Porous silicon (PSi) thin films on silicon substrates have been extensively investigated in the context of biosensing applications, particularly for achieving label-free optical detection of a wide range of analytes. However, mass transport challenges have made it difficult for these biosensors to achieve rapid response times and low detection limits. In this work, we introduce an approach for improving the efficiency of molecule transport in PSi by using open-ended PSi membranes atop paper substrates in a flow-through sensor scheme. The paper substrate provides structural support as well as an efficient means of draining solutions from the PSi membrane without the use of an external pump and microfluidic channels. Distinct changes in the reflectance properties of the PSi membrane are measured when molecules are captured in the membrane. A concentration-dependent response of the sensor for protein detection is demonstrated. Factors influencing the interaction time of molecules in the PSi membrane and the drying time of the membrane, which directly affect the detection sensitivity and overall testing time, are discussed. The demonstrated performance of the PSi-on-paper sensor establishes the feasibility of a platform for low-cost rapid diagnostic tests with a highly sensitive, quantitative readout.

Porous silicon (PSi)-based biosensors are a promising platform for quantitative rapid diagnostics, but they have not broadly realized clinically relevant limits of detection due, in part, to poor baseline stability. Baseline instability can be attributed to two major physicochemical challengeshydrolysis of PSi in aqueous solutions and fouling by unwanted biological species, both of which can obscure the detection of target molecules at low concentrations. In this work, PSi was thermally hydrosilated with vinylbenzyl chloride (VBC) to incorporate hydrolytically stable Si-C bonding and to provide an attached alkyl halide termination for further chemistry. Subsequent grafting of zwitterionic poly-(sulfobetaine methacrylate) (SBMA) from this PSi-VBC layer by surface-initiated atom-transfer radical polymerization (siATRP) formed an antifouling coating. Films both with and without the antifouling polymer were exposed to PBS (pH 7.4) and human blood serum, and optical reflectance measurements were used to monitor hydrolysis and nonspecific adsorption. PSi-VBC-polySBMA surfaces exhibited little to no nonspecific binding, as determined by ATR-FTIR and optical reflectance measurements, due to their hydrophilicity. The compatibility of hydrosilylation and siATRP with various chemical groups provides significant versatility in this surface chemistry approach, as well as facilitates the incorporation of highly specific capture agents. By directly addressing the issues of hydrolysis and fouling, this strategy holds promise for reducing the limits of detection in complex biological samples.

A paper-based biosensor integrating a functionalized porous silicon (PSi) membrane as the active sensing element for quantifiable protein detection has been developed. For similar short-time exposures to an analyte, improved molecular transport in PSi membranes when on paper leads to larger signal changes compared to traditional PSi films that remain on a silicon substrate. In this work, we discuss controlling the incubation time of the analyte and the overall testing time of the sensor by incorporating different combinations of wicking and absorbent paper beneath the PSi membrane. With this control, the PSi-on-paper sensor platform has the potential to serve as an effective low-cost rapid diagnostic test with highly sensitive, quantitative readout for a wide range of analytes.

We report the incorporation of porous silicon on paper towards the realization of a low-cost rapid diagnostic testing platform with the capability for quantification of detected molecules. Real-time optical reflectance measurements of bovine serum albumin adsorption were carried out to benchmark the sensor. Simulations and experiments demonstrate a response-time dependence on porous silicon pore size. Approaches to overcome challenges with porous silicon adhesion on paper and porous silicon membrane mechanical robustness will be discussed.

We demonstrate detection of the malaria biomarker PfHRP2 using a porous silicon (PSi) optical biosensor. Specificity was achieved with anti-PFHRP2 antibodies "clicked" to an azide-containing polymeric film grafted from the PSi surface. This work showcases the potential of PSi biosensors for clinically relevant diagnostics.

We present a new route for obtaining surface-tethered polymer films containing pendant catechol functional groups via surface-initiated activators regenerated by electron-transfer atom-transfer radical polymerization (SI-ARGET ATRP) of glycidyl methacrylate (GMA) and post-polymerization modification of the resulting poly(glycidyl methacrylate) (pGMA) films with dopamine. This method enables a high degree of functionalization of pGMA films with catechol groups at a controlled level, depending on the duration of the post-polymerization modification reaction. The dopamine-pGMA films readily absorbs Al3+ and Zn2+ ions, as verified by quartz crystal microbalance with dissipation (QCM-D) under continuous flow conditions, and demonstrates a four-fold molar selectivity to Al3+ over Zn2+. The ions desorb from the films upon rinsing with pure deionized (DI) water, which regenerates the catechol sites in the dopamine-pGMA film. Subsequent exposure to metal ions after rinsing steps yields reproducible levels of loading.

