Storage and transportation of protein therapeutics using refrigeration is a costly process; a reliable electrical supply is vital, expensive equipment is needed, and unique transportation is required. Reducing the reliance on the cold chain would enable low-cost transportation and storage of biologics, ultimately improving accessibility of this class of therapeutics to patients in remote locations. Herein, we report on the synthesis of charged poly(N-isopropylacrylamide) nanogels that efficiently adsorb a range of different proteins of varying isoelectric points and molecular weights (e.g., adsorption capacity (Q) = 4.7 ± 0.2 mg/mg at 6 mg/mL initial IgG concentration), provide protection from external environmental factors (i.e., temperature), and subsequently release the proteins in an efficient manner (e.g., 100 ± 1% at 2 mg/mL initial IgG concentration). Both cationic and anionic nanogels were synthesized and selectively chosen based on the ability to form electrostatic interactions with adsorbed proteins (e.g., cationic nanogels adsorb low isoelectric point proteins whereas anionic nanogels adsorb high isoelectric point proteins). The nanogel-protein complex formed upon adsorption increases the stabilization of the protein's tertiary structure, providing protection against denaturation at elevated temperatures (e.g., 84 ± 4% of the protected IgG was stabilized when exposed to 65 °C). The addition of a high molar salt solution (e.g., 40 mM CaCl2 solution) to protein-laden nanogels disrupts the electrostatic interactions and collapses the nanogel, ultimately releasing the protein. The versatile materials utilized, in addition to the protein loading and release mechanisms described, provide a simple and efficient strategy to protect fragile biologics for their transport to remote areas without necessitating costly storage equipment.

An athermal approach to mRNA enrichment from total RNA using a self-immolative thioester linked nucleic acids (TENA) is described. Oligo(thymine) (oT) TENA has a six-atom spacing between bases which allowed TENA to selectively base-pair with polyadenine RNA. As a result of the neutral backbone of TENA and the hydrophobicity of the octanethiol end group, oT TENA is water insoluble and efficiently pulled down 93±2 % of EGFP mRNA at a concentration of 10 ng μL . Self-immolative degradation of TENA upon ambient temperature exposure to nucleophilic buffer components (Tris, DTT) allowed recovery of 55±27 ng of mRNA from 3.1 μg of total RNA, which was not statistically different from the amount recovered using Dynabeads® mRNA DIRECT Kit (89±24 ng). Gene expression as measured by RT-qPCR was comparable for both enrichment methods, suggesting that the mild conditions required for enrichment of mRNA using oT TENA are compatible with RT-qPCR and other downstream molecular biology applications.

Enrichment of mRNA is a key step in a number of molecular biology techniques, particularly in the rapidly growing field of transcriptomics. Currently, mRNA is isolated using oligo(thymine) DNA (oligo(dT)) immobilized on solid supports, which binds to the poly(A) tail of mRNA to pull the mRNA out of solution through the use of magnets or centrifugal filters. Here, a simple method to isolate mRNA by complexing it with synthetic click nucleic acids (CNAs) is described. Oligo(T) CNA bound efficiently to mRNA, and because of the insolubility of CNA in water, >90% of mRNA was readily removed from solution using this method. Simple washing, buffer exchange, and heating steps enabled mRNA's enrichment from total RNA, with a yield of 3.1 ± 1.5% of the input total RNA by mass, comparable to the yield from commercially available mRNA enrichment beads. Further, the integrity and activity of mRNA after CNA-facilitated pulldown and release was evaluated through two assays. In vitro translation of EGFP mRNA confirmed the translatability of mRNA into functional protein and RT-qPCR was used to amplify enriched mRNA from total RNA extracts and compare gene expression to results obtained using commercially available products.

This chapter explores polymers that are capable of degrading to smaller components under physiologically relevant conditions or upon exposure to specific stimuli. Such polymers have been used in a wide range of biomaterials, spanning from sutures to drug delivery devices to orthopedic implants. Key definitions and concepts relating to biodegradation and resorption are explained, after which more details on different classes of degradable polymers are discussed. The properties of such polymers that affect their degradation are detailed to give readers a better understanding of the tunability of biodegradation. While this chapter largely focuses on hydrolytically degradable polymers and the kinetics of hydrolytic degradation, polymers that are degraded by other stimuli (e.g., enzymes, light) are also highlighted. Beyond the polymer structure, the effects of processing on degradation are discussed to emphasize the many different considerations that must be taken into account when designing a new degradable biomaterial. Several worked examples and case studies are provided to reinforce concepts relating to biodegradable and resorbable polymers.

