Lateral flow immunoassay (LFA) is an attractive detection tool due to its low cost, compact size, and ease of use. However, the inconsistent porosities and pore sizes in commercial lateral flow nitrocellulose (NC) membrane materials often lead to false signals caused by unwashed conjugate particles trapped within the structure and impurities absorbed due to high surface activity. Cellulose acetate (CA) membranes have potential for LFA applications as an environmental-friendly alternative, but their preparation process still needs to be optimized specifically for LFA. In this study, we present, for the first time, an electrospun CA fibrous membrane for LFA, replacing commercial NC or CA membrane, for the detection of C-reactive protein (CRP). The CA membrane was designed and prepared by electrospinning, subsequently integrated into a lateral flow device, and the effects of precursor powder, electrospinning distance, and electrospun solution usage on the microstructure and LFA signals were systematically investigated. The electrospun CA membrane exhibited a sixfold faster flow time than a commercial CA membrane for CRP detection, while maintaining comparable sensitivity and reducing false signals relative to commercial membranes. Clinical tests further validated the potential of our electrospun CA membrane by achieving accurate and reliable CRP detection. This work provides fundamental knowledge for developing lateral flow devices and highlights the potential for a wide range of applications in detecting protein biomarkers for clinical diseases.

Wearable biosensors leverage microfluidic technology for precise biofluid sampling and directional transport, and utilize electrical or optical sensing mechanisms for reliable detection of target physiological parameters. By synergizing microfluidics and sensing technologies, these devices provide innovative solutions for biomarker monitoring, demonstrating broad potential in health tracking and chronic disease management. With ongoing advances in smart materials, multiplex detection capabilities, and artificial intelligence-driven technologies, wearable biosensors are evolving into cornerstone tools for telemedicine and precision diagnostics. This work reviews recent progress in microfluidic-integrated wearable biosensors for disease diagnostics and health monitoring. We systematically examine sensing approaches for different analytes based on their biological characteristics, covering three key categories: (1) metabolite sensing, including microneedle-based detection, noninvasive optical/electrical methods, multimodal platforms, and closed-loop diabetes management systems; (2) protein sensing, encompassing both label-free and labeled electrical/optical techniques; and (3) nucleic acid sensing, which involves sampling protocols, amplification strategies, and label-free detection approaches. The review highlights the interaction between biomarker biological characteristics, sensing strategies, and microfluidic approaches in the development of wearable biosensing platforms, and is expected to guide the development of next-generation intelligent disease diagnostics and health monitoring devices.

Lateral flow immunoassays (LFAs) are widely used because of their simplicity, rapid readout, and low cost; however, quantitative performance is often limited by insufficient signal intensity and background interference from the membrane substrate. This issue becomes more severe when high-brightness fluorescent nanolabels are introduced: conventional nitrocellulose (NC) membranes tend to exhibit autofluorescence and strong light scattering and can also promote nonspecific retention of nanoparticles, which elevates background and compromises quantitative reliability. Here, we present a "fluorescent nanodiamond-electrospun fibrous membrane" strategy, in which a fibrous electrospun cellulose acetate (ECA) membrane replaces the NC membrane and photostable nitrogen-vacancy center nanodiamonds (NVDs) serve as fluorescent labels. The uniform fibrous architecture of the ECA membrane reduces scattering and substrate-derived fluorescence; meanwhile, the fibrous network facilitates smoother convective wash-through, mitigating nonspecific adsorption and mechanical trapping of nanoparticles. As a result, unbound labels are more efficiently removed, leading to suppressed background signals and improved quantitative robustness. Using this platform, we achieved sensitive detection of cardiac troponin I (cTnI) with a limit of detection of ∼0.009 ng/mL, markedly better than conventional NC-based LFA strips. Clinical testing further confirms the diagnostic performance and consistency of the proposed approach. This work offers a simple route to enhance LFA sensitivity and quantification and is readily extendable to other point-of-care biosensing applications.

