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1. Porous silicon on paper sensors: factors affecting biosensing performance

   https://doi.org/10.1117/12.3048667  

   An, Huijin; Laibinis, Paul E; Locke, Andrea K; Weiss, Sharon M (March 2025, SPIE)

   Miller, Benjamin L; Weiss, Sharon M; Danielli, Amos (Ed.)

   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. 

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2. Baseline Stability of Thermally Hydrosilated Porous Silicon with Zwitterionic Antifouling Polymer Coating for Biosensing Applications

   https://doi.org/10.1021/acsomega.5c03495  

   Smail, Soren M; Laibinis, Paul E; Weiss, Sharon M (July 2025, ACS Omega)

   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. 

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3. Designed 2D protein crystals as dynamic molecular gatekeepers for a solid-state device

   https://doi.org/10.1038/s41467-024-50567-8  

   Vijayakumar, Sanahan; Alberstein, Robert G; Zhang, Zhiyin; Lu, Yi-Sheng; Chan, Adriano; Wahl, Charlotte E; Ha, James S; Hunka, Deborah E; Boss, Gerry R; Sailor, Michael J; et al (December 2024, Nature Communications)

   Abstract The sensitivity and responsiveness of living cells to environmental changes are enabled by dynamic protein structures, inspiring efforts to construct artificial supramolecular protein assemblies. However, despite their sophisticated structures, designed protein assemblies have yet to be incorporated into macroscale devices for real-life applications. We report a 2D crystalline protein assembly of^C98/E57/E66L-rhamnulose-1-phosphate aldolase (^CEERhuA) that selectively blocks or passes molecular species when exposed to a chemical trigger.^CEERhuA crystals are engineered via cobalt(II) coordination bonds to undergo a coherent conformational change from a closed state (pore dimensions <1 nm) to an ajar state (pore dimensions ~4 nm) when exposed to an HCN(g) trigger. When layered onto a mesoporous silicon (pSi) photonic crystal optical sensor configured to detect HCN_(g), the 2D^CEERhuA crystal layer effectively blocks interferents that would otherwise result in a false positive signal. The 2D^CEERhuA crystal layer opens in selective response to low-ppm levels of HCN_(g), allowing analyte penetration into the pSi sensor layer for detection. These findings illustrate that designed protein assemblies can function as dynamic components of solid-state devices in non-aqueous environments. 

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4. Novel Fabrication Approach of a Porous Silicon Biocompatible Membrane Evaluated within a Alveolar Coculture Model

   https://doi.org/10.31224/osf.io/mztyc  

   Williams, Marcus_A C; Wiens, Cooper; Hamilton, Adam; Mancha, Sophie; Stalder, Madeline; Vargas, Koby; Crawford, Jerry; Li, Yiyan; Schreiner, Sarah; Blake, David J; et al (October 2021, Engrxiv Engineering Archive)

   The use of conventional in vitro and preclinical animal models often fail to properly recapitulate the complex nature of human diseases and hamper the success of translational therapies in humans [1-3] Consequently, research has moved towards organ-on-chip technology to better mimic human tissue interfaces and organ functionality. Herein, we describe a novel approach for the fabrication of a biocompatible membrane made of porous silicon (PSi) for use in organ-on-chip technology that provides key advantages when modeling complex tissue interfaces seen in vivo. By combining well-established methods in the semiconductor industry with organ-on-chip technology, we have developed a novel way of producing thin (25 μm) freestanding PSi biocompatible membranes with both nano (~15.5 nm diameter pores) and macroporous (~0.5 μm diameter pores) structures. To validate the proposed novel membrane, we chose to recapitulate the dynamic environment of the alveolar blood gas exchange interface in alveolar co-culture. Viability assays and immunofluorescence imaging indicate that human pulmonary cells remain viable on the PSi membrane during long-term culture (14 days). Interestingly, it was observed that macrophages can significantly remodel and degrade the PSi membrane substrate in culture. This degradation will allow for more intimate physiological cellular contact between cells, mimicking a true blood-gas exchange interface as observed in vivo. Broadly, we believe that this novel PSi membrane may be used in more complex organ-on-chip and lab-on-chip model systems to accurately recapitulate human anatomy and physiology to provide further insight into human disease pathology and pre-clinical response to therapeutics. 

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5. Rapid and specific detection of intact viral particles using functionalized microslit silicon membranes as a fouling-based sensor

   https://doi.org/10.1039/D1AN01504D  

   Klaczko, Michael E.; Lucas, Kilean; Salminen, Alec T.; McCloskey, Molly C.; Ozgurun, Baturay; Ward, Brian M.; Flax, Jonathan; McGrath, James L. (January 2022, The Analyst)

   The COVID-19 pandemic demonstrated the public health benefits of reliable and accessible point-of-care (POC) diagnostic tests for viral infections. Despite the rapid development of gold-standard reverse transcription polymerase chain reaction (RT-PCR) assays for SARS-CoV-2 only weeks into the pandemic, global demand created logistical challenges that delayed access to testing for months and helped fuel the spread of COVID-19. Additionally, the extreme sensitivity of RT-PCR had a costly downside as the tests could not differentiate between patients with active infection and those who were no longer infectious but still shedding viral genomes. To address these issues for the future, we propose a novel membrane-based sensor that only detects intact virions. The sensor combines affinity and size based detection on a membrane-based sensor and does not require external power to operate or read. Specifically, the presence of intact virions, but not viral debris, fouls the membrane and triggers a macroscopically visible hydraulic switch after injection of a 40 μL sample with a pipette. The device, which we call the μSiM-DX (microfluidic device featuring a silicon membrane for diagnostics), features a biotin-coated microslit membrane with pores ∼2–3× larger than the intact virus. Streptavidin-conjugated antibody recognizing viral surface proteins are incubated with the sample for ∼1 hour prior to injection into the device, and positive/negative results are obtained within ten seconds of sample injection. Proof-of-principle tests have been performed using preparations of vaccinia virus. After optimizing slit pore sizes and porous membrane area, the fouling-based sensor exhibits 100% specificity and 97% sensitivity for vaccinia virus ( n = 62). Moreover, the dynamic range of the sensor extends at least from 10 5.9 virions per mL to 10 10.4 virions per mL covering the range of mean viral loads in symptomatic COVID-19 patients (10 5.6 –10 7 RNA copies per mL). Forthcoming work will test the ability of our sensor to perform similarly in biological fluids and with SARS-CoV-2, to fully test the potential of a membrane fouling-based sensor to serve as a PCR-free alternative for POC containment efforts in the spread of infectious disease. 

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