Yu-Cheng Hsiao

Surface modification is an important field and widely applied to biosensors, biomaterials, and semiconductors. Mercapto propyl trimethoxyl silane (MPTMS) is a most common material applied to surface modification in biosensor chips. However, MPTMS is moisture sensitive, slow to modify reaction rates with substrate surfaces, and unstable due to thiol groups, which restrict the expansibility of MPTMS. Previously, we synthesized mercapto propyl silatrane (MPS) to improve moisture sensitivity and increase reactivity with substrate surfaces. Despite these improvements, MPS still requires a high-polarity organic solvent environment and the thiol groups remain susceptible to oxidation by oxygen. The utility of mercaptan-functionalized films critically depends on their stability under ambient conditions. As global environmental awareness increases, developing stable and environmentally friendly silane molecules has become increasingly important. In this report, we explored different protective groups (acetyl- (Ac-), di-tert-butyl carboxyl- (Boc-), and triphenylmethyl- (trityl-)) to cap the mercapto group of MPS, enhancing the stability of the thiol group. We characterized the Boc-MPS, Ac-MPS, and trityl-MPS modifications on substrates using contact angle measurements, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Additionally, we tracked the kinetic rate of capping MPS modification on substrates by using gold nanoparticles (AuNPs). Our results indicated that all protective groups successfully inhibited the oxidation of the thiol groups. Notably, some protective groups (Ac- and Boc-) increase the water solubility. By tracking the rate of Ac-MPS modification on glass surfaces using AuNPs, we observed that Ac-MPS demonstrated a higher surface modification effectiveness than MPS. Furthermore, the water solubility of Ac-MPS allowed for modification on both glass and plastic substrates in aqueous solutions, significantly broadening the application scope of Ac-MPS for various substrate modifications. In this study, we also tested the LSPR refractive index sensitivity of mercapto propyl trimethoxysilane (MPTMS) and Ac-MPS anchored AuNPs on a glass substrate. The results revealed that glass substrates with Ac-MPS anchored AuNPs exhibited greater sensitivity compared with MPTMS coatings. Interestingly, the refractive index test indicated that plastic substrates with Ac-MPS anchored AuNPs showed better sensitivity than glass substrates. This work presents a novel approach to enhancing the stability, water solubility, and surface coating efficiency of MPS through structural extension. We believe that this method can be widely applied to silatrane extensions, potentially eliminating the need for organic solvents in sol-gel surface modification systems. This work significantly expands the applications of silatrane in green chemistry and sustainable development.

Wheat is a global staple, but its main protein, "gluten," can trigger severe reactions in people with celiac disease, an autoimmune disorder affecting around 1% of the population. The only treatment is a lifelong gluten-free diet. Gliadin, a gluten component, is the primary trigger and is difficult to detect due to its low solubility. This makes it challenging for celiac patients to safely eat out or to enjoy diverse foods. To address this, we developed LEO (Lateral flow Enhanced by Optical imaging), a portable gluten detection system combining lateral flow assays with smartphone-based image analysis. LEO uses IoT-enhanced technology to deliver results in under 3 min, accurately quantifying gliadin with over 98% accuracy and sensitivity below the FDA's 20 ppm threshold. In real-world trials, LEO successfully detected hidden gluten in mislabeled "gluten-free" restaurant dishes. With its fast, accurate results and user-friendly design, LEO supports safer food choices for individuals with celiac disease and is suitable for personal, clinical, industrial, and regulatory use.

In recent years, food allergies and food sensitivities have remained critical public health problems that affect approximately 15% of the global population. Wheat is a major food source worldwide, but it is also a common food allergen. Celiac disease is chronic immune-mediated enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals; it can be treated only through strict gluten avoidance. Therefore, rapid gluten detection is crucial for protecting the health of patients. Gluten contains two primary water-insoluble proteins: gliadin and glutenin. Gliadin is a key contributor to celiac disease and poses challenges for sample pretreatment owing to its insolubility, thereby reducing the accuracy and sensitivity of detection systems. Rapid sample processing is a critical problem in gliadin detection. In this report, we developed a gliadin sensor system called the integrated food allergy and microorganism sensor (iFAMs). The iFAMs comprises a gliadin lateral flow chip, a one-pot extraction solution, and an image assay app. The iFAMs enables gliadin extraction and detection in under 2 min with high sensitivity (0.04 mg/kg for gliadin, lower than the regulatory limit of 20 mg/kg). Users can easily measure gluten concentrations in samples and quantify gliadin levels using the smartphone-based image assay app. In samples collected from restaurants, the iFAMs successfully detected hidden gluten within "gluten-free" food items. The compact size and user-friendly design of the iFAMs render it suitable for not only consumers but also clinicians, food industries, and regulators to enhance food safety.

