Mechanism and application of ß-adrenoceptor blockers in soft tissue wound healing.

Soft tissue damage stimulates sympathetic nerves to release large amounts of catecholamine hormones which bind to ß-adrenergic receptors (ß-ARs) on the cell membrane surface. It activates the downstream effector molecules and impairs soft tissue wound healing. ß-blockers specifically inhibit ß-ARs activation in acute/chronic skin lesions and ulcerative hemangiomas. They also accelerate soft tissue wound healing by shortening the duration of inflammation, speeding keratinocyte migration and reepithelialization, promoting wound contraction and angiogenesis, and inhibiting bacterial virulence effects. In addition, ß-blockers shorten wound healing periods in patients with severe thermal damage by reducing the hypermetabolic response. While ß-blockers promote/inhibit corneal epithelial cell regeneration and restores limbal stem/progenitor cells function, it could well accelerate/delay corneal wound healing. Given these meaningful effects, a growing number of studies are focused on examining the efficacy and safety of ß-blockers in soft tissue wound repair, including acute and chronic wounds, severe thermal damage, ulcerated infantile hemangioma, corneal wounds, and other soft tissue disorders. However, an intensive investigation on their acting mechanisms is imperatively needed. The purpose of this article is to summerize the roles of ß-blockers in soft tissue wound healing and explore their clinical applications.

Autonomous robotic system for the assisted immediate placement of a maxillary anterior implant: A clinical report.

Precise reproduction of the preoperatively designed 3-dimensional (3D) implant position is key to seating a prefabricated restoration and restoring esthetics. Static and dynamic computer-aided implant surgery (CAIS) based on the fusion of 3D imaging files have been used to improve implant accuracy. However, both techniques have shortcomings that can be remedied by a robotic system. This clinical report describes the immediate placement of an implant in the anterior esthetic zone by using an autonomous dental implant robotic system (ADIR).

Accuracy of an autonomous dental implant robotic system versus static guide-assisted implant surgery: A retrospective clinical study.

STATEMENT OF PROBLEM: The accuracy of implant placement is a prerequisite for prosthetically driven implant surgery and is necessary to ensure the long-term stability of dental implants. Imprecise implant position may bring difficulties for restoration, damage anatomic structures, affect peri-implant tissues, and lead to ultimate implant failure. PURPOSE: The purpose of this retrospective clinical study was to compare the accuracy of implants placed with an autonomous dental implant robotic (ADIR) system with those placed with static computer assisted implant surgery (sCAIS). MATERIAL AND METHODS: Thirty-nine participants were enrolled in this retrospective study: 20 participants had received implant surgery with the ADIR system and 19 participants had implants placed with sCAIS. The preoperative plans and postoperative cone beam computed tomography (CBCT) scans after implant placement were matched during the study. The coronal, apical, and angular deviations were measured and analyzed. A linear regression model was established to analyze the source of deviation. MANOVA was used to compare differences in the major outcome variables (α=.05). RESULTS: A total of 60 implants were placed in 39 participants (30 in each of the 2 groups). The mean ±standard deviation coronal, apical, and angular deviation of the ADIR system group and sCAIS group were 0.43 ±0.18 mm versus 1.31 ±0.62 mm (P<.001), 0.56 ±0.18 mm versus 1.47 ±0.65 mm (P<.001), and 1.48 ±0.59 degrees versus 2.42 ±1.55 degrees (P=.003), respectively. In addition, there was no significant difference in accuracy in the different implant regions (anterior, premolar, molar, maxilla, mandible) (P>.05). No complications were observed. CONCLUSIONS: The accuracy of the implant position using the ADIR system was significantly higher than with sCAIS, suggesting that the ADIR system can achieve minimally invasive and excellent accuracy. In addition, implant regions had no significant influence on the accuracy of implant placement. (Keywords: Robotic system, Implant surgery, Static guide, Autonomous, Accuracy).

Visual Quantitative Detection of Circulating Tumor Cells with Single-Cell Sensitivity Using a Portable Microfluidic Device.