Click nucleic acids (CNAs) are a new, low-cost class of xeno nucleic acid (XNA) oligonucleotides synthesized by an efficient and scalable thiol-ene polymerization. In this work, a thorough characterization of oligo(thymine) CNA-oligo(adenine) DNA ((dA)(20)) hybridization was performed to guide the future implementation of CNAs in applications that rely on sequence-specific interactions. Microscale thermophoresis provided a convenient platform to rapidly and systematically investigate the effects of several factors (i.e., sequence, length, and salt concentration) on the CNA-DNA dissociation constant (K-app). Because CNAs have limited water solubility, all studies were performed in aqueous-DMSO mixtures. CNA-DNA hybrids between oligo(thymine) CNA (average length of 16 bases) and (dA)(20) DNA have good stability despite the high organic content, a favorable attribute for many emerging applications of XNAs. In particular, the K-app of CNA-DNA hybrids in 65 vol % DMSO with 10 mM sodium chloride (NaCl) was 0.74 +/- 0.1 mu M, whereas the K-app for (dT)(20)-(dA)(20) DNA-DNA was found to be 45 +/- 2 mu M in a buffer without DMSO but at the same NaCl concentration. CNA hybridized with DNA following Watson-Crick base pairing with excellent sequence specificity, discriminating even a single-base-pair mismatch, with K-app values of 0.74 +/- 0.1 and 3.7 +/- 0.6 mu M for complementary and single-base-pair mismatch sequences, respectively. As with dsDNA, increasing CNA length led to more stable hybrids as a result of increased base pairing, where K-app decreased from 5.6 +/- 0.8 to 0.27 +/- 0.1 mu M as the CNA average length increased from 7 to 21 bases. However, unlike DNA-DNA duplexes, which are largely unstable at low salt concentrations, the CNA-DNA stability does not depend on salt concentration, with K-app remaining consistent between 1.0 and1.9 mu M over a NaCl concentration range of 1.25-30 mM.

Efficient intracellular delivery of biomacromolecules such as proteins continues to remain a challenge despite its potential for medicine. In this work, we show that mScarlet, a non cytotoxic red fluorescent protein (RFP) conjugated to Click Nucleic Acid (CNA), a synthetic analog of DNA, undergo cell uptake significantly more than either native proteins or proteins conjugated with similar amounts of DNA in MDA-MB-468 cells. We further demonstrate that the process of cell uptake is metabolically driven and that scavenger receptors and caveolae mediated endocytosis play a significant role. Co-localization studies using anti-scavenger receptor antibodies suggest that scavenger receptors are implicated in the mechanism of uptake of CNA modified proteins.

Beyond their central role in storing and transmitting genetic information, nucleic acids are renowned for their high-specificity, high-affinity hybridization. In the past several decades, scientists have become increasingly interested in emulating this unique property of nucleic acids using syntheticmimics. Many creative strategies for the synthesis of xenonucleic acids (XNAs) have been developed, with the field ultimately striving for high-efficiency, scalable routes to achieving sequence-controlled XNA synthesis. Emerging strategies in both biology (e.g., directed evolution) and chemistry (e.g., dynamic covalent reactions) are leading to new breakthroughs in XNA synthesis that will make applications of nucleic acids, such as gene therapy, agricultural disease management, and electronics, more accessible.

An approach to efficient and scalable production of oligonucleotide-based gel networks is presented. Specifically, a new class of xenonucleic acid (XNA) synthesized through a scalable and efficient thiol-ene polymerization mechanism, "Clickable" Nucleic Acids (CNAs), were conjugated to a multifunctional poly(ethylene glycol), PEG. In the presence of complementary single stranded DNA (ssDNA), the macromolecular conjugate assembled into a crosslinked 3D gel capable of achieving storage moduli on the order of 1 kPa. Binding studies between the PEG-CNA macromolecule and complementary ssDNA indicate that crosslinking is due to the CNA/DNA interaction. Gel formation was specific to the base sequence and length of the ssDNA crosslinker. The gels were fully thermoreversible, completely melting at temperatures above 60°C and re-forming upon cooling over multiple cycles and with no apparent hysteresis. Shear stress relaxation experiments revealed that relaxation dynamics are dependent on crosslinker length, which is hypothesized to be an effect of the polydisperse CNA chains. Arrhenius analysis of characteristic relaxation times was only possible for shorter crosslinker lengths, and the activation energy for these gels was determined to be 110 ± 20 kJ/mol. Overall, the present work demonstrates that CNA is capable of participating in stimuli-responsive interactions that would be expected from XNAs, and that these interactions support 3D gels that have potential uses in biological and materials science applications.