Accurate and timely identification of infections is crucial for effective treatment and controlling disease spread. While single biomarkers have traditionally served diagnostic purposes, their sensitivity and specificity limitations call for a more comprehensive approach. Simultaneous detection of multiple biomolecules shows promise in improving accuracy, expediting analysis, and enhancing pathology screening. Therefore, there is a pressing need to develop a noninvasive biosensor capable of quantifying various infection-associated biomarkers concurrently, such as albumin proteins and bacterial molecules. In this endeavor, a novel biosensor has been developed, leveraging a color-indicating optical platform that utilizes gold nanoisland films (AuNIFs) enveloped by cholesteric liquid crystals (CLCs). The integration of CLCs and AuNIFs capitalizes on their sensitive interfacial interactions, highlighting the potential for robust biosensing. Changes in biomolecule concentrations induce discernible alterations in the CLCs–AuNIFs interface alignment, profoundly impacting the hybrid plasmonic–photonic behavior of AuNIFs. The resulting CLCs–AuNIFs biosensor demonstrates exceptional sensitivity and precision in detecting E. coli concentrations and albumin levels. Notably, the biosensor achieves a label-free limit of detection, with an impressive sensitivity of 1 × 106 CFU/ml for E. coli and 10 ng/ml for bovine serum albumin (BSA). This innovative biosensor offers rapid detection, visual clarity, label-free operation, and the ability to detect multiple concentrations of both microbial agents and albumin. Changes in biomolecule concentrations induce noticeable shifts in interface alignment, thereby modulating the hybrid plasmonic–photonic dynamics of AuNIFs. The potential applications of this advancement span biomedical, microbial, and industrial sectors. This unified biosensor has the potential to revolutionize infection-related diagnostics and containment measures, serving as an ideal point-of-care solution. This ground-breaking development leads the way in multi-biomarker detection in infection diagnosis, with profound implications for future of infection diagnostics and therapeutic interventions.

Gluten is a well-known food allergen globally, and it can induce immune responses in celiac- and nonceliac gluten-sensitive patients. The gliadin proteins from gluten have a special amino acid sequence that make it hydrophobic. One way to deal with gluten allergies is to provide a gluten-free diet. The hydrophobic characteristic of gliadin makes gliadin detection more difficult. An analyst needs to use an organic solvent or multiple processes to denature gluten for extraction. Although organic solvents can rapidly extract gluten in a sample, organic solvent also denatures the antibody and induces false biotest results without buffer dilute, and the accuracy will reduce with buffer dilute. An ionic liquid (IL) is a highly modifiable green chemical organic salt. The imidazolium has a cationic structure and is modified with different lengths (C = 0, 1, 3, 5, 7, 9, and 12) of carbon side chains with organic and inorganic anions [methanesulfonate (MSO), Cl^–, F^–, NO₃^–, HSO₄^–, and H₂PO₄^–] to make different kinds of ILs for testing the solubility of gliadin. Different IL/water ratios were used to test the solubility of gluten. We measured the solubility of gliadin in different imidazolium ILs, and the kinetic curve of gliadin dissolved in 1% [C5DMIM][MSO]_aq was conducted. We also used circular dichroism spectroscopy and an enzyme-linked immunosorbent assay to measure the gliadin structure and the effect of binding with an antibody after 1% [C5DMIM][MSO]_aq treatment. An 2,3-bis-(2-methoxy-4- nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay was used to test the toxicity of [C5DMIM][MSO]_aq in N2a cells. In our research, 1% [C5DMIM][MSO]_aq produced a good solubility of gluten, and it could dissolve more than 3000 ppm of gluten in 5 min. [C5DMIM][MSO]_aq did not break down the gluten structure and did not restrict antibody binding to gluten, and more importantly, [C5DMIM][MSO] did not exhibit cell toxicity. In this report, we showed that [C5DMIM][MSO] could be a good extraction solution applied for gluten detection.

Alkaline etching refines surface properties of BiVO₄. Three alkaline etching methods including hydrothermal, soaking, and electrodeposition processes are applied to tailor surface properties of BiVO₄ as photocatalyst for OER.

Gluten is a well-known food allergen globally, capable of triggering immune responses in both celiac and non-celiac gluten-sensitive individuals. Gluten comprises two major proteins: glutenin and gliadin. Gliadin, in particular, possesses a unique hydrophobic amino acid sequence. The Food and Drug Administration asserts that the toxicity of gliadin cannot be eliminated through fermentation and hydrolysis processes. A common approach to addressing gluten allergies is to adopt a gluten-free diet. However, the hydrophobic nature of gluten makes its detection challenging. Analysts often resort to using organic solvents or employing multiple procedures to denature gluten for extraction. It’s worth noting that while organic solvents can rapidly extract gluten from a sample, they may also alter antibodies, leading to erroneous bio-test results. Ionic liquid (IL) is a highly adaptable green chemical compound consisting of organic salts. We modified imidazolium, a cationic structure, with various carbon side chain lengths (C=0, 1, 3, 5, 7, 9, and 12), and combined it with organic and inorganic anions (e.g., OMs-, Cl-, F-, NO¬3-, HSO4-, and H2PO4-). We used different IL-to-water ratios to assess gluten solubility. We measured the solubility of gliadin in various imidazolium ILs and conducted kinetic studies on the dissolution of gliadin in 1% [C5DMIM][OMs]aq. Additionally, circular dichroism (CD) spectroscopy and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate the structural changes in gliadin and its interaction with antibodies after treatment with 1% [C5DMIM][OMs]aq. An XTT assay was conducted to assess the cytotoxicity of [C5DMIM][OMs]aq on N2a cells. Our research findings indicate that 1% [C5DMIM][OMs]aq demonstrated excellent gluten solubility, dissolving more than 3000 ppm of gluten within 5 minutes. Importantly, [C5DMIM][OMs]aq did not disrupt the gluten structure, did not impede antibody binding to gluten, and exhibited no cell toxicity. This report highlights [C5DMIM][OMs] as a promising extraction solution for gluten detection.