Immunocytological technologies, molecular technologies, and functional assays are widely used for detecting circulating tumor cells (CTCs) after enrichment from patients' blood sample. Unfortunately, accessibility to these technologies is limited due to the need for sophisticated instrumentation and skilled operators. Portable microfluidic devices have become attractive tools for expanding the access and efficiency of detection beyond hospitals to sites near the patient. Herein, a volumetric bar chart chip (V-Chip) is developed as a portable platform for CTC detection. The target CTCs are labeled with aptamer-conjugated nanoparticles (ACNPs) and analyzed by V-Chip through quantifying the byproduct (oxygen) of the catalytic reaction between ACNPs and hydrogen peroxide, which results in the movement of an ink bar to a concentration-dependent distance for visual quantitative readout. Thus, the CTC number is decoded into visually quantifiable information and a linear correlation can be found between the distance moved by the ink and number of cells in the sample. This method is sensitive enough that a single cell can be detected. Furthermore, the clinical capabilities of this system are demonstrated for quantitative CTC detection in the presence of a high leukocyte background. This portable detection method shows great potential for quantification of rare cells with single-cell sensitivity for various applications.

Microfluidic Distance Readout Sweet Hydrogel Integrated Paper-Based Analytical Device (µDiSH-PAD) for Visual Quantitative Point-of-Care Testing.

A disposable, equipment-free, versatile point-of-care testing platform, microfluidic distance readout sweet hydrogel integrated paper-based analytical device (µDiSH-PAD), was developed for portable quantitative detection of different types of targets. The platform relies on a target-responsive aptamer cross-linked hydrogel for target recognition, cascade enzymatic reactions for signal amplification, and microfluidic paper-based analytic devices (µPADs) for visual distance-based quantitative readout. A "sweet" hydrogel with trapped glucoamylase (GA) was synthesized using an aptamer as a cross-linker. When target is present in the sample, the "sweet" hydrogel collapses and releases enzyme GA into the sample, generating glucose by amylolysis. A hydrophilic channel on the µPADs is modified with glucose oxidase (GOx) and colorless 3,3'-diaminobenzidine (DAB) as the substrate. When glucose travels along the channel by capillary action, it is converted to H2O2 by GOx. In addition, DAB is converted into brown insoluble poly-3,3'-diaminobenzidine [poly(DAB)] by horseradish peroxidase, producing a visible brown bar, whose length is positively correlated to the concentration of targets. The distance-based visual quantitative platform can detect cocaine in urine with high selectivity, sensitivity, and accuracy. Because the target-induced cascade reaction is triggered by aptamer/target recognition, this method is widely suitable for different kinds of targets. With the advantages of low cost, ease of operation, general applicability, and disposability with quantitative readout, the µDiSH-PAD holds great potential for portable detection of trace targets in environmental monitoring, security inspection, personalized healthcare, and clinical diagnostics.

Target-responsive DNA hydrogel mediated "stop-flow" microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets.

A versatile point-of-care assay platform was developed for simultaneous detection of multiple targets based on a microfluidic paper-based analytic device (µPAD) using a target-responsive hydrogel to mediate fluidic flow and signal readout. An aptamer-cross-linked hydrogel was used as a target-responsive flow regulator in the µPAD. In the absence of a target, the hydrogel is formed in the flow channel, stopping the flow in the µPAD and preventing the colored indicator from traveling to the final observation spot, thus yielding a "signal off" readout. In contrast, in the presence of a target, no hydrogel is formed because of the preferential interaction of target and aptamer. This allows free fluidic flow in the µPAD, carrying the indicator to the observation spot and producing a "signal on" readout. The device is inexpensive to fabricate, easy to use, and disposable after detection. Testing results can be obtained within 6 min by the naked eye via a simple loading operation without the need for any auxiliary equipment. Multiple targets, including cocaine, adenosine, and Pb(2+), can be detected simultaneously, even in complex biological matrices such as urine. The reported method offers simple, low cost, rapid, user-friendly, point-of-care testing, which will be useful in many applications.

Simple and Rapid Functionalization of Gold Nanorods with Oligonucleotides Using an mPEG-SH/Tween 20-Assisted Approach.