The detection of pathogens presents specific challenges in ensuring that biosensors remain operable despite exposure to elevated temperatures or other extreme conditions. The most vulnerable component of a biosensor is typically the bioreceptor. Accordingly, the robustness of peptides as bioreceptors offers improved stability and reliability toward harsh environments compared to monoclonal antibodies that may lose their ability to bind target molecules after such exposures. Here, we demonstrate peptide-based capture of the Chikungunya virus E2 protein in a porous silicon microcavity biosensor at room temperature and after exposure of the peptide-functionalized biosensor to high temperature. Contact angle measurements, attenuated total reflectance—Fourier transform infrared spectra, and optical reflectance measurements confirm peptide functionalization and selective E2 protein capture. This work opens the door for other pathogenic biomarker detection using peptide-based capture agents on porous silicon and other surface-based sensor platforms.

We report the use of a peptide-based capture agent as an alternative to antibodies and nucleic acid-based bioreceptors for porous silicon biosensors. Click chemistry is employed to attach azide-functionalized streptavidin-binding peptides to alkyne-modified porous silicon films. The attachment of the streptavidin-binding peptide and subsequent detection of streptavidin molecules are verified using optical reflectance and Fourier transform infrared spectroscopy measurements.

In this work, thermal carbonization is shown to provide the necessary surface passivation to enable highly robust DNA detection on a porous silicon (PSi) platform, overcoming previous corrosion challenges with detection of negatively charged biomolecules. The stability of thermally carbonized PSi (TCPSi), oxidized PSi (OPSi), and undecylenic acid-modified PSi (UAPSi) is compared in phosphate-buffered saline and during DNA sensing experiments. Reflectance measurements reveal an improvement in stability and DNA sensor response for TCPSi compared to OPSi and UAPSi. TCPSi exhibits a large positive sensor response with >90% DNA hybridization efficiency. In comparison, UAPSi shows a smaller positive DNA sensor response, likely lessened by a small corrosion effect, while OPSi exhibits a large negative sensor response, indicating significant induced PSi corrosion that confounds the ability of OPSi to yield meaningful readouts of DNA hybridization events. This work expands the application of TCPSi for its more widespread usage in sensing applications where competing substrate corrosion may influence device stability.

This manuscript details a novel and simple approach to achieve surface-tethered co-poly(ionic liquid) (coPIL) films through the exchange of the resident anion of a poly(ionic liquid) (PIL) film with two or more anions. Initially, surface-tethered PIL films were prepared by the surface-initiated ring-opening metathesis polymerization of the ionic liquid monomer 3-[(bicyclo[2.2.1]hept-5-en-2-yl)methyl]-1,2-dimethylimidazol-3-ium hexafluorophosphate ([N1-dMIm][PF6]) whose PF6- anion was easily interchanged with aqueous solutions containing a binary mixture of the PF6- anion, along with perchlorate (ClO4-) or bis(fluorosulfonyl)imide (FSI-) anions. The binary mole fraction of each anion in the film was determined from the infrared spectra of the coPIL films. The thermodynamically driven anion selectivity for exchange from the liquid phase into the coPIL films was determined to follow the order ClO4- < PF6- < FSI-. The aqueous wettability of p[N1-dMIm] coPIL films containing both the PF6- and ClO4- anions (p[N1-dMIm][PF6][ClO4]) was quantified by contact angle goniometry with the observation that the surface showed an enrichment in the ClO4- anion compared to the average binary anion mole fraction of ClO4- in the film (yClO4- ). The rate of ion transport through the p[N1-dMIm][PF6][ClO4] coPIL films, quantified by electrochemical impedance spectroscopy, linearly depends on the binary anion mole fraction of ClO4- in solution (xClO4- ), enabling continuous tunability by over three orders of magnitude for ion conductivity in the coPIL films.

Spatial resolution is a key parameter in imaging mass spectrometry (IMS). Aside from being a primary determinant in overall image quality, spatial resolution has important consequences on the acquisition time of the IMS experiment and the resulting file size. Hardware and software modifications during instrumentation development can dramatically affect the spatial resolution achievable using a given imaging mass spectrometer. As such, an accurate and objective method to determine the working spatial resolution is needed to guide instrument development and ensure quality IMS results. We have used lithographic and self-assembly techniques to fabricate a pattern of crystal violet as a standard reticle slide for assessing spatial resolution in matrix-assisted laser desorption/ionization (MALDI) IMS experiments. The reticle is used to evaluate spatial resolution under user-defined instrumental conditions. Edgespread analysis measures the beam diameter for a Gaussian profile and line scans measure an "effective" spatial resolution that is a convolution of beam optics and sampling frequency. The patterned crystal violet reticle was also used to diagnose issues with IMS instrumentation such as intermittent losses of pixel data.

A flow-through sensing platform based on open-ended porous silicon (PSi) microcavity membranes that are compatible with integration in on chip sensor arrays is demonstrated. Because of the high aspect ratio of PSi nanopores, the performance of closed-ended PSi sensors is limited by infiltration challenges and slow sensor responses when detecting large molecules such as proteins and nucleic acids. In order to improve molecule transport efficiency and reduce sensor response time, open-ended PSi nanopore membranes were used in a flow-through sensing scheme, allowing analyte solutions to pass through the nanopores. The molecular binding kinetics in these PSi membranes were compared through experiments and simulation with those from closed-ended PSi films of comparable thickness in a conventional flow-over sensing scheme. The flow-through PSi membrane resulted in a 6-fold improvement in sensor response time when detecting a high molecular weight analyte (streptavidin) versus in the flow-over PSi approach. This work demonstrates the possibility of integrating multiple flow-through PSi sensor membranes within parallel microarrays for rapid and multiplexed label-free biosensing.