Effective anti-aging interventions require bioactive molecules to penetrate skin barrier and reach underlying tissues to exert functions, however, the highly ordered stratum corneum poses a formidable challenge for transdermal delivery. This study develops linalool-modified liposomes to load potential anti-aging drug, TPEN, (Lin-TPEN-Lips) for enhancing skin permeation and retention of drug, thus improving anti-aging efficacy. Strikingly, the incorporation of linalool induces the formation of a kind of bilocular vesicle structure, which increases the membrane fluidity and modulates the lipid organization of stratum corneum, leading to an obviously enhanced transdermal delivery efficiency compared to unmodified liposomes. Both in vitro and in vivo experiments show that Lin-TPEN-Lips effectively reduces oxidative stress and inflammation, suppresses matrix metalloproteinase (MMP) expression, promotes collagen production, and alleviates skin senescence. The present work proves that linalool-modified liposomes represent a promising strategy to ameliorate the transdermal delivery performance of bioactive molecules for enhanced skin anti-aging application.

Upconversion nanoparticles (UCNPs)-based fluorescence lateral flow immunoassay (FLFIA) has significant application prospects in clinical diagnosis, but it still suffers from relatively low sensitivity in detecting trace amounts of biomarkers. Here, we report for the first time a strong fluorescence-emitting core-shell-shell NaLuF4@NaLuF4:Yb,Er@NaLuF4 UCNP as the FLFIA probe. The UCNPs-based FLFIA platform enables point-of-care detection of cardiac troponin I (cTnI) with high sensitivity, accuracy, and resistance to autofluorescence interference. NaLuF4:Yb,Er encapsulated in the intermediate shell layer can effectively reduce the cross-relaxation and surface quenching of the luminescence center, resulting in a higher quantum yield. Compared with the conventional core-shell NaLuF4:Yb,Er@NaLuF4 UCNPs, the fluorescence intensity increases by 2.4 times. The UCNPs-based FLFIA was further integrated with a portable smartphone platform for rapid, on-site detection. The UCNPs probe enabled sensitive cTnI detection, with a detection limit of 0.035 ng/mL in buffer and 0.059 ng/mL in serum, and a detection range of 0.05-100 ng/mL. In testing clinical samples, the results from the platform showed excellent correlation with hospital results. We anticipate that the NaLuF4@NaLuF4:Yb,Er@NaLuF4 UCNPs can serve as a promising immunolabeling nanoprobe for highly sensitive and accurate FLFIA detection.

The detection of ferritin is essential for diagnosing conditions such as excessive blood transfusions, malnutrition, liver disease, various malignancies, iron deficiency anemia, nutritional anemia, and blood loss. However, conventional diagnostic methods face challenges, including time consumption, complex procedures, bulky equipment, and interference from background signal. In this study, we introduce, for the first time, a strong fluorescent NaLuF4:Yb,Er, Mg upconversion nanoparticle (UCNPs)-based lateral flow immunoassay (LFIA) platform for ferritin detection. The Mg doped UCNPs provide enhanced luminescence intensity, which is 17 times and 2 times greater than that of conventional NaLuF4:Yb, Er and NaLuF4:Yb,Er@NaLuF4 UCNPs, respectively. Meanwhile, the core-only structure requires less preparation time as LFIA probes. Using sandwich LFIA technology, the fluorescence intensity of NaLuF4:Yb,Er, Mg UCNPs correlates with the ferritin concentration as the detection signal, which can be conveniently readout using a smartphone platform. This LFIA platform with optimized UCNP probes offers several advantages, including high sensitivity, wide detection range and high stability. The ferritin detection demonstrated low detection limits of 0.050 ng/mL in buffer and 0.109 ng/mL in whole blood, as well as a wide detection range from 0.1 to 200 ng/mL. This work presents an effective UCNP probe for the point-of-care detection of ferritin and offers insights into the probe design of high-performance LFIA.

The Lateral flow immunoassay (LFIA) has been widely used in environmental monitoring and disease diagnosis due to its advantages of low cost, simple operation, and convenience. However, its accuracy and sensitivity remain major challenges to be addressed. D-dimer is an important biomarker for thrombotic diseases. In this work, we show for the first time a core–shell Au@Ag nanoparticle (NP) labeled colorimetrically enhanced LFIA for D-dimer detection. The superior performance of Au@Ag LFIA stems from the silver shell's enhancement of plasmon resonance, which boosts optical signals to yield brighter scattering and superior visual contrast. Compared with conventional AuNPs, Au@AgNPs significantly improve sensitivity, leading to more accurate results. The detection limit for D-dimer was improved by approximately tenfold, reaching 1 ng/mL, due to the improved cross-coupling efficiency of Au@AgNPs compared with AuNPs. We anticipate that, with further development and validation, this enhanced LFIA could become a valuable tool in a wide range of clinical diagnostic applications.

