Gold nanoparticle–based lateral flow immunoassays (AuNP LFIAs) are widely used point-of-care (POC) sensors for in vitro diagnostics. However, the sensitivity limitation of conventional AuNP LFIAs impedes the detection of trace biomarkers. Several studies have explored the size and shape factors of AuNPs and derivative nanohybrids, showing limited improvements or enhanced sensitivity at the cost of convenience and affordability. Here, we investigated surface chemistry on the sensitivity of AuNP LFIAs. By modifying surface ligands, a surface chemistry strategy involving weakly ionized AuNPs enables ultrasensitive naked-eye LFIAs (~100-fold enhanced sensitivity). We demonstrated how this surface chemistry–amplified immunoassay approach modulates nanointerfacial bindings to promote antibody adsorption and higher activity of adsorbed antibodies. This surface chemistry design eliminates complex nanosynthesis, auxiliary devices, or additional reagents while efficiently improving sensitivity with advantages: simplified fabrication process, excellent reproducibility and reliability, and ultrasensitivity toward various biomarkers. The surface chemistry using weakly ionized AuNPs represents a versatile approach for sensitizing POC sensors.

C-peptide is a critical biomarker for evaluating pancreatic β cell function and managing diabetes. However, conventional methods such as enzyme-linked immunosorbent assay are limited by lengthy processing times and the necessity for invasive sample collection. This study introduces a regenerable, portable, and wearable device for minimally invasive, real-time monitoring of C-peptide in dermal interstitial fluid (ISF). The device uses a microneedle array and negative pressure extraction for ISF collection. A double-antibody sandwich approach was used to detect C-peptide, and an antibody regeneration strategy was applied to remove bound antigen-antibody complexes, thereby achieving repeatable detection, enabling at least 10 detection assays on the same chip with negligible signal attenuation. The compact design features a skin contact area of only 3 cm by 5.4 cm and excellent biocompatibility. Integrated with a mobile app, the device provides real-time concentration reading. Mouse and rabbit tests confirm effective ISF sampling and monitoring accuracy, demonstrating its potential for at-home diabetes management and broader wearable biosensing applications.

Biological particle separation has wide applications in medical diagnosis, bioengineering, and various other domains. Traditional methods, such as filtration, density gradient centrifugation, and size exclusion chromatography, face many challenges, including low separation resolution, low purity, and the inability to be seamlessly integrated into continuous processes. The development of microfluidics has paved the way for efficient and precise biological particle separation. Microfluidic chip‐based methods can generally be performed continuously and automatically, and microfluidic chips can integrate multilevel operations, including mixing, separation, detection, and so forth, thereby achieving continuous processing of particles at various levels. This review comprehensively investigates biological particle separation techniques based on microfluidic chips. According to the different sources of force effect on the particles during the separation process, they can be divided into active separation, passive separation, and affinity separation. We introduce the principles and device design of these methods respectively, and compare their advantages and disadvantages. For the introduction of each method, we used the most classic and latest research cases as much as possible. Additionally, we discussed the differences between experimental standard particles and biological particles. Finally, we summarized the current limitations and challenges of existing microfluidic separation techniques, while exploring future trends and prospects.