Breakup-Free and Colorful Liquid Metal Thin Films via Electrochemical Oxidation.

Thin-film metal conductors featuring high conductivity and stretchability are basic building blocks for high-performance conformable electronics. Gallium-based liquid metals are attractive candidates for thin-film conductors due to their intrinsic stretchability and ease of processing. Moreover, the phase change nature of liquid metal provides an opportunity to create conformal electronics in a substrate-free manner. However, thin liquid metal films tend to break during the solid-to-liquid transition due to the high surface tension of liquid metal. Here, we created breakup-free liquid metal thin films by the electrochemical oxidation of solid gallium films. We show that electrochemical oxidation can enhance the mechanical strength of the gallium oxide layer and its interfacial adhesion to the gallium core. When heated to the liquid state, the oxidized gallium films can maintain their structural integrity on various solid substrates, hydrogels, and even the water surface. The solid-liquid phase change-induced stiffness decrease allowed the gallium films to be conformably attached to various nonplanar surfaces upon heating or water transfer printing. Moreover, we also found that enhanced electrochemical oxidation can result in the formation of structure color due to nanoporous structures on the film surface. We also demonstrate the applications of oxidized liquid metal films in functional electronics, electrophysiological monitoring, and tattoo art.

Fluorescence-coded logarithmic-dilution digital droplet PCR for ultrawide-dynamic-range nucleic acid quantification.

Digital PCR (dPCR) is considered the next generation of nucleic acid detection for its ability of absolute quantification and high sensitivity. However, when compared to the current gold standard, quantitative PCR (qPCR), dPCR is falling behind by several orders of magnitude in dynamic range, which limits its clinical applicability. Here we present fluorescence-coded logarithmic-dilution digital droplet PCR (Flodd-PCR) that features a dynamic range across 7 orders of magnitude, over 2 orders higher than conventional dPCR (4-5 log range) and approaching that of qPCR (7-8 log range). Flodd-PCR realizes such a wide dynamic range by dividing ∼20,000 droplets into 4 groups, each featuring a unique dilution factor of the loaded DNA template and thus a shifted dynamic range. This is achieved by a microfluidic chip that performs multi-step serial dilution (20-925 folds) and droplet generation. The post-PCR droplets can be clustered in silico based on their dilution indicator fluorescence and analyzed independently. Experimentally, Flodd-PCR can detect 4-20,000,000 copies/µL (cp./µL) of the synthetic human papillomavirus (HPV) DNA and outperforms standard dPCR when analyzing clinical HPV samples. Furthermore, Flodd-PCR can be implemented with existing dPCR system set-up with minimal adjustment, and therefore will also have wide practicality in different applications which conventional dPCR has already demonstrated.

DNA tetrahedron-mediated immune-sandwich assay for rapid and sensitive detection of PSA through a microfluidic electrochemical detection system.

Prostate-specific antigen (PSA) is the most widely used biomarker for the early diagnosis of prostate cancer. Existing methods for PSA detection are burdened with some limitations and require improvement. Herein, we developed a novel microfluidic-electrochemical (µFEC) detection system for PSA detection. First, we constructed an electrochemical biosensor based on screen-printed electrodes (SPEs) with modification of gold nanoflowers (Au NFs) and DNA tetrahedron structural probes (TSPs), which showed great detection performance. Second, we fabricated microfluidic chips by DNA TSP-Au NF-modified SPEs and a PDMS layer with designed dense meandering microchannels. Finally, the µFEC detection system was achieved based on microfluidic chips integrated with the liquid automatic conveying unit and electrochemical detection platform. The µFEC system we developed acquired great detection performance for PSA detection in PBS solution. For PSA assays in spiked serum samples of the µFEC system, we obtained a linear dynamic range of 1-100 ng/mL with a limit of detection of 0.2 ng/mL and a total reaction time <25 min. Real serum samples of prostate cancer patients presented a strong correlation between the "gold-standard" chemiluminescence assays and the µFEC system. In terms of operation procedure, cost, and reaction time, our method was superior to the current methods for PSA detection and shows great potential for practical clinical application in the future.

Bio-Separated and Gate-Free 2D MoS2 Biosensor Array for Ultrasensitive Detection of BRCA1.

2D molybdenum disulfide (MoS2)-based thin film transistors are widely used in biosensing, and many efforts have been made to improve the detection limit and linear range. However, in addition to the complexity of device technology and biological modification, the compatibility of the physical device with biological solutions and device reusability have rarely been considered. Herein, we designed and synthesized an array of MoS2 by employing a simple-patterned chemical vapor deposition growth method and meanwhile exploited a one-step biomodification in a sensing pad based on DNA tetrahedron probes to form a bio-separated sensing part. This solves the signal interference, solution erosion, and instability of semiconductor-based biosensors after contacting biological solutions, and also allows physical devices to be reused. Furthermore, the gate-free detection structure that we first proposed for DNA (BRCA1) detection demonstrates ultrasensitive detection over a broad range of 1 fM to 1 µM with a good linear response of R2 = 0.98. Our findings provide a practical solution for high-performance, low-cost, biocompatible, reusable, and bio-separated biosensor platforms.

Electrochemical DNA Sensor for Sensitive BRCA1 Detection Based on DNA Tetrahedral-Structured Probe and Poly-Adenine Mediated Gold Nanoparticles.

BRCA1 is the biomarker for the early diagnosis of breast cancer. Detection of BRCA1 has great significance for the genetic analysis, early diagnosis and clinical treatment of breast cancer. In this work, we developed a simple electrochemical DNA sensor based on a DNA tetrahedral-structured probe (TSP) and poly-adenine (polyA) mediated gold nanoparticles (AuNPs) for the sensitive detection of BRCA1. A thiol-modified TSP was used as the scaffold on the surface of the screen-printed AuNPs electrode. The capture DNA (TSP) and reporter DNA were hybridized to the target DNA (BRCA1), respectively, to form the typical sandwich system. The nanocomposites of reporter DNA (polyA at the 5' end) combined with AuNPs were employed for signal amplification which can capture multiple enzymes by the specificity between biotin and streptavidin. Measurements were completed in the electrochemical workstation by cyclic voltammetry and amperometry and we obtained the low limit of detection of 0.1 fM with the linear range from 1 fM to 1 nM. High sensitivity and good specificity of the proposed electrochemical DNA sensor showed potential applications in clinical early diagnosis for breast cancer.

Poly-adenine-mediated spherical nucleic acids for strand displacement-based DNA/RNA detection.

DNA-gold nanoparticles (AuNPs) conjugate is one of the most versatile bionanomaterials for biomedical and clinical diagnosis. However, to finely tune the hybridization ability and precisely control the orientation and conformation of surface-tethered oligonucleotides on AuNPs remains a hurdle. In this work, we developed a poly adenine-mediated spherical nucleic acid (polyA-mediated SNA) strategy by assembling di-block DNA probes on gold nanoparticles (AuNPs) to spatially control interdistance and hybridization ability of oligonucleotides on AuNPs. By modulating length of poly A bound on the SNA with different degrees of constructing, we presented significant improved biosensing performance including high hybridization efficiency, and expanded dynamic range of analytes with more sensitive detection limit. Furthermore, this polyA design could facilitate the programmable detection for DNA in serum environment and simultaneous multicolor detection of three different microRNAs associated with pancreatic carcinoma. The demonstration of the link between modulation of SNA assembly strategy and biodetection capability will increase the development of high performance diagnostic tools for translational biomedicine.