Controllable-Swelling Microneedle-Assisted Ultrasensitive Paper Sensing Platforms for Personal Health Monitoring.

Microneedle (MN) patches, which allow the extraction of skin interstitial fluid (ISF) without a pain sensation, are powerful tools for minimally invasive biofluid sampling. Herein, an MN-assisted paper-based sensing platform that enables rapid and painless biofluid analysis with ultrasensitive molecular recognition capacity is developed. First, a controllable-swelling MN patch is constructed through the engineering of a poly(ethylene glycol) diacrylate/methacrylated hyaluronic acid hydrogel; it combines rapid, sufficient extraction of ISF with excellent structural integrity. Notably, the analyte molecules in the needles can be recovered into a moist cellulose paper through spontaneous diffusion. More importantly, the paper can be functionalized with enzymatic colorimetric reagents or a plasmonic array, enabling a desired detection capacity-for example, the use of paper-based surface-enhanced Raman spectroscopy sensors leads to label-free, trace detection (sub-ppb level) of a diverse set of molecules (cefazolin, nicotine, paraquat, methylene blue). Finally, nicotine is selected as a model drug to evaluate the painless monitoring of three human volunteers. The changes in the nicotine levels can be tracked, with the levels varying significantly in response to the metabolism of drug in different volunteers. This as-designed minimally invasive sensing system should open up new opportunities for precision medicine, especially for personal healthcare monitoring.

Direct Thermal Growth of Gold Nanopearls on 3D Interweaved Hydrophobic Fibers as Ultrasensitive Portable SERS Substrates for Clinical Applications.

Surface-enhanced Raman spectroscopy (SERS)-based biosensors have attracted much attention for their label-free detection, ultrahigh sensitivity, and unique molecular fingerprinting. In this study, a wafer-scale, ultrasensitive, highly uniform, paper-based, portable SERS detection platform featuring abundant and dense gold nanopearls with narrow gap distances, are prepared and deposited directly onto ultralow-surface-energy fluorosilane-modified cellulose fibers through simple thermal evaporation by delicately manipulating the atom diffusion behavior. The as-designed paper-based SERS substrate exhibits an extremely high Raman enhancement factor (3.9 × 1011 ), detectability at sub-femtomolar concentrations (single-molecule level) and great signal reproductivity (relative standard deviation: 3.97%), even when operated with a portable 785-nm Raman spectrometer. This system is used for fingerprinting identification of 12 diverse analytes, including clinical medicines (cefazolin, chloramphenicol, levetiracetam, nicotine), pesticides (thiram, paraquat, carbaryl, chlorpyrifos), environmental carcinogens (benzo[a]pyrene, benzo[g,h,i]perylene), and illegal drugs (methamphetamine, mephedrone). The lowest detection concentrations reach the sub-ppb level, highlighted by a low of 16.2 ppq for nicotine. This system appears suitable for clinical applications in, for example, i) therapeutic drug monitoring for individualized medication adjustment and ii) ultra-early diagnosis for pesticide intoxication. Accordingly, such scalable, portable and ultrasensitive fibrous SERS substrates open up new opportunities for practical on-site detection in biofluid analysis, point-of-care diagnostics and precision medicine.

Substrate-independent adsorption of nanoparticles as anti-biofilm coatings.

Healthcare-associated infections are common causes of morbidity and mortality. Advanced nanotechnology provides a means of overcoming this problem, but it remains challenging to develop universal coating strategies for decorating antimicrobial nanomaterials onto various clinical devices. In this paper, we propose a general silane-based method for immobilizing monolayer metal nanoparticle (NP) arrays onto any type of substrate surface-especially for a diverse range of clinical implantable devices. The surface silanization was achieved simply through the adsorption of N1-(3-trimethoxysilylpropyl)diethylenetriamine (TMS), regardless of the material (polymer, metal, oxide) or morphology (flat, curved, textured) of the substrate, with no need for pretreatment or expensive instrumentation. Monolayers of various nanostructures (Ag, Au, and hollow Au NPs) were then decorated rapidly onto the TMS-treated substrates, thereby further functionalizing their surfaces. In particular, immobilization of the Ag NPs resulted in excellent anti-biofilm efficacy against three clinically life-threatening pathogens: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. Sustained release of Ag+ ions led to durable inhibition of bacterial attachment for up to 28 days. Studies with NIH3T3 fibroblasts revealed that the Ag NP arrays displayed no cytotoxicity toward mammalian cells. Overall, this universal coating process appears to be an innovative method for the surface-functionalization of diverse materials and devices employed in the fields of energy, sensing, and medicine-especially to prevent healthcare-associated infections arising from the use of clinical implantable devices in hospitals.