A phosphatidylcholine-based cerasome (PC-cerasome) was prepared by a combination of a copper-catalyzed azide alkyne cyclo-addition (CuAAC) reaction and a sol-gel condensation process. In a 2 wt % urea aqueous solution, azide precursors containing a triethoxysilane group (TEOS) were coupled with an alkyne lysolipid (AL) through a CuAAC reaction to generate triethoxysilane triazole-phosphatidylcholine (TEOSTPC) molecules. TEOSTPC self-assembled into liposomes immediately after formation. Incubation of the liposomes at 50 degrees C led to a gradual hydrolysis and decomposition of urea, which caused a mildly basic condition. Simultaneously, a base-catalyzed sol-gel condensation of TEOS groups occurred and drove formation of a silica network in the bilayer membranes of the TEOSTPC-liposomes, resulting in cerasomes with an organic/inorganic hybrid shell composed of PC and an SO2 network. Because of the presence of the SO2 network in the bilayer membrane, the cerasomes exhibited good structural stability in the aqueous phase and maintained the vesicular structure even when dispersed in water-miscible organic solvents. Coexistence of the bilayer membrane and SiO2 was verified, which is indicative of an intramembrane sol-gel condensation. The formation process of an SiO2 network in the bilayer membrane was verified using spiropyran-containing triazole-phosphatidylcholine (SPTPC) as a molecular probe. The SPTPC was embedded in TEOSTPC-liposomes, and subsequent sol-gel condensation anchored the SPTPCs in the SiO2 network. During sol-gel condensation, SP isomerized to merocyanine (MC), indicating that the polarity of the microenvironment in the bilayer membrane increased due to formation of the SiO2 network. Moreover, the rigidity of the SiO2 network prohibited MC-to-SP recovery, resulting in a cerasome with a MC-functionalized shell. Based on the structural stability of the PC-cerasome and the convenient preparation method combining CuAAC and sol-gel condensation, we anticipate that these PC-cerasomes will find broad utility in the construction of vesicular materials with functionalized shells.

A spiropyran-containing triazole-phosphatidylcholine (SPTPC) was synthesized through a copper-catalyzed azide alkyne cyclo-addition (CuAAC) reaction. In water, SPTPCs self-assembled and a spontaneous spiropyran-to-merocyanine (SP-to-MC) isomerization occurred, resulting in coexistence of liposomes and fibers, and switching from the spiropyran (SP) to the merocyanine (MC) isomeric structure induced a reversible transition between these molecular assemblies. Study of the self-assembly of SPTPCs and photo-induced liposome-fiber assembly-transition revealed that the presence of MC enabled additional inter-membrane interaction during self-assembly and that the MC-stacking effect was the driving force for the assembly-transition. Exposure to UV light induced switching from SP to MC, where the planar structure of MC and the confinement of MC led to enhanced MC-stacking. The effect of MC-stacking was both advantageous and disadvantageous: MC-stacking perturbed the hydrophobic phase in the bilayer membrane and facilitated the liposome-to-fiber transition, otherwise the MC-stacking retarded switching of MC to SP, and caused an incomplete recovery of MC to SP during fiber-to-liposome recovery, thus a fatigue of SP was induced by MC-stacking during the liposome-to-fiber transition cycle. To decrease the intermolecular interactions and suppress MC-stacking, photo-inert triazole-phosphatidylcholine (TPC) was incorporated to prepare two-component TPC/SPTPC-liposomes, which exhibited better recovery kinetics. The photo-adaptive behavior of TPC/SPTPC-liposomes confirmed the disturbance of bilayer membranes by inter-membrane MC-stacking and the formation of MCTPC-enriched phases in the bilayer membrane.

The synthesis of thiolactone monomers that mimic natural nucleosides and engage in robust ring opening polymerizations (ROP) is herein described. As each repeat unit contains a thioester functional group, dynamic rearrangement of the polymer is feasible via thiol-thioester exchange, demonstrated here by depolymerization of the polymers and coalescing of two polymers of different molecular weight or chemical composition. This approach constitutes the first step toward a platform that enables for the routine synthesis of sequence controlled polymers via dynamic template directed synthesis.

