Conformal Hydrogel-Skin Coating on a Microfluidic Channel through Microstamping Transfer of the Masking Layer.

Poly(dimethylsiloxane) (PDMS) is used in microfluidics owing to its biocompatibility and simple fabrication. However, its intrinsic hydrophobicity and biofouling inhibit its microfluidic applications. Conformal hydrogel-skin coating for PDMS microchannels, involving the microstamping transfer of the masking layer, is reported herein. A selective uniform hydrogel layer with a thickness of ∼1 µm was coated in diverse PDMS microchannels with a resolution of ∼3 µm, maintaining its structure and hydrophilicity after 180 days (6 months). The wettability transition of PDMS was demonstrated through the switched emulsification in a flow-focusing device (water-in-oil [pristine PDMS] to oil-in-water [hydrophilic PDMS]). A one-step bead-based immunoassay was performed to detect the anti-severe acute respiratory syndrome coronavirus 2 IgG using a hydrogel-skin-coated point-of-care platform.

High-throughput fabrication of high aspect ratio Ag/Al nanopillars for optical detection of biomarkers.

Nanomaterial-based optical techniques for biomarker detection have garnered tremendous attention from the nanofabrication community due to their high precision and enhanced limit of detection (LoD) features. These nanomaterials are highly responsive to local refractive index (RI) fluctuations, and their RI unit sensitivity can be tuned by varying the chemical composition, geometry, and dimensions of the utilized nanostructures. To improve the sensitivity and LoD values of these nanomaterials, it is common to increase both dimensions and aspect ratios of the fabricated nanostructures. However, limited by the complexity, prolonged duration, and elevated costs of the available nanofabrication techniques, mass production of these nanostructures remains challenging. To address not only high accuracy, but also speed and production effectiveness in these nanostructures' fabrication, our work reports, for the first time, a fast, high-throughput, and cost-effective nanofabrication protocol for routine manufacturing of polymer-based nanostructures with high sensitivity and calculated LoD in the pM range by utilizing anodized aluminum oxide (AAO) membranes as templates. Specifically, our developed platform consists of arrays of nearly uniform polystyrene nanopillars with an average diameter of ∼185 nm and aspect ratio of ∼11. We demonstrate that these nanostructures can be produced at a high speed and a notably low price, and that they can be efficiently applied for biosensing purposes after being coated with aluminum-doped silver (Ag/Al) thin films. Our platform successfully detected very low concentrations of human C-reactive protein (hCRP) and SARS-CoV-2 spike protein biomarkers in human plasma samples with LoDs of 11 and 5 pM, respectively. These results open new opportunities for day-to-day fabrication of high aspect ratio arrays of nanopillars that can be used as a base for nanoplasmonic sensors with competitive LoD values. This, in turn, contributes to the development of point-of-care devices and further improvement of the existing nanofabrication techniques, thereby enriching the fields of pharmacology, clinical analysis, and diagnostics.

Reversed-engineered human alveolar lung-on-a-chip model.

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.

Surface Biochemical Modification of Poly(dimethylsiloxane) for Specific Immune Cytokine Response.

Recent evidence suggests that proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), play a pivotal role in the development of inflammatory-related pathologies (covid-19, depressive disorders, sepsis, cancer, etc.,). More importantly, the development of TNF-α biosensors applied to biological fluids (e.g. sweat) could offer non-invasive solutions for the continuous monitoring of these disorders, in particular, polydimethylsiloxane (PDMS)-based biosensors. We have therefore investigated the biofunctionalization of PDMS surfaces using a silanization reaction with 3-aminopropyltriethoxysilane, for the development of a human TNF-α biosensor. The silanization conditions for 50 µm PDMS surfaces were extensively studied by using water contact angle measurements, electron dispersive X-ray and Fourier transform infrared spectroscopies, and fluorescamine detection. Evaluation of the wettability of the silanized surfaces and the Si/C ratio pointed out to the optimal silanization conditions supporting the formation of a stable and reproducible aminosilane layer, necessary for further bioconjugation. An ELISA-type immunoassay was then successfully performed for the detection and quantification of human TNF-α through fluorescent microscopy, reaching a limit of detection of 0.55 µg/mL (31.6 nM). Finally, this study reports for the first time a promising method for the development of PDMS-based biosensors for the detection of TNF-α, using a quick, stable, and simple biofunctionalization process.