Lateral flow assay (LFA), as one of the most well-known methods in point-of-care testing platforms, has attracted great interest in disease detection due to its low cost, portability, ease of use, and short response time. However, the sensitivity of LFA and its widespread application in disease monitoring remain challenging problems. Herein, we report a liquid-phase barrier-modified nitrocellulose (NC) membrane in chemiluminescence LFA (CL-LFA) for the detection of cardiac troponin I (cTnI), which shows high sensitivity, specificity, and stability. The dissolvable paraffin liquid barrier increases the viscosity of the applied analyte solution and also the reaction time on the test and control lines during flow, significantly improving the performance of the device. The modified CL-LFA device achieved highly sensitive detection in the concentration range of about 0.1-20 ng·mL-1. Clinical samples from acute myocardial infarction patients were also tested with the modified NC-based LFA, which showed good agreement with hospital results. Our method breaks new ground in improving the detection performance of LFA and thus has great potential for monitoring protein biomarker levels in various scenarios.

BACKGROUND:Lateral flow immunoassays (LFA) are widely used for disease diagnostics due to their simplicity and portability. However, they often suffer from limited sensitivity and accuracy, making them unsuitable for quantitative detection. Additionally, the adsorption and non-specific interactions between label particles and the nitrocellulose membrane may lead to increased background noise, which compromises the repeatability of the device. Therefore, there is an urgent need to develop a highly sensitive, accurate, and high signal-to-noise ratio LFA device that is free from background noise interference. RESULTS:We developed a miniaturized LFA platform that achieves dual-enhanced colorimetric and chemiluminescence signals with ultra-low background noise for detecting cardiac troponin I. The enhancement is achieved through the sequential addition of horseradish peroxidase-streptavidin (HRP-SA) and multiple layers of biotin-antibody (Bio-Ab) conjugated to gold nanoparticles. This conjugation alters the surface charge state of the particles, reducing nonspecific adsorption to the nitrocellulose membrane and significantly lowering background noise. Additionally, the multilayered Bio-Ab coatings and the robust interaction between streptavidin and biotin markedly increase antibody loading, further enhancing the device's sensitivity. A compact smartphone-based imaging setup combined with a high-resolution lens was used for signal readout. The assay strip demonstrated a colorimetric detection range of 100 pg/mL to 10 ng/mL and a chemiluminescent detection range of 10 pg/mL to 10 ng/mL. SIGNIFICANCE:This work establishes a new foundational methodology for chemiluminescence LFA, offering a simpler and more accessible approach that does not require complex equipment, making it ideal for the rapid and on-site diagnosis of acute myocardial infarction. We firmly believe that this method holds great potential for widespread applications in sensitive, and rapid disease diagnosis.

Lateral flow immunoassays typically rely on optical tests conducted on paper strips. However, the 3D matrix of paper embedded with optical nanoparticles often limits detection sensitivity and the ability of detection instruments to capture signals. This study introduces a novel approach using a glass chip-based lateral flow immunoassay, with albumin as a typical biomarker for detection, enabling the presence of the signal on a flat surface. Compared with traditional paper-based immunoassay, glass-based lateral flow immunoassay has achieved a uniform distribution pattern for albumin detection, lowered the limit of detection from 100 ng/mL to 1 ng/mL, and reduced detection time through an improved liquid mobility system. The glass-based method also shortens the detection time by 28.5

Piroxicam is a common painkiller and antiinflammatory drug. Precise monitoring of piroxicam levels can mitigate side effects, but current methods are often slow and complicated. An easily fabricated and highly sensitive voltammetric sensor for piroxicam was developed by drop-coating a composite of multi-walled carbon nano-tubes (MWCNTs) and Nafion onto the electrode surface. The morphological and electrochemical characteristics of the Nafion-MWCNTs composite film were analyzed to reveal the synergistic effects of Nafion and MWCNTs. The composite film was then applied to modify a glassy carbon electrode (GCE), which served as a voltammetric sensor for the detection of piroxicam. When compared to previous reports, the sensor demonstrated efficient electrochemical oxidation of piroxicam with remarkable sensitivity, reproducibility, and stability. Under optimized conditions, the Nafion/MWCNTs/GCE exhibited a linear voltammetric response for piroxicam in the concentration range of 5 x 10-9 to 8 x 10-6 mol L-1 and 8 x 10-6 to 6 x 10-5 mol L-1 respectively, with a detection limit of 4 x 10-9 mol L-1. The sensor was successfully applied to detect piroxicam in real tablet samples, providing satisfactory recovery values. Furthermore, the composite film was applied to the surface of a platinum microelectrode, resulting in a micro-sensor for piroxicam detection. With the typical small size and the radial diffusion field, the micro-sensor of piroxicam exhibited increased sensitivity and possessed unique properties. Particularly, fast and accurate response across various piroxicam concentrations was achieved without the necessity of additional forced-convection for preconcentration, demonstrating its great potential for in vivo determination of piroxicam.