Due to the ability to generate oligomers of precise sequence, sequential and stepwise solid-phase synthesis has been the dominant method of producing DNA and other oligonucleotide analogues. The requirement for a solid support, however, and the physical restrictions of limited surface area thereon significantly diminish the efficiency and scalability of these syntheses, thus, negatively affecting the practical applications of synthetic polynucleotides and other similarly created molecules. By employing the robust photoinitiated thiol-ene click reaction, we developed a new generation of clickable nucleic acids (CNAs) with a polythioether backbone containing repeat units of six atoms, matching the spacing of the phosphodiester backbone of natural DNA. A simple, inexpensive, and scalable route was utilized to produce CNA monomers in gram-scale, which indicates the potential to dramatically lower the cost of these DNA mimics and thereby expand the scope of these materials. The efficiency of this approach was demonstrated by the completion of CNA polymerization in 30 seconds, as characterized by size-exclusive chromatography (SEC) and infrared (IR) spectroscopy. CNA/DNA hybridization was demonstrated by gel electrophoresis and used in CdS nanoparticle assembly.

The dependence of the localized surface plasmon resonance (LSPR) of noble-metal nanomaterials on refractive index makes LSPR a useful, label-free signal transduction strategy for biosensing. In particular, by decorating gold nanomaterials with molecular recognition agents, analytes of interest can be trapped near the surface, resulting in an increased refractive index surrounding the nanomaterial, and, consequently, a red shift in the LSPR wavelength. Ionic poly( N-isopropylacrylamide- co-methacrylic acid) (PNM) hydrogels were used as protein receptors because PNM nanogels exhibit a large increase in refractive index upon protein binding. Specifically, PNM hydrogels were synthesized on the surface of silica gold nanoshells (AuNSs). This composite material (AuNS@PNM) was used to detect changes in the concentration of two protein biomarkers of chronic dry eye: lysozyme and lactoferrin. Both of these proteins have high isoelectric points, resulting in electrostatic attraction between the negatively charged PNM hydrogels and positively charged proteins. Upon binding lysozyme or lactoferrin, AuNS@PNM exhibits large, concentration-dependent red shifts in LSPR wavelength, which enabled the detection of clinically relevant concentration changes of both biomarkers in human tears. The LSPR-based biosensor described herein has potential utility as an affordable screening tool for chronic dry eye and associated conditions.

Nature has mastered the art of molecular recognition. For example, using synergistic non-covalent interactions, proteins can distinguish between molecules and bind a partner with incredible affinity and specificity. Scientists have developed, and continue to develop, techniques to investigate and better understand molecular recognition. As a consequence, analyte-responsive hydrogels that mimic these recognitive processes have emerged as a class of intelligent materials. These materials are unique not only in the type of analyte to which they respond but also in how molecular recognition is achieved and how the hydrogel responds to the analyte. Traditional intelligent hydrogels can respond to environmental cues such as pH, temperature, and ionic strength. The functional monomers used to make these hydrogels can be varied to achieve responsive behavior. For analyte-responsive hydrogels, molecular recognition can also be achieved by incorporating biomolecules with inherent molecular recognition properties (e.g., nucleic acids, peptides, enzymes, etc.) into the polymer network. Furthermore, in addition to typical swelling/syneresis responses, these materials exhibit unique responsive behaviors, such as gel assembly or disassembly, upon interaction with the target analyte. With the diverse tools available for molecular recognition and the ability to generate unique responsive behaviors, analyte-responsive hydrogels have found great utility in a wide range of applications. In this Account, we discuss strategies for making four different classes of analyte-responsive hydrogels, specifically, non-imprinted, molecularly imprinted, biomolecule-containing, and enzymatically responsive hydrogels. Then we explore how these materials have been incorporated into sensors and drug delivery systems, highlighting examples that demonstrate the versatility of these materials. For example, in addition to the molecular recognition properties of analyte-responsive hydrogels, the physicochemical changes that are induced upon analyte binding can be exploited to generate a detectable signal for sensing applications. As research in this area has grown, a number of creative approaches for improving the selectivity and sensitivity (i.e., detection limit) of these sensors have emerged. For applications in drug delivery systems, therapeutic release can be triggered by competitive molecular interactions or physicochemical changes in the network. Additionally, including degradable units within the network can enable sustained and responsive therapeutic release. Several exciting examples exploiting the analyte-responsive behavior of hydrogels for the treatment of cancer, diabetes, and irritable bowel syndrome are discussed in detail. We expect that creative and combinatorial approaches used in the design of analyte-responsive hydrogels will continue to yield materials with great potential in the fields of sensing and drug delivery.