DNA conjugated gold nanorods (AuNRs) are widely applied for nanostructure assembly, gene therapy, biosensing, and drug delivery. However, it is still a great challenge to attach thiolated DNA on AuNRs, because the positively charged AuNRs readily aggregate in the presence of negatively charged DNA. This article reports an mPEG-SH/Tween 20-assisted method to load thiolated DNA on AuNRs in 1 h. Tween 20 and mPEG-SH are used to synergistically displace CTAB on the surface of AuNRs by repeated centrifugation and resuspension, and thiolated DNA are attached to AuNRs in the presence of 1 M NaCl, 100 mM MgCl2, or 100 mM citrate. AuNRs with different sizes and aspect ratios can be functionalized with DNA by this method. The number of DNA loaded on each AuNR can be easily controlled by the concentrations of mPEG-SH and Tween 20 or the ratio between DNA and AuNR. Functionalized AuNRs were used for nanoparticle assembly and cancer cell imaging to confirm that DNA anchored on the surface of AuNRs retains its hybridization and molecular recognition capability. The new method is easy, rapid, and robust for the preparation of DNA functionalized AuNRs for a variety of applications such as cancer therapy, drug delivery, self-assembly, and imaging.

Translating Molecular Recognition into a Pressure Signal to enable Rapid, Sensitive, and Portable Biomedical Analysis.

Herein, we demonstrate that a very familiar, yet underutilized, physical parameter­gas pressure­can serve as signal readout for highly sensitive bioanalysis. Integration of a catalyzed gas-generation reaction with a molecular recognition component leads to significant pressure changes, which can be measured with high sensitivity using a low-cost and portable pressure meter. This new signaling strategy opens up a new way for simple, portable, yet highly sensitive biomedical analysis in a variety of settings.

Facile and rapid generation of large-scale microcollagen gel array for long-term single-cell 3D culture and cell proliferation heterogeneity analysis.

Microfabricated devices are suitable for single-cell analysis due to their high throughput, compatible dimensions and controllable microenvironment. However, existing devices for single-cell culture and analysis encounter some limitations, such as nutrient depletion, random cell migration and complicated fluid shear influence. Moreover, most of the single-cell culture and analysis devices are based on 2D cell culture conditions, even though 3D cell culture methods have been demonstrated to better mimic the real cell microenvironment in vivo. To solve these problems, herein we develop a microcollagen gel array (µCGA) based approach for high-throughput long-term single-cell culture and single-cell analysis under 3D culture conditions. Type-I collagen, a well-established 3D cell culture medium, was used as the scaffold for 3D cell growth. A 2 × 2 cm PDMS chip with 10 000 µCGA units was fabricated to encapsulate thousands of single cells in less than 15 min. Single cells were able to be confined and survive in µCGA units for more than 1 month. The capability of large-scale and long-term single-cell 3D culture under open culture conditions allows us to study cellular proliferation heterogeneity and drug cytotoxicity at the single-cell level. Compared with existing devices for single-cell analysis, µCGA solves the problems of nutrient depletion and random cellular migration, avoids the influence of complicated fluid shear, and mimics the real 3D growth environment in vivo, thereby providing a feasible 3D long-term single-cell culture method for single-cell analysis and drug screening.

Au@Pt nanoparticle encapsulated target-responsive hydrogel with volumetric bar-chart chip readout for quantitative point-of-care testing.

Point-of-care testing (POCT) with the advantages of speed, simplicity, portability, and low cost is critical for the measurement of analytes in a variety of environments where access to laboratory infrastructure is lacking. While qualitative POCTs are widely available, quantitative POCTs present significant challenges. Here we describe a novel method that integrates an Au core/Pt shell nanoparticle (Au@PtNP) encapsulated target-responsive hydrogel with a volumetric bar-chart chip (V-Chip) for quantitative POCT. Upon target introduction, the hydrogel immediately dissolves and releases Au@PtNPs, which can efficiently catalyze the decomposition of H2 O2 to generate a large volume of O2 to move of an ink bar in the V-Chip. The concentration of the target introduced can be visually quantified by reading the traveling distance of the ink bar. This method has the potential to be used for portable and quantitative detection of a wide range of targets without any external instrument.

Association between tumor necrosis factor receptor 2 and progression and poor prognosis of tumor stage 2­3 esophageal squamous cell carcinoma and stratified analysis.

