Andrew David Pris

Theoretical limit of localized surface plasmon resonance sensitivity to local refractive index change and its comparison to conventional surface plasmon resonance sensor.

In this paper, the theoretical sensitivity limit of the localized surface plasmon resonance (LSPR) to the surrounding dielectric environment is discussed. The presented theoretical analysis of the LSPR phenomenon is based on perturbation theory. Derived results can be further simplified assuming quasistatic limit. The developed theory shows that LSPR has a detection capability limit independent of the particle shape or arrangement. For a given structure, sensitivity is directly proportional to the resonance wavelength and depends on the fraction of the electromagnetic energy confined within the sensing volume. This fraction is always less than unity; therefore, one should not expect to find an optimized nanofeature geometry with a dramatic increase in sensitivity at a given wavelength. All theoretical results are supported by finite-difference time-domain calculations for gold nanoparticles of different geometries (rings, split rings, paired rings, and ring sandwiches). Numerical sensitivity calculations based on the shift of the extinction peak are in good agreement with values estimated by perturbation theory. Numerical analysis shows that, for thin (≤10 nm) analyte layers, sensitivity of the LSPR is comparable with a traditional surface plasmon resonance sensor and LSPR has the potential to be significantly less sensitive to temperature fluctuations.

Emerging Understanding of Multiscale Tumor Heterogeneity

Cancer is a multifaceted disease characterized by heterogeneous genetic alterations and cellular metabolism, at the organ, tissue, and cellular level. Key features of cancer heterogeneity are summarized by 10 acquired capabilities, which govern malignant transformation and progression of invasive tumors. The relative contribution of these hallmark features to the disease process varies between cancers. At the DNA and cellular level, germ-line and somatic gene mutations are found across all cancer types, causing abnormal protein production, cell behavior, and growth. The tumor microenvironment and its individual components (immune cells, fibroblasts, collagen, and blood vessels) can also facilitate or restrict tumor growth and metastasis. Oncology research is currently in the midst of a tremendous surge of comprehension of these disease mechanisms. This will lead not only to novel drug targets but also to new challenges in drug discovery. Integrated, multi-omic, multiplexed technologies are essential tools in the quest to understand all of the various cellular changes involved in tumorigenesis. This review examines features of cancer heterogeneity and discusses how multiplexed technologies can facilitate a more comprehensive understanding of these features.

Towards Maintenance-Free Biosensors for Hundreds of Bind/Release Cycles†

A single aptamer bioreceptor layer was formed using a common streptavidin-biotin immobilization strategy and employed for 100-365 bind/release cycles. Chemically induced aptamer unfolding and release of its bound target was accomplished using alkaline solutions with high salt concentrations or deionized (DI) water. The use of DI water scavenged from the ambient atmosphere represents a first step towards maintenance-free biosensors that do not require the storage of liquid reagents. The aptamer binding affinity was determined by surface plasmon resonance and found to be almost constant over 100-365 bind/release cycles with a variation of less than 5% relative standard deviation. This reversible operation of biosensors based on immobilized aptamers without storage of liquid reagents introduces a conceptually new perspective in biosensing. Such new biosensing capability will be important for distributed sensor networks, sensors in resource-limited settings, and wearable sensor applications.

Immobilization of aptamers onto unmodified glass surfaces for affordable biosensors

Silicon dioxide surfaces are commonly used in photonic microsensors for bioreceptor attachment. Functionalization of sensor surface with aptamer receptors provides the opportunity to develop low cost, robust, field deployable sensors. Most aptamer sensors are constructed by covalently linking modified aptamers to a derivatized surface. There have been reports of using UV crosslinking to directly immobilize DNA with sequences that end with poly(T)10-poly(C)10 on an unmodified glass surface for hybridization. We have expanded this strategy using thrombin-binding aptamers (TBAs) with three different tail modifications. TBA with PolyT20 tail showed the best performance in terms of sensitivity and dynamic range. PolyTC tailed aptamers did not bind thrombin well, which may be due to that the interactions between the C bases and G-quadruplex affect their target binding capability. When compared to biotinylated aptamer immobilized on a streptavidin surface, polyT aptamer printed directly on plain glass showed comparable affinity. Direct immobilization of TBA on nonfunctionalized silicon dioxide wafer and its binding towards thrombin has also been demonstrated. Our results showed that using polyT-tagged aptamer probes directly immobilized on unmodified glass and SiO2 surface is a robust, very straightforward, and inexpensive method for preparing biosensors.

Theoretical and experimental development of label-free biosensors based on localized plasmon resonances on nanohole and nanopillar arrays

Development of localized surface plasmon resonance (LSPR) sensors for label-free biodetection draws considerable attention because of the potential of these sensors to provide simplified detection schemes, improved detection limits, and high-density multiplexed array configurations. In this paper, we present our recent results on the theoretical and experimental development of LSPR label-free biosensors based on nanohole and nanopillar arrays. First, we theoretically compare the analytical performance metrics of wavelength modulated SPR and LSPR platforms for biological recognition with surface-immobilized bioreceptors (e.g. antibodies and aptamers). Further, we discuss our results on the application of a focused ion beam (FIB) technique to fabricate arrays of nanoholes and nanopillars in Au films, investigate the origin and type of FIB-induced surface contamination, and demonstrate an efficient way for its elimination. Next, we evaluate the refractive index (RI) response sensitivity of FIB-fabricated arrays of nanoholes (443 - 513 nm/RIU) and nanopillars (423 nm/RIU) in Au films. Further, we demonstrate the opportunities that are available from the multivariate spectral analysis of plasmonic nanostructures for improvement of sensor system performance. Finally, we present typical simulation results of predicting RI sensitivity of plasmonic nanostructures using finite-difference time-domain technique (FDTD) and discuss the remaining challenges of simulation techniques for design of LSPR sensors.