Due to the high cost and environmental instability of antibodies, there is precedent for developing synthetic molecular recognition agents for use in diagnostic sensors. While these materials typically have lower specificity than antibodies, their cross-reactivity makes them excellent candidates for use in differential sensing routines. In the current work, we design a set of charge-containing poly(N-isopropylacrylamide) (PNIPAM) nanogels for use as differential protein receptors in a turbidimetric sensor array. Specifically, NIPAM was copolymerized with methacrylic acid and modified via carbodiimide coupling to introduce sulfate, guanidinium, secondary amine, or primary amine groups. Modification of the ionizable groups in the network changed the physicochemical and protein binding properties of the nanogels. For high affinity protein-polymer interactions, turbidity of the nanogel solution increased, while for low affinity interactions minimal change in turbidity was observed. Thus, relative turbidity was used as input for multivariate analysis. Turbidimetric assays were performed in two buffers of different pH (i.e., 7.4 and 5.5), but comparable ionic strength, in order to improve differentiation. Using both buffers, it was possible to achieve 100% classification accuracy of eleven model protein biomarkers with as few as two of the nanogel receptors. Additionally, it was possible to detect changes in lysozyme concentration in a simulated tear fluid using the turbidimetric sensor array.

The potential to develop materials with antibody-like molecular recognition properties has helped sustain interest in protein-imprinted polymers over the past several decades. Unfortunately, despite persistent research, the field of noncovalent protein imprinting has seen limited success in terms of achieving materials with high selectivity and high affinity. In this Perspective, important yet sometimes overlooked aspects of the imprinting and binding processes are reviewed to help understand why there has been limited success. In particular, the imprinting and binding processes are viewed through the scope of free radical polymerization and hydrogel swelling theories to underscore the complexity of the synthesis and behavior of protein-imprinted polymers. Additionally, we review the metrics of success commonly used in protein imprinting literature (i.e., adsorption capacity, imprinting factor, and selectivity factor) and consider the relevance of each to the characterization of an imprinted polymer's recognition characteristics. Throughout, common shortcomings are highlighted, and experiments that could help verify or disprove the efficacy of noncovalent protein imprinting are discussed.

Molecularly imprinted polymers (MIPs) are often investigated as lower cost, more environmentally robust alternatives to natural recognitive biomolecules, such as antibodies. When synthesized on the surface of nanomaterial supports, MIPs are capable of quick and effective binding of macromolecular templates when compared to traditional bulk-imprinted polymers. We have developed a method for imprinting proteins on biodegradable nanoparticle supports and have used these materials to investigate the impact of molecular imprinting on adsorption capacity and selectivity for lysozyme, the template protein. The imprinting process increased the adsorption capacity of the polymer for the template, lysozyme, with the MIPs being able to bind up to 83.5% of their dry weight as compared to 55.7% for nonimprinted polymers (NIPs). In noncompetitive binding experiments, where proteins were independently incubated with MIPs, the difference between adsorption capacity for lysozyme and proteins with much lower isoelectric points (pI < 8.0) was statistically significant. However, there was no statistical difference between adsorption capacity for lysozyme and other high-isoelectric point proteins, suggesting that MIPs are semiselective for this class of proteins. In competitive binding experiments, both MIPs and NIPs preferentially bound lysozyme over other high-isoelectric point proteins. This result demonstrated that imprinting alone could not account for the observed selectivity for lysozyme. Analysis of the solvent accessible surface area of lysozyme and its high-isoelectric point competitors revealed why lysozyme is an exceptional binder to the polymer system used in this work, with or without imprinting.