Although tumor necrosis factor receptor 2 (TNFR2) may serve a protumor role in several types of tumors, the clinical significance of TNFR2, including the diagnostic and prognostic value in tumor (T) stage 2-3 esophageal squamous cell carcinoma (ESCC), remains unclear. Therefore, the present study aimed to explore the clinical significance of TNFR2 in stage T2-3 ESCC. The present study collected the mRNA expression data of TNFR2 from two databases and confirmed the high expression of TNFR2 in ESCC tissue. TNFR2 expression in stage T2-3 ESCC tissue (n=404) was detected using immunohistochemistry and a stratified analysis was performed. For all patients with stage T2-3 ESCC, TNFR2 expression was associated with clinical stage, invasion depth and metastatic lymph nodes. Stage T3 and low differentiation was associated with an increase in the risk of lymph node metastasis, but older age was associated with a decrease. TNFR2 expression was associated with poor overall survival (OS) of all patients with stage T2-3 ESCC and stratified patients with stage T3 ESCC. Moreover, TNFR2 expression and metastatic lymph nodes were independent prognostic factors for these patients. For stratified patients aged ≤60 years, TNFR2 expression was associated with clinical stage and metastatic lymph nodes. In addition, TNFR2 expression was associated with poor OS in stratified patients with stage T2 ESCC. The presence of metastatic lymph nodes was also an independent prognostic factor for these patients. For stratified patients aged >60 years, TNFR2 expression was associated with invasion depth. TNFR2 expression was also associated with poor OS in all patients with stage T2-3 ESCC and stratified patients with stage T3 ESCC. TNFR2 expression and metastatic lymph nodes were identified as independent prognostic factors for these patients. In conclusion, TNFR2 expression is associated with progression and poor prognosis in patients with stage T2-3 ESCC as an independent prognostic factor, except in the subgroup of patients with stage T2-3 ESCC aged ≤60 years.

Target-responsive "sweet" hydrogel with glucometer readout for portable and quantitative detection of non-glucose targets.

Portable devices with the advantages of rapid, on-site, user-friendly, and cost-effective assessment are widely applied in daily life. However, only a limited number of quantitative portable devices are commercially available, among which the personal glucose meter (PGM) is the most successful example and has been the most widely used. However, PGMs can detect only blood glucose as the unique target. Here we describe a novel design that combines a glucoamylase-trapped aptamer-cross-linked hydrogel with a PGM for portable and quantitative detection of non-glucose targets. Upon target introduction, the hydrogel collapses to release glucoamylase, which catalyzes the hydrolysis of amylose to produce a large amount of glucose for quantitative readout by the PGM. With the advantages of low cost, rapidity, portability, and ease of use, the method reported here has the potential to be used by the public for portable and quantitative detection of a wide range of non-glucose targets.

HMNet: Hierarchical Multi-Scale Brain Tumor Segmentation Network.

An accurate and efficient automatic brain tumor segmentation algorithm is important for clinical practice. In recent years, there has been much interest in automatic segmentation algorithms that use convolutional neural networks. In this paper, we propose a novel hierarchical multi-scale segmentation network (HMNet), which contains a high-resolution branch and parallel multi-resolution branches. The high-resolution branch can keep track of the brain tumor's spatial details, and the multi-resolution feature exchange and fusion allow the network's receptive fields to adapt to brain tumors of different shapes and sizes. In particular, to overcome the large computational overhead caused by expensive 3D convolution, we propose a lightweight conditional channel weighting block to reduce GPU memory and improve the efficiency of HMNet. We also propose a lightweight multi-resolution feature fusion (LMRF) module to further reduce model complexity and reduce the redundancy of the feature maps. We run tests on the BraTS 2020 dataset to determine how well the proposed network would work. The dice similarity coefficients of HMNet for ET, WT, and TC are 0.781, 0.901, and 0.823, respectively. Many comparative experiments on the BraTS 2020 dataset and other two datasets show that our proposed HMNet has achieved satisfactory performance compared with the SOTA approaches.

Serum Uric Acid Levels in Neurodegenerative Disorders: A Cross-Sectional Study.