We successfully achieved the synergistic development of a paper fiber-based biosensor that is label-free, flexible, portable, and color-indicating using chiral-nematic liquid crystals (LCs), also known as cholesteric LCs (CLCs). This method can be applied for quick screening in applications such as precision medicine. Optically active nematic LCs were layered in CLCs in various configurations and rotated around different axes. When light struck the LCs, the reflected light consisted of light of specific wavelengths. Using polarized optical microscopy and a charged couple device (CCD), we titrated bovine serum albumin (BSA) on the paper substrate and quantified the protein based on the observed color shift. Using internal Python pixel analysis software, we assessed the red, green, and blue color components that acted as biomarkers for different BSA concentrations. Results showed a linear relationship between the BSA concentration and color changes. This biosensor has the potential to quickly screen a large number of samples, increasing the effectiveness of illness identification in clinical settings. The CLC-based paper-substrate biosensor was developed using the color-indicating and measurable properties of CLCs, while also possessing the affordable and portable properties of paper substrate biosensors. With its easy, quick, and sensitive detection capabilities, disease detection may become more effective in the future.

We successfully achieved the synergistic development of a paper fiber-based biosensor that is label-free, flexible, portable, and color-indicating using chiral-nematic liquid crystals (LCs), also known as cholesteric LCs (CLCs). This method can be applied for quick screening in applications such as precision medicine. Optically active nematic LCs were layered in CLCs in various configurations and rotated around different axes. When light struck the LCs, the reflected light consisted of light of specific wavelengths. Using polarized optical microscopy and a charged couple device (CCD), we titrated bovine serum albumin (BSA) on the paper substrate and quantified the protein based on the observed color shift. Using internal Python pixel analysis software, we assessed the red, green, and blue color components that acted as biomarkers for different BSA concentrations. Results showed a linear relationship between the BSA concentration and color changes. This biosensor has the potential to quickly screen a large number of samples, increasing the effectiveness of illness identification in clinical settings. The CLC-based paper-substrate biosensor was developed using the color-indicating and measurable properties of CLCs, while also possessing the affordable and portable properties of paper substrate biosensors. With its easy, quick, and sensitive detection capabilities, disease detection may become more effective in the future.

Timely and precise identification of infections is pivotal for effective treatment and curtailing disease transmission. While single biomarkers have historically served diagnostic purposes, their limitations in sensitivity and specificity necessitate a more comprehensive approach. The simultaneous detection of multiple biomolecules holds promise in enhancing accuracy, expediting analysis, and bolstering pathology screening. Thus, the imperative to engineer a noninvasive biosensor capable of concurrently quantifying diverse infection-associated biomarkers, such as albumin proteins and bacterial molecules, is undeniable. In this pursuit, a novel biosensor has been synergistically developed, harnessing a color-indicating optical platform employing gold nanoisland films (AuNIFs) enveloped by cholesteric liquid crystals (CLCs). The integration of CLCs and AuNIFs capitalizes on their sensitive interfacial interactions, underscoring the potential for robust biosensing. Variations in biomolecule concentrations trigger discernible alterations in CLC-AuNIF interface alignment, thus profoundly impacting the hybrid plasmonic-photonic behavior of AuNIFs. The resulting CLCs-AuNIFs biosensor showcases exceptional sensitivity and precision in discerning E.coli concentrations and albumin levels. Notably, the biosensor boasts a label-free limit of detection, achieving an impressive 1 × 106 CFU/ml for E.coli and 10 ng/ml for BSA. This innovative CLCs-AuNIFs biosensor boasts swiftness, visual discernibility, label-free operation, and multi-concentration detection capabilities for both microbial agents and albumin. Perturbations in biomolecule concentrations elicit definable shifts in interface alignment, subsequently modulating the hybrid plasmonic-photonic dynamics of AuNIFs. The spectrum of potential applications for this advancement spans biomedical, microbial, and industrial domains. The unified biosensor can revolutionize infection-related diagnostics and containment measures, ideally situated as a point-of-care solution. This landmark development pioneers the realm of multi-biomarker detection in infection diagnosis, holding profound implications for the trajectory of infection diagnostics and therapeutic interventions.