Lateral flow assays (LFA) have become increasingly important for point-of-care disease detection for low costs, portability, and rapid results. To improve chemiluminescence LFA (CL-LFA) performance, we present a way to make test (T) and control (C) line areas transparent by applying paraffin liquid to the nitrocellulose (NC) membrane without inducing structure deterioration. The transparent T and C line regions generate stronger light signals in CL-LFA compared with conventional LFA, where the NC membrane obstructs signals from inner conjugates. A tunable transparency ranging from 12.47

Colorimetric lateral flow assays (LFAs) are widely used for detecting analytes through color changes displayed by conjugates on a test strip, typically made of materials such as nitrocellulose (NC) membranes. However, a significant number of conjugate nanoparticles become trapped within the membrane's porous structure, preventing the full display of color information. Here, gelation of a porous NC membrane is achieved by introducing dimethyl sulfoxide (DMSO) into an LFA strip, resulting in structural changes and high transparency in the NC membrane, exposing red-colored Au nanoparticles within a transparent and portable DMSO/NC membrane. Under optimized conditions (16 mu L of 50 vol % DMSO in water and heating the NC strip at 80 degrees C for 8 min), the membrane becomes highly transparent, achieving 77.42% transmittance while maintaining its capability to effectively perform LFAs for cardiac troponin I (cTnI) in both buffer solutions and clinical samples. We anticipate that this method holds promise for advancing fundamental studies of lateral flow strip materials and has potential applications in healthcare and environmental monitoring.

Integrated artificial pancreas devices with continuous glucose monitoring (CGM) and closed-loop insulin delivery are crucial for diabetes management. However, design challenges remain, including miniaturization, low cost, stability, and low power consumption. Current commercial products are expensive ($3,000 to $8,000 USD), and bulky, typically exceeding 100 cm3. Here, a closed-loop bioelectronic artificial pancreas patch is presented for continuous blood glucose regulation in diabetic rats and pigs. By designing transiently dissolvable microneedle arrays incorporated with microtube arrays, insulin is efficiently delivered into interstitial fluid, eliminating the need for an external long needle. Leveraging multi-layer sensing electrodes, Ag/Ag2O glass-fiber pumping electrodes, and a polyethylene-glycol (PEG) functionalized polycarbonate membrane, the closed-loop artificial pancreas patch demonstrates highly stable sensing and pumping with low power consumption (only 0.422 mW), enabling long-term continuous operation to regulate blood glucose. In particular, diabetic pigs are operated on for 3 consecutive days, showing steady blood glucose control with a time in range (3.9-10.0 mm) of ≈67.98%, comparable to a commercial closed-loop system at ≈74.95%. The total volume of the entire system is ≈2 cm3, and the cost is ≈$10. This method opens up promising avenues for the development and application of wearable devices to manage diabetes.

Cardiac troponin I (cTnI) is a highly specific biomarker of cardiomyocyte injury, released during cell disintegration and necrosis, and is the gold standard for diagnosing acute myocardial infarction (AMI). At the onset of AMI, cTnI appears in very low concentrations (pg/mL level), necessitating the development of highly sensitive and rapid detection sensors. In this study, an electrochemiluminescence lateral flow immunosensor (ECL-LFI) was designed using luminol-labeled silver nanoparticles (luminol@AgNPs) for the sensitive and quantitative detection of cTnI. A screen-printed electrode (SPE) was integrated beneath the nitrocellulose (NC) membrane with plastic plates of the same thickness applied on both sides of the SPE to ensure a smooth flow surface. Upon addition of cTnI and the luminol-H2O2 system, sandwich immune complexes formed by antibody-functionalized luminol@AgNPs on the strips generated electrochemiluminescent (ECL) signals. The ECL-LFI exhibited a broad linear detection range from 5 pg/mL to 100 ng/mL, with a detection limit as low as 1.6 pg/mL. Additionally, the results show excellent correlation with clinical tests, demonstrating that the ECL-LFI provides a promising point-of-care tool for the early diagnosis of AMI and other diseases.