BACKGROUND: Excessive oxidative stress may contribute to neurodegeneration by leading to protein aggregation and mitochondrial dysfunction. Uric acid (UA) is an important endogenous antioxidant that protects against oxidative stress, yet its exact role in neurodegeneration remains unclear. OBJECTIVE: To explore the performance of serum UA in neurodegenerative disorders. METHODS: A total of 839 controls and 840 patients, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), motor neuron disease (MND), Creutzfeldt-Jakob disease (CJD), and mixed dementia (MixD) were enrolled. Fasting serum UA levels were measured in all participants and compared between patients and controls. Linear regression models were utilized to explore possible relationships of serum UA with cognition, disease duration, age, and age of onset. RESULTS: Compared to controls (355.48 ±â€Š85.38 µmol/L), serum UA was significantly lower in AD (291.29 ±â€Š83.49 µmol/L, p < 0.001), PD (286.95 ±â€Š81.78 µmol/L, p < 0.001), PSP (313.32 ±â€Š88.19 µmol/L, p < 0.001), FTD (313.89 ±â€Š71.18 µmol/L, p = 0.001), and DLB (279.23 ±â€Š65.51 µmol/L, p < 0.001), adjusting for confounding factors including age, gender, education, etc. In addition, serum UA was positively correlated with cognitive levels in all patients (Mini-Mental State Examination: r = 0.136, p = 0.001; and Montreal Cognitive Assessment Scale: r = 0.108, p = 0.009). CONCLUSION: Decreased levels of serum UA were correlated with AD, PD, PSP, FTD, and DLB, offering significant potential as a promisingly relevant, less-invasive marker of multiple neurodegenerative disorders.

The incidence of gastrointestinal adverse events in patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1 inhibitors: a meta-analysis.

BACKGROUND: We conducted a meta-analysis to evaluates the incidence of the gastrointestinal (GI) adverse events with the use of PD-1 inhibitors among patients with advanced non-small cell lung cancer (NSCLC). METHODS: The PICOs (participants, intervention, comparison, and outcomes) elements were used for the selection of studies to meet the inclusion and exclusion criteria. Google Scholar, PubMed, Science Direct and proceedings of major oncology conferences were systematically searched from their inception to December 2020, to identify studies which reported the GI adverse events of PD-1 inhibitors among patients with NSCLC. Risks of bias were assessed by using a revised methodological index for nonrandomized studies (MINORS). Pooled incidences and weighted relative risk (RR) estimate for GI adverse events, the incidence of treatment discontinuation due to GI adverse events was also calculated. To perform the analysis of qualified studies, the model of random effects was used and the inconsistency of studies with the I2 index was investigated. OpenMeta 10.10, Stata 11.0 and RevMan 5.3 software were used for data analysis. RESULTS: The research included 15 studies comprising of a total of 3,716 patients. The incidences of all-grade GI symptoms were: diarrhea 8.6% (95% CI: 6.6-10.6%), nausea 9.2% (95% CI: 7.3-11.0%), vomiting 3.2% (95% CI: 1.9-4.5%), constipation 2.8% (95% CI: 1.8-3.9%), colitis 0.7% (95% CI: 0.4-1.1%), stomatitis (95% CI: 1.0-2.7%), and decreased appetite 10.0% (95% CI: 8.3-11.7%). Therapy using PD-1 inhibitors was discontinued in 2.5% (95% CI: 0.0-5.1%) of patients with nausea, in 3.0% (95% CI: 0.7-5.3%) of those with diarrhea, and in 45.7% (95% CI: 20.6-70.7%) of patients with colitis. Compared with chemotherapy, the use of PD-1 inhibitors showed significant increase in the occurrence of grade 1-4 colitis (RR =3.90, 95% CI: 1.41-10.81, P=0.009) and grade 3-4 colitis (RR =3.76, 95% CI: 1.07-13.26, P=0.04). DISCUSSION: This meta-analysis provides a reliable estimate of the incidences of GI adverse events among NSCLC patients. Especially when colitis does occur, it often results in therapy discontinuation. Use of PD-1 inhibitors led to a higher incidence of colitis as compared to the use of chemotherapy.

Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis.

This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30-90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13-3.37, P = 0.016) for PFS and 2.70 (95% CI: 1.81-4.02, P < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5-1.7) and 8.8 months (95% CI: 8.5-9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.

An insertion/deletion polymorphism in the 3' untranslated region of beta-transducin repeat-containing protein (betaTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese.

