Exosomal microRNAs (miRNAs) are reliable and noninvasive biomarkers for the early diagnosis of cancer. Yet, accurate and feasible detection of exosomal miRNAs is often hampered by the low abundance of miRNAs in exosomes and the requirement for RNA extraction in large sample volumes. Here we show a thermophoretic sensor implemented with nanoflares for in situ detection of exosomal miRNAs, without resorting to either RNA extraction or target amplification. Thermophoretic accumulation of nanoflare-treated exosomes leads to an amplified fluorescence signal upon the binding of exosomal miRNAs to nanoflares, allowing for direct and quantitative measurement of exosomal miRNAs down to 0.36 fM in 0.5 μL serum samples. One of the best markers, exosomal miR-375, showed an accuracy of 85% for detection of estrogen receptor-positive breast cancer at early stages (stages I, II). This work provides a feasible tool to improve the diagnosis of cancer.

Molecular profiling of tumor-derived extracellular vesicles (tEVs) holds great promise for non-invasive cancer diagnosis. However, sensitive and accurate identification of tEVs is challenged by the heterogeneity of EV phenotypes which reflect different cell origins. Here we present a DNA computation device mediated by thermophoresis for detection of tEVs. The strategy leverages the aptamer-based logic gate using multiple protein biomarkers on single EVs as the input and thermophoretic accumulation to amplify the output signals for highly sensitive and specific profiling of tEVs. Employing this platform, we demonstrate a high accuracy of 97% for discrimination of breast cancer (BC) patients and healthy donors in a clinical cohort (n = 30). Furthermore, molecular phenotyping assessed by tEVs is in concordance with the results from tissue biopsy in BC patients. The thermophoresis-mediated molecular computation on EVs thus provides new opportunities for accurate detection and classification of cancers.

Molecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC). However, the analysis of EV protein markers has been confounded by the presence of soluble protein counterparts in peripheral blood. Here we use a rapid, sensitive, and low-cost thermophoretic aptasensor (TAS) to profile cancer-associated protein profiles of plasma EVs without the interference of soluble proteins. We show that the EV signature (a weighted sum of eight EV protein markers) has a high accuracy (91.1 %) for discrimination of MBC, non-metastatic breast cancer (NMBC), and healthy donors (HD). For MBC patients undergoing therapies, the EV signature can accurately monitor the treatment response across the training, validation, and prospective cohorts, and serve as an independent prognostic factor for progression free survival in MBC patients. Together, this work highlights the potential clinical utility of EVs in management of MBC.

Rapid and sensitive identification of viral pathogens such as SARS-CoV-2 is a critical step to control the pandemic disease. Viral antigen detection can compete with gold-standard PCR-based nucleic acid diagnostics in terms of better reflection of viral infectivity and reduced risk of contamination from enzymatic amplification. Here, we report the development of a one-step thermophoretic assay using an aptamer and polyethylene glycol (PEG) for direct quantitative detection of viral particles. The assay relies on aptamer binding to the spike protein of SARS-CoV-2 and simultaneous accumulation of aptamer-bound viral particles in laser-induced gradients of temperature and PEG concentration. Using a pseudotyped lentivirus model, a limit of detection of ∼170 particles μL −1 (26 fM of the spike protein) is achieved in 15 min without the need of any pretreatment. As a proof of concept, the one-step thermophoretic assay is used to detect synthetic samples by spiking viral particles into oropharyngeal swabs with an accuracy of 100%. The simplicity, speed, and cost-effectiveness of this thermophoretic assay may expand the diagnostic tools for viral pathogens.

The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201805033.The rapid development of microfluidics technology has promoted new innovations in materials science, particularly by interacting with biological systems, based on precise manipulation of fluids and cells within microscale confinements. This article reviews the latest advances in microfluidics-based biomaterials and biodevices, highlighting some burgeoning areas such as functional biomaterials, cell manipulations, and flexible biodevices. These areas are interconnected not only in their basic principles, in that they all employ microfluidics to control the makeup and morphology of materials, but also unify at the ultimate goals in human healthcare. The challenges and future development trends in biological application are also presented. Microfluidics

In recent years, multi-modal entity linking (MEL) has garnered increasing attention in the research community due to its significance in numerous multi-modal applications. Video, as a popular means of information transmission, has become prevalent in people's daily lives. However, most existing MEL methods primarily focus on linking textual and visual mentions or offline videos's mentions to entities in multi-modal knowledge bases, with limited efforts devoted to linking mentions within online video content. In this paper, we propose a task called Online Video Entity Linking (OVEL), aiming to establish connections between mentions in online videos and a knowledge base with high accuracy and timeliness. To facilitate the research works of OVEL, we specifically concentrate on live delivery scenarios and construct a live delivery entity linking dataset called LIVE. Besides, we propose an evaluation metric that considers timelessness, robustness, and accuracy. Furthermore, to effectively handle OVEL task, we leverage a memory block managed by a Large Language Model and retrieve entity candidates from the knowledge base to augment LLM performance on memory management. The experimental results prove the effectiveness and efficiency of our method.

Immunoassays whose readouts rely on chemiluminescence are increasingly useful for a broad range of analytical applications, but they are rarely made into point-of-care (POC) format because of the complex reagents required (some reagents have to be stored in low temperatures, and some reagents have to be freshly made right before the assay). This study reports a self-contained chemiluminescent lateral flow assay (CLFA), which prestores all necessary reagents. This CLFA contains three parts: the normal lateral flow assay (LFA) strip, the chemiluminescence substrate pad, and the polycarbonate (PC) holder. On the LFA strip, we simultaneously labeled horseradish peroxidase (HRP) and antibody on the gold nanoparticles (AuNPs) for the conjugate pad. For the substrate pad, we used sodium perborate as the oxidant and lyophilized the chemiluminescence substrate on the glass fiber, which allows long-term storage. After the transfer of substrate from the substrate pad to the nitrocellulose (NC) membrane, we captured the chemiluminescence signal for the quantification of the targets. The HRP on the AuNPs can amplify the chemiluminescence signal efficiently. We used this CLFA system to detect both macromolecules and small molecules successfully. This self-contained and easily processable device is exceedingly appropriate for rapid detection and is a convenient platform for POC testing.

Microfluidic platforms capable of automated, rapid, sensitive, and quantitative detection of biomarkers from patient samples could make a major impact on clinical or point-of-care (POC) diagnosis. In this work, we realize an automated diagnostic platform composed of two main components: (1) a disposable, self-contained, and integrated microfluidic chip and (2) a portable instrument that carries out completely automated operations. To demonstrate its potential for real-world application, we use injection molding for mass fabrication of the main components of disposable microfluidic chips. The assembled three-layered chip with on-chip mechanical valves for fluid control consists of (1) a top silicone fluidic layer with embedded zigzag microchannels, reagent reservoirs and a negative pressure port, (2) a middle tinfoil layer with patterned antibody/antigen stripes, and (3) a bottom silicone substrate layer with waste reservoirs. The versatility of the microfluidics-based system is demonstrated by implementation of a chemiluminescence immunoassay for quantitative detection of C-reactive protein (CRP) and testosterone in real clinical samples. This lab-on-a-chip platform with features of quantitation, portability and automation provides a promising strategy for POC diagnosis.