The development of novel diabetes monitoring sensors is important for the diabetes management of millions of diabetic patients. This work reports a flexible filamentary continuous glucose monitoring (CGM) sensor. A multilayer CGM sensor has been constructed on titanium filament with low cost and ease of use. The sensor, made of flexible material, offers better adaptability and comfort than traditional rigid filament CGM sensors, allowing continuous monitoring of subcutaneous blood glucose levels to provide patients with treatment strategies. The performance and reliability of the sensor were verified through rat experiments. The trend of the increase and decrease of the detected current was generally consistent with the actual blood glucose, and the detected values were located in regions A and B of the Clarke error grid. The results show that the sensor has the advantages of high sensitivity, high accuracy and fast response speed, which is suitable for monitoring the blood glucose level for a long time and has a broad application prospect in diabetes monitoring, exercise monitoring, health management and clinical application.

The development of a wearable, easy-to-fabricate, and stable intelligent minisystem is highly desired for the closed-loop management of diabetes. Conventional systems always suffer from large size, high cost, low stability, or complex fabrication. Here, we show for the first time a wearable, rapidly manufacturable, stability-enhancing microneedle patch for diabetes management. The patch consists of a graphene composite ink-printed sensor on hollow microneedles, a polyethylene glycol (PEG)-functionalized electroosmotic micropump integrated with the microneedles, and a printed circuit board for precise and intelligent control of the sensor and pump to detect interstitial glucose and deliver insulin through the hollow channels. Via synthesizing and printing the graphene composite ink, the sensor fabrication process is fast and the sensing electrodes are stable. The PEG functionalization enables the micropump a significantly higher stability in delivering insulin, extending its lifetime from days to weeks. The patch successfully demonstrated excellent blood glucose control in diabetic rats. This work may introduce a new paradigm for building new closed-loop systems and shows great promise for widespread use in patients with diabetes.

In order to improve the living standards of diabetes patients and reduce the negative health effects of this disease, the medical community has been actively searching for more effective treatments. In recent years, an artificial pancreas has emerged as an important approach to managing diabetes. Despite these recent advances, meeting the requirements for miniaturized size, accurate sensing and large-volume pumping capability remains a great challenge. Here, we present a novel miniaturized artificial pancreas based on a long microtube sensor integrated with an ultrasonic pump. Our device meets the requirements of achieving both accurate sensing and high pumping capacity. The artificial pancreas is constructed based on a long microtube that is low cost, painless and simple to operate, where the exterior of the microtube is fabricated as a glucose sensor for detecting diabetes and the interior of the microtube is used as a channel for delivering insulin through an ultrasonic pump. This work successfully achieved closed-loop control of blood glucose and treatment of diabetes in rats. It is expected that this work can open up new methodologies for the development of microsystems, and advance the management approach for diabetes patients.

The development of sensors for the detection of albumin concentrations in urine is essential for the long-term detection and treatment of kidney disease. Albumin is an important biomarker for kidney diseases. However, albumin concentrations in patient's urine are often too high (more than 0.15 mg/mL), causing competitive lateral flow immunoassays (LFIAs) to exceed detection ranges. In this work, we report for the first time a one-step, fluorescent lateral-flow quantification of human urine albumin using an in situ minipump and clinical evaluation in renal patients, eliminating the need for external sample dilution. The device is constructed by integrating a LFIA strip and an in situ minipump that sits above the sample/conjugate pad of the strip. The detection is based on competitive immunoassay by using fluorescent nanoparticles as the probe, and the in situ pump performs on-chip dilution. The linear detection range with this device is 0.1-10 mg/mL for a 1000-fold dilution of the sample with the pump, and 1-100 mg/mL for a 10 000-fold dilution. The device can be used for the direct quantification of albumin in the urine of patients with clinical kidney disease. We anticipate that the work can open up exciting new opportunities for the quantification of protein biomarkers, and their wide range of applications in clinical and home-settings.