Hepatocellular carcinoma (HCC) is an epithelial cancer which originates from hepatocytes or their progenitors. As a positive regulator of NFkappaB signaling pathway, beta-transducin repeat-containing protein (betaTrCP) is overexpressed and oncogenic in epithelial cancers, suggesting a potential role of betaTrCP in HCC susceptibility. We carried out a case-control study in a Chinese population (256 cases and 367 controls) to estimate the susceptibility to HCC associated with a 9bp insertion/deletion polymorphism (rs16405) in 3' untranslated region of betaTrCP. Using unconditional logistic regression, we found that 9N del/del and 9N ins/del genotypes were significantly associated with decreased HCC risk: OR=0.44 (0.24-0.83) (p=0.004) and OR=0.56 (0.31-1.00) (p=0.034), respectively. Furthermore, in vivo experiments showed that mRNA levels of betaTrCP from HCC tumor tissues were correlated with rs16405 genotypes. HCC tumor tissues with homozygous for 9N ins/ins has the highest level of betaTrCP, which are 3.99 and 7.04-fold higher than heterozygous 9N ins/del and homozygous 9N del/del, respectively. Based on bioinformatics prediction, we found that the risk allele for rs16405 disrupted a binding site for human microRNA-920 which would negatively regulate betaTrCP. We propose a microRNA-920 mediated betaTrCP regulation model depending on rs16405 genotype, which warrants further replication association studies and follow-up functional experiments.

Enhancement of curcumin antitumor efficacy and further photothermal ablation of tumor growth by single-walled carbon nanotubes delivery system in vivo.

Curcumin, a commonly used natural product for antitumor therapy, is unable to achieve full potential due to poor bioavailability. Based on our previous report of a novel delivery system for curcumin using functionalized single-walled carbon nanotubes by phosphatidylcholine and polyvinylpyrrolidone (SWCNT-Cur), we further evaluated SWCNT-Cur's performance in vivo and characteristics in vitro. SWCNT-Cur significantly increased the blood concentration of curcumin, up to 18-fold, in mice. And in a murine S180 tumor model, SWCNT-Cur exhibited significantly higher inhibition efficacy on tumor growth and no obvious toxicity in main organs. Moreover, photothermal therapy induced by SWCNT under near-infrared radiation further facilitated SWCNT-Cur to inhibit the tumor growth in vivo. In addition, solvent residue is negligible in SWCNT-Cur formulation, and hydrogen bonding was formed between void carriers and curcumin, as demonstrated by GC chromatograph and IR spectra. Furthermore, experiments of confocal microscopy and spectrofluorometer showed that SWCNT-Cur gave a six-fold higher uptake for curcumin compared to native curcumin in human prostate cancer PC-3 cells. In conclusion, curcumin delivery with functionalized SWCNT is a promising strategy to enhance anticancer activity in vivo by enhancing cell uptake and blood concentration, changing physicochemical properties of curcumin and combining phototherapeutic with chemotherapeutic effects.

Facile fabrication of microfluidic surface-enhanced Raman scattering devices via lift-up lithography.

We describe a facile and low-cost approach for a flexibly integrated surface-enhanced Raman scattering (SERS) substrate in microfluidic chips. Briefly, a SERS substrate was fabricated by the electrostatic assembling of gold nanoparticles, and shaped into designed patterns by subsequent lift-up soft lithography. The SERS micro-pattern could be further integrated within microfluidic channels conveniently. The resulting microfluidic SERS chip allowed ultrasensitive in situ SERS monitoring from the transparent glass window. With its advantages in simplicity, functionality and cost-effectiveness, this method could be readily expanded into optical microfluidic fabrication for biochemical applications.

Integrating Target-Responsive Hydrogel with Pressuremeter Readout Enables Simple, Sensitive, User-Friendly, Quantitative Point-of-Care Testing.

Point-of-care testing (POCT) with the advantages of speed, simplicity, and low cost, as well as no need for instrumentation, is critical for the measurement of analytes in a variety of environments lacking access to laboratory infrastructure. In the present study, a hydrogel pressure-based assay for quantitative POCT was developed by integrating a target-responsive hydrogel with pressuremeter readout. The target-responsive hydrogels were constructed with DNA grafted linear polyacrylamide and the cross-linking DNA for selective target recognition. The hydrogel response to the target substance allows release of the preloaded Pt nanoparticles, which have good stability and excellent catalytic ability for decomposing H2O2 to O2. Then, the generated O2 in a sealed environment leads to significant pressure increase, which can be easily read out by a handheld pressuremeter. Using this target-responsive hydrogel pressure-based assay, portable and highly sensitive detection of cocaine, ochratoxin A, and lead ion were achieved with excellent accuracy and selectivity. With the advantages of portability, high sensitivity, and simple sample processing, the hydrogel pressure-based assay shows great potential for quantitative POCT of a broad range of targets in resource-limited settings.