Prefabricated surfaces containing α-cyano-4-hydroxycinnamic acid and trypsin have been developed to facilitate enzymatic digestion of endogenous tissue proteins prior to matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). Tissue sections are placed onto slides that were previously coated with α-cyano-4-hydroxycinnamic acid and trypsin. After incubation to promote enzymatic digestion, the tissue is analyzed by MALDI IMS to determine the spatial distribution of the tryptic fragments. The peptides detected in the MALDI IMS dataset were identified by Liquid chromatography-tandem mass spectrometry/mass spectrometry. Protein identification was further confirmed by correlating the localization of unique tryptic fragments originating from common parent proteins. Using this procedure, proteins with molecular weights as large as 300 kDa were identified and their distributions were imaged in sections of rat brain. In particular, large proteins such as myristoylated alanine-rich C-kinase substrate (29.8 kDa) and spectrin alpha chain, non-erythrocytic 1 (284 kDa) were detected that are not observed without trypsin. The pre-coated targets simplify workflow and increase sample throughput by decreasing the sample preparation time. Further, the approach allows imaging at higher spatial resolution compared with robotic spotters that apply one drop at a time. Copyright © 2016 John Wiley & Sons, Ltd.

The favorable conductive properties of carbon nanotubes (CNTs) offer opportunities for constructing CNT-based nanocomposites with improved thermal conduction for a range of potential applications. Such lightweight composite materials are expected to have thermal properties that depend on their CNT volume fraction and operating temperature. The lack of available CNT processing methods that are compatible with multi-laminated composite structures is one of the largest challenges facing the construction of CNT-based nanocomposites.

Efficient mass transport through porous networks is essential for achieving rapid response times in sensing applications utilizing porous materials. In this work, we show that open-ended porous membranes can overcome diffusion challenges experienced by closed-ended porous materials in a microfluidic environment. A theoretical model including both transport and reaction kinetics is employed to study the influence of flow velocity, bulk analyte concentration, analyte diffusivity, and adsorption rate on the performance of open-ended and closed-ended porous sensors integrated with flow cells. The analysis shows that open-ended pores enable analyte flow through the pores and greatly reduce the response time and analyte consumption for detecting large molecules with slow diffusivities compared with closed-ended pores for which analytes largely flow over the pores. Experimental confirmation of the results was carried out with open- and closed-ended porous silicon (PSi) microcavities fabricated in flow-through and flow-over sensor configurations, respectively. The adsorption behavior of small analytes onto the inner surfaces of closed-ended and open-ended PSi membrane microcavities was similar. However, for large analytes, PSi membranes in a flow-through scheme showed significant improvement in response times due to more efficient convective transport of analytes. The experimental results and theoretical analysis provide quantitative estimates of the benefits offered by open-ended porous membranes for different analyte systems.

This work examines the influence of charge density and surface passivation on the DNA-induced corrosion of porous silicon (PSi) waveguides in order to improve PSi biosensor sensitivity, reliability, and reproducibility when exposed to negatively charged DNA molecules. Increasing the concentration of either DNA probes or targets enhances the corrosion process and masks binding events. While passivation of the PSi surface by oxidation and silanization is shown to diminish the corrosion rate and lead to a saturation in the changes by corrosion after about 2 h, complete mitigation can be achieved by replacing the DNA probe molecules with charge-neutral PNA probe molecules. A model to explain the DNA-induced corrosion behavior, consistent with experimental characterization of the PSi through Fourier transform infrared spectroscopy and prism coupling optical measurements, is also introduced.

Porous silicon structures have been demonstrated as effective biosensors due to their large surface area, size-selective filtering capabilities, and tunable optical properties. However, porous silicon surfaces are highly susceptible to oxidation and corrosion in aqueous environments and solutions containing negative charges. In DNA sensing applications, porous silicon corrosion can mask the DNA binding signal as the typical increase in refractive index that results from a hybridization event can be countered by the decrease in refractive index due to corrosion of the porous silicon matrix. Such signal ambiguity should be eliminated in practical devices. In this work, we carefully examined the influence of charge density and surface passivation on the corrosion process in porous silicon waveguides in order to control this process in porous silicon based biosensors. Both increased DNA probe density and increased target DNA concentration enhance the corrosion process, leading to an overall blueshift of the waveguide resonance. While native porous silicon structures degrade upon prolonged exposure to solutions containing negative charges, porous silicon waveguides that are sufficiently passivated to prevent oxidation/corrosion in aqueous solution exhibit a saturation effect in the corrosion process, which increases the reliability of the sensor. For practical implementation of porous silicon DNA sensors, the negative charges from DNA must be mitigated. We show that a redshift of the porous silicon waveguide resonance results from either replacing the DNA target with neutral charge PNA or introducing Mg2+ ions to shield the negative charges of DNA.