This work focuses on demonstrating proof-of-concept for a novel nanoparticle optical signal amplification scheme employing hybrid porous silicon (PSi) sensors. We are investigating the development of target responsive hydrogels integrated with PSi optical transducers. These hybrid-PSi sensors can be designed to provide a tunable material response to target concentration ranging from swelling to complete chain dissolution. The corresponding refractive index changes are significant and readily detected by the PSi transducer. However, to increase signal to noise, lower the limit of detection, and provide a visual read out capability, we are investigating the incorporation of high refractive index nanoparticles (NP) into the hydrogel for optical signal amplification. These NPs can be nonspecifically encapsulated, or functionalized with bioactive ligands to bind polymer chains or participate in cross linking. In this work, we demonstrate encapsulation of high refractive index QD nanoparticles into a 5wt% polyacrylamide hydrogel crosslinked with N,N'-methylenebisacrylamide (BIS) and N,N Bis-acryloyl cystamine (BAC). A QD loading (~0.29 wt%) produced a 2X larger optical shift compared to the control. Dissolution of disulphide crosslinks, using Tris[2-carboxyethyl] phosphine (TCEP) reducing agent, induced gel swelling and efficient QD release. We believe this hybrid sensor concept constitutes a versatile technology platform capable of detecting a wide range of bio/chemical targets provided target analogs can be linked to the polymer backbone and crosslinks can be achieved with target responsive multivalent receptors, such a antibodies. The optical signal amplification scheme will enable a lower limit of detection sensitivity not yet demonstrated with PSi technology and colorimetric readout visible to the naked eye.
The growing presence of quantum dots (QD) in a variety of biological, medical, and electronics applications means an
increased risk of human exposure in manufacturing, research, and consumer use. However, very few studies have
investigated the susceptibility of skin to penetration of QD - the most common exposure route- and the results of those
that exist are conflicting. This suggests that a technique allowing determination of skin barrier status and prediction of
skin permeability to QD would be of crucial interest as recent findings have provided evidence of in vitro cytotoxicity
and long-term in vivo retention in the body for most QD surface chemistries. Our research focuses on barrier status of the
skin (intact and with ultraviolet radiation induced barrier defect) and its impact on QD skin penetration. These model
studies are particularly relevant to the common application condition of NP containing sunscreen and SPF cosmetics to
UV exposed skin. Herein we present our initial efforts to develop an in vivo model of nanoparticle skin penetration using
the SKH-1 hairless mouse with transepidermal water loss (TEWL) to evaluate skin barrier status and determine its
ability to predict QD penetration. Our results show that ultraviolet radiation increases both TEWL and skin penetration
of QD. Additionally, we demonstrate cytotoxic potential of QD to skin cells using a metastatic melanoma cell line. Our
research suggests future work in specific targeting of nanoparticles, to prevent or enhance penetration. This knowledge
will be used to develop powerful therapeutic agents, decreased penetration cosmetic nanoparticles, and precise skin
cancer imaging modalities.
This work focuses on the development of a proof-of-concept optical sensor design that incorporates an
amine-functionalized polyacrylamide hydrogel into a 1D porous silicon (PSi) photonic crystal. The PSi
acts as both a template and a transducer capable of detecting morphological and dielectric changes in the
incorporated hydrogel structure. Free radical copolymerization of acrylamide (AAm) and N-(3-
aminopropyl)-methacrylamide (NA) monomers was utilized to form copolymer chains with a controlled
concentration of nucleophilic amine moieties. These amine groups facilitated chemical cross-linking of the
copolymer chain to generate hydrogel networks. A molar fraction of >2 mol% of NA monomer was needed
to facilitate a visibly gelatinous hydrogel in a 5 wt% polymer solution. Addition of sodium formate (chain
transfer agent) during copolymer synthesis facilitated decreased copolymer chain length and improved
infiltration of the copolymer into the p-type PSi mesoporous sensor (pore diameters ~20-30 nm).
Controlled cross-linking of the copolymer chains was completed with using glutaraldehyde, as a model
system, to form a hydrogel network that could be optically monitored by the incorporated PSi sensor. These
results lay foundation for extending this versatile methodology towards the design of an affinity based
complimentary target-probe system to create a hybrid target-responsive hydrogel-PSi chemical sensor.
The optical properties of photonic bandgap (PBG) structures are highly sensitive to the geometry and refractive index. This makes PBG structures a good host for sensor applications. The binding of target species inside the PBG structure changes the refractive index of the material, which can be detected by monitoring the optical response of the device. One-dimensional PBG biosensors based on porous silicon (PSi) have been fabricated. The device is a microcavity, made of a symmetry breaking PSi layer (defect layer) inserted between two PSi Bragg mirrors. Narrow resonances are introduced in the photoluminescence and reflectance spectra. The large internal surface of the sensor is functionalized for the capture of target biological materials. When the sensor is exposed to the target, binding to the internal surface increases the effective optical thickness of the microcavity and thus causes a red shift of the optical spectrum. The sensor's sensitivity is determined by the morphology and geometry of the device. We will present the details of the materials science, sensor fabrication and optimization, and also describe experiments performed with biological targets.
High surface area mesoporous silicon microcavities are investigated for direct detect optical biosensor applications. Device quality is reported as a function of fabrication parameters. A dilute KOH etch process is utilized to modify the intrinsic 3D microstructure to enable enhanced pore infiltration of large biomolecules. Results suggest that the KOH etch mechanism is a two step process consisting of a fast step where high surface area nanostructures are rapidly removed. This is followed by a slower step where silicon is removed from the pore channel walls. The enzyme, Glutathione-S-Transferase (50kDa), is utilized to probe pore infiltration. Results from a solid phase immobilized enzyme assay support our conclusions on the impact the KOH etch step has on modifying the porous silicon microstructure. Preliminary findings point to trade-offs that exists between optimizing microstructure with microcavity operation mode and device sensitivity.