each component to allow for properties necessary to the molecular sensor will provide insight in molecular biosensor design. The proposed studies will promote molecular-level understanding in students at various levels on the relationship between organic/polymeric molecular design and the properties of such materials through incorporating results from the proposed research into ongoing curriculum and outreach program development. The main components of the proposed research cover broad disciplines of science including molecular design, chemical synthesis, polymer synthesis, molecular self-assembly, device fabrication, and performance characterization. These multidisciplinary components will be integrated into a larger educational effort to (1) offer engineering students a solid foundation of molecular design principles, structure-property relationships, synthetic methodology, and the assembly of organic and polymeric materials, (2) promote engineering students' abilities to devise advanced novel soft materials and associated devices, (3) prepare engineering students to conduct multidisciplinary research involving materials and biology. Students will learn how to consider essential properties of molecular biosensors and integrate each component into sensor design.
Low cost, reliable detection of clinically important biological molecules remains a significant challenge especially given the difficulty in devising an effective label-free detection strategy. In this NSF Career project, we devised a sensory material system with a built-in self-signaling and signal amplifying capability in order to provide a universal transducer for a specific assay of diverse set of target biological molecules. Three scientific and technological achievements have been made. First, a unique dual-signaling sensory system based on polydiacetylenes (PDAs) has been devised. PDA is a unique conjugated polymer having a pressure-sensitive color change from blue. We developed self-assembly strategies to make PDA liposomes and nanofibers and tether rationally designed capture molecules at the surface of PDA liposomes. We rationally designed the sensory system in such a way that the recognition events between the capture molecule and its desired target molecule produce steric repulsion and subsequently turn on the pressure-sensitive color change of the PDA and red fluorescent generation at the same time. We systematically investigated the effects of the target size and incorporation of lipids into the PDA liposome on the intensity of the sensory signal. The obtained results were used in the development of potassium sensor, mercury sensor, melamine detection, nerve agent detection, aminoglycosidic antibiotic sensor, influenza virus A detection, and PDA nanoparticles for immunofluorescence labeling and multiphasic microparticles of PDA for high throughput detections of multiple targets. Second, a molecular design principle to realize completely water-soluble and highly emissive conjugated polyelectrolytes (CPEs) has been established. These polymers have been further utilized in self-signaling and signal-amplifying DNA microarrays, a prostate specific antigen detection sensor, and CPE-antibody hybrid molecules for live cell imaging. Third but not least, a molecular design principle of novel purely organic phosphorescent materials has been developed from a byproduct obtained during the CPEs development. Bright phosphorescent materials have been synthesized based on the devised directed heavy atom effects. This novel class of materials is much cheaper than conventional phosphors, stable, color-tunable, and can be easily synthesized and therefore will be potentially very useful for display, solid-state lighting, and biosensors. The obtained outcomes have been disseminated through 21 journal publications with 4 journal covers, 16 conference presentations, and 73 seminar talks. Two patents have been awarded. The most valuable knowledge obtained through the project are the molecular design principles of conjugated polymers and bioconjugation and an assembly/fabrication strategy for the development of self-signaling and signal amplifying biosensor arrays. The relationship between the chemical structure of a conjugated polymer and its assembly with biological receptors and their effects on sensor sensitivity and selectivity systematically provided insight in molecular biosensor design. The outcome will have a significant impact on the design principles of biosensors and sensor arrays. The established molecular design principles have been integrated into a graduate course. Two graduate students have been trained through the project. One of them graduated with Ph.D. and has been pursuing an academic career. The other student will graduate with Ph.D. in the winter 2014 term. 6 undergraduate students have actively participated in the research developments and 1 high school student had hands-on research experience from the project. Among them 3 undergraduate students received an authorship in journal publications for their contribution.