Event Abstract Back to Event Development of protein biosensors using surface-imprinted silica-gold nanoshells Heidi R. Culver1, 2, Laura E. Strong1, 2 and Nicholas A. Peppas1, 2, 3, 4 1 University of Texas at Austin, Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, United States 2 University of Texas at Austin, Biomedical Engineering, United States 3 University of Texas at Austin, Chemical Engineering, United States 4 University of Texas at Austin, Pharmacy, United States Introduction: Molecularly imprinted polymers (MIPs) are synthetic materials engineered to recognize specific molecules. MIPs are promising alternatives to antibodies in the development of biosensors because they are less expensive and more environmentally robust. Furthermore, MIPs can be synthesized on the surface of nanomaterials to develop receptors with built-in signal transduction properties[1]-[3]. For example, the localized surface plasmon resonance (LSPR) of noble metal nanomaterials, which is sensitive to changes in local refractive index, can be exploited to detect molecular binding events near their surfaces. In particular, nanomaterials with high aspect ratios, such as gold nanoshells grown from silver or silica nanoparticles, have enhanced LSPR sensitivity to changes in refractive index compared to colloidal gold[4]. In the current work, we synthesize MIPs on the surface of silica-gold nanoshells (AuNSs) and take advantage of their enhanced LSPR sensitivity to selectively detect lysozyme (Lys). Materials and Methods: AuNSs were synthesized as previously described[5] and then capped with 1-dodecanethiol. Hydrophobically modified AuNSs were encapsulated in poly(maleic anhydride-alt-1-octadecene)-grafted-poly(ethylene glycol) methacrylate (PMAO-g-PEGMA) via solvent displacement. AuNSs and Lys were combined with N-isopropylacrylamide, methacrylic acid, and N,N’-methylene bisacrylamide to pre-assemble under nitrogen before initiating polymerization with APS/TEMED. Following Lys removal and purification, AuNSs were incubated with Lys and two other non-template proteins, cytochrome c (Cyt c) and bovine serum albumin (BSA). Absorbance spectra were measured to detect LSPR response to increasing protein concentrations. Results and Discussion: Gold nanoshell growth, encapsulation in PMAO-g-PEGMA, and MIP growth were characterized by dynamic light scattering (Figure 1A) and transmission electron microscopy (Figure 1B,C). Encapsulation in PMAO-g-PEGMA resulted in colloidally stable AuNSs with reactive methacrylate groups that were used to link Lys MIPs to their surfaces (AuNS@Lys-MIPs). Bare AuNSs and AuNSs encapsulated in PMAO-g-PEGMA showed negligible LSPR shifts upon incubation with Lys, Cyt c, and BSA. However, for AuNS@Lys-MIPs, there was a clear red-shift in the LSPR wavelength upon incubation with increasing concentrations of Lys (Figure 2A). LSPR shifts observed for BSA and Cyt c were negligible (<10 nm) and there was no correlation between concentration and LSPR shift for either non-template protein, suggesting that Lys-MIPs are selective for Lys (Figure 2B). Conclusion: We have used surface modified AuNSs to grow MIP shells and have demonstrated that binding interactions between AuNS@Lys-MIPs and Lys cause large LSPR shifts that are not observed for non-template proteins. These imprinted AuNSs combine molecular recognition and signal transduction properties in a single entity, making them a useful tool for biosensing applications. References:[1] Cai, D., Ren, L., Zhao, H., Xu, C., Zhang, L., Yu, Y., Wang, H., Lan, Y., Roberts, M. F., Chuang, J. H., Naughton, M. J., Ren, Z. & Chiles, T. C. A molecular-imprint nanosensor for ultrasensitive detection of proteins. Nat. Nanotechnol. 5, 597–601 (2013).[2] Abbas, A., Tian, L., Morrissey, J. J., Kharasch, E. D. & Singamaneni, S. Hot Spot-Localized Artificial Antibodies for Label-Free Plasmonic Biosensing. Adv. Funct. Mater. 23, 1789–1797 (2013).[3] Tan, L., Kang, C., Xu, S., & Tang, Y. Selective room-temperature phosphorescence sensing of target protein using Mn-doped ZnS QDs-embedded molecularly imprinted polymer. Biosens. Bioelectron. 48, 216-233 (2013).[4] Sun, Y. & Xia, Y. Increased Sensitivity of Surface Plasmon Resonance of Gold Nanoshells Compared to That of Gold Solid Colloids in Response to Environmental Changes. Anal. Chem. 74, 5297–5305 (2002).[5] Oldenburg, S. J., Averitt, R. D., Westcott, S. L. & Halas, N. J. Nanoengineering of optical resonances. Chem. Phys. Lett. 288, 243–247 (1998). Keywords: biosensing, nanoparticle, protein, Surface modification Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Molecular imprinting on surfaces Citation: Culver HR, Strong LE and Peppas NA (2016). Development of protein biosensors using surface-imprinted silica-gold nanoshells. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00185 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Heidi R Culver Laura E Strong Nicholas A Peppas Google Heidi R Culver Laura E Strong Nicholas A Peppas Google Scholar Heidi R Culver Laura E Strong Nicholas A Peppas PubMed Heidi R Culver Laura E Strong Nicholas A Peppas Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.