Near-IR-Absorbing Gold Nanoframes with Enhanced Physiological Stability and Improved Biocompatibility for In Vivo Biomedical Applications.

This paper describes the synthesis of near-infrared (NIR)-absorbing gold nanoframes (GNFs) and a systematic study comparing their physiological stability and biocompatibility with those of hollow Au-Ag nanoshells (GNSs), which have been used widely as photothermal agents in biomedical applications because of their localized surface plasmon resonance (LSPR) in the NIR region. The GNFs were synthesized in three steps: galvanic replacement, Au deposition, and Ag dealloying, using silver nanospheres (SNP) as the starting material. The morphology and optical properties of the GNFs were dependent on the thickness of the Au coating layer and the degree of Ag dealloying. The optimal GNF exhibited a robust spherical skeleton composed of a few thick rims, but preserved the distinctive LSPR absorbance in the NIR region-even when the Ag content within the skeleton was only 10 wt %, 4-fold lower than that of the GNSs. These GNFs displayed an attractive photothermal conversion ability and great photothermal stability, and could efficiently kill 4T1 cancer cells through light-induced heating. Moreover, the GNFs preserved their morphology and optical properties after incubation in biological media (e.g., saline, serum), whereas the GNSs were unstable under the same conditions because of rapid dissolution of the considerable silver content with the shell. Furthermore, the GNFs had good biocompatibility with normal cells (e.g., NIH-3T3 and hepatocytes; cell viability for both cells: >90%), whereas the GNSs exhibited significant dose-dependent cytotoxicity (e.g., cell viability for hepatocytes at 1.14 nM: ca. 11%), accompanied by the induction of reactive oxygen species. Finally, the GNFs displayed good biocompatibility and biosafety in an in vivo mouse model; in contrast, the accumulation of GNSs caused liver injury and inflammation. Our results suggest that GNFs have great potential to serve as stable, biocompatible NIR-light absorbers for in vivo applications, including cancer detection and combination therapy.

3-D imaging and illustration of mouse intestinal neurovascular complex.

Because of the dispersed nature of nerves and blood vessels, standard histology cannot provide a global and associated observation of the enteric nervous system (ENS) and vascular network. We prepared transparent mouse intestine and combined vessel painting and three-dimensional (3-D) neurohistology for joint visualization of the ENS and vasculature. Cardiac perfusion of the fluorescent wheat germ agglutinin (vessel painting) was used to label the ileal blood vessels. The pan-neuronal marker PGP9.5, sympathetic neuronal marker tyrosine hydroxylase (TH), serotonin, and glial markers S100B and GFAP were used as the immunostaining targets of neural tissues. The fluorescently labeled specimens were immersed in the optical clearing solution to improve photon penetration for 3-D confocal microscopy. Notably, we simultaneously revealed the ileal microstructure, vasculature, and innervation with micrometer-level resolution. Four examples are given: 1) the morphology of the TH-labeled sympathetic nerves: sparse in epithelium, perivascular at the submucosa, and intraganglionic at myenteric plexus; 2) distinct patterns of the extrinsic perivascular and intrinsic pericryptic innervation at the submucosal-mucosal interface; 3) different associations of serotonin cells with the mucosal neurovascular elements in the villi and crypts; and 4) the periganglionic capillary network at the myenteric plexus and its contact with glial fibers. Our 3-D imaging approach provides a useful tool to simultaneously reveal the nerves and blood vessels in a space continuum for panoramic illustration and analysis of the neurovascular complex to better understand the intestinal physiology and diseases.