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ADVANCED FUNCTIONAL MATERIALS · 2022 ·Vol. 32 ·期 48 ·2207879 · IF 19.924

Screening Prostate Cancer Cell-Derived Exosomal MicroRNA Expression with Photothermal-Driven Digital PCR

Lexiang Zhang,Wenzhao Li,Rokshana Parvin,XiaoChen Wang,Qihui Fan,Fangfu Ye

Exosomes are cell-derived extracellular vesicles which enclose genetic substances from their origin cells, offering a good source of biomarkers. Many efforts have been made to develop non-invasive exosome-based clinical diagnosis, which are urgently needed for prostate cancer, as traditional methods are criticized due to the inaccuracy and discomfort. In this study, a simple, universal process for genotyping of exosome-derived microRNAs using nanoparticles to capture exosomes and the novel photothermal droplet digital polymerase chain reaction (ddPCR) assay to detect target molecules is presented. To detect the target sensitively and simply, the smart ddPCR thermocycling of the agarose microcarriers can be controllably realized via embedding photothermal MXene and magnetic nanoparticles composite, and then irradiating with a homemade automated near-infrared control module. Duplex photothermal-driven ddPCR cooperating with dual TaqMan probes enabled simultaneously and quantitatively detecting copy numbers of prostate oncogenes microRNA-21-5p, microRNA-375-3p, and metastasis microRNA-574-3p along with the control microRNA-30a-5p within the extracted exosomes. The results show that the expression levels of these biomarkers in prostate cancer cell lines PC-3 and DU145 are 7–210 folds higher than those in healthy control cells HaCaT and HUVEC. Thus, it is believed that these versatile exosomal microRNA genotyping approaches are potentially valuable for diverse clinical applications.

CAS / MDL: 1310-73-2 127-09-3
研究领域: 癌症生物学 · 分子诊断 · 纳米技术 · 生物医学工程
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Journal of Innovative Optical Health Sciences · 2024 · IF 2.3

Machine learning-enhanced SERS for accurate azoospermia diagnosis via seminal plasma exosome analysis

Jiarui Wang,Shiyan Jiang,Jiaxin Shi,Jing Wang,Shengrong Du,Zufang Huang

Male infertility affects 10–15% of couples globally, with azoospermia — complete absence of sperm — accounting for 15% of cases. Traditional diagnostic methods for azoospermia are subjective and variable. This study presents a novel, noninvasive, and accurate diagnostic method using surface-enhanced Raman spectroscopy (SERS) combined with machine learning to analyze seminal plasma exosomes. Semen samples from healthy controls ( n = 3 2 ) and azoospermic patients ( n = 2 2 ) were collected, and their exosomal SERS spectra were obtained. Machine learning algorithms were employed to distinguish between the SERS profiles of healthy and azoospermic samples, achieving an impressive sensitivity of 99.61% and a specificity of 99.58%, thereby highlighting significant spectral differences. This integrated SERS and machine learning approach offers a sensitive, label-free, and objective diagnostic tool for early detection and monitoring of azoospermia, potentially enhancing clinical outcomes and patient management.

研究领域: 生殖医学 · 生物医学工程 · 分析化学 · 医疗健康中的机器学习
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Advanced Intelligent Systems · 2021 ·Vol. 3 ·期 4 ·2000090 · IF 0

Raman Spectroscopy Reveals Abnormal Changes in the Urine Composition of Prostate Cancer: An Application of an Intelligent Diagnostic Model with a Deep Learning Algorithm

Shengnan Chen,Heng Zhang,Xiangfei Yang,Xiaoguang Shao,Taihao Li,Na Chen,Zhenyi Chen,Wei Xue,Jiahua Pan,Shupeng Liu

Early diagnosis of prostate cancer (PCa) is always a great challenge in clinical practice, especially in distinguishing benign prostatic hyperplasia (BPH) from early cancer, due to the high similarity in pathology from the prostate-specific antigen (PSA) test and radiological detection. The conventional diagnostic methods are often less efficient in specificity and accuracy, leading to quite a few unnecessary biopsies. This work establishes a noninvasive diagnostic method for PCa by investigating urine samples using Raman spectroscopy and convolutional neural network (CNN) algorithm. The results of urine Raman spectra show the intensities of characteristic peaks for lipids, nucleic acids, and some amino acids are distinguishable between PCa and BPH, suggesting an abnormal metabolism caused by PCa, which can be detected by Raman spectroscopy. These data are then used to train an intelligent diagnostic model with CNN algorithm. The cross-validation results show the mean diagnostic accuracy, sensitivity, and specificity for PCa are 74.95%, 77.32%, and 72.46%, respectively. This noninvasive diagnostic method is a promising method for the early diagnosis of PCa, and the idea of using urine Raman spectroscopy with deep learning techniques for diagnosing PCa provides a reference for the application of artificial intelligence in the field of clinical medicine research.

研究领域: 肿瘤学 · 泌尿科学 · 分子诊断学 · 转化医学 · 生物光子学 · 临床化学 · 人工智能医学
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VIEW · 2024 · IF 9.7

CRISPR/Cas12a-loaded intelligent DNA hydrogel for universal and ultrasensitive exosome assay

Jie Luo,Binpan Wang,Xiaoqi Tang,Ping Huang,Sha Yang,Shuang Zhao,Shuang Xie,Qiaofeng Li,Kai Chang,Ming Chen

Tumor-derived exosomes are crucial for early non-invasive and accurate tumor diagnosis in clinical diagnostics. The development of highly sensitive, simple, and intuitive exosome assays has sparked a research upsurge in clinical diagnostics. Here, we develop a bio-responsive intelligent DNA hydrogel loaded with CRISPR/Cas12a for universal and ultrasensitive detection of the exosomes. The aptamer serves as the target response unit and switch, competitively disintegrating the region of the DNA linkers and then Cas12a/crRNA was released and activated, resulting in a high fluorescent intensity for exosome detection at the detection limit of 119 particles/μL. Moreover, a constructed colorimetric tube is made by loading a colorimetric filter membrane on the tube lid and intelligent DNA hydrogel on the tube bottom, which enables one-pot portable colorimetric detection. Without the need for laboratory instruments and professionals, this strategy allows for naked eye detection with limit of detection as low as 10 4 particles/μL, and shows great applicability in distinguishing between healthy individuals, pretreatment patients, and post-treatment patients after obtaining a testable analyte. In this study, an ultrasensitive detection platform for exosomes that enables one-step sensing and dual signal output was introduced. The findings here suggest that this platform is a promising tool for the application of liquid biopsy based on exosomes in clinical diagnosis.

CAS / MDL: 7647-14-5 50-99-7
研究领域: 生物技术 · 分子生物学 · 临床诊断 · 纳米技术 · 癌症研究
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Advanced Science · 2022 ·Vol. 9 ·期 18 ·2104463 · IF 17.521

Noninvasive and Individual-Centered Monitoring of Uric Acid for Precaution of Hyperuricemia via Optical Supramolecular Sensing

Yaping Zhang,Huijuan Yu,Shiwei Chai,Xin Chai,Luyao Wang,Wen-Chao Geng,Juan-Juan Li,Yu-Xin Yue,Dong-Sheng Guo,Yuefei Wang

Characterized by an excessively increased uric acid (UA) level in serum, hyperuricemia induces gout and also poses a great threat to renal and cardiovascular systems. It is urgent and meaningful to perform early warning by noninvasive diagnosis, thus conducing to blockage of disease aggravation. Here, guanidinocalix[5]arene (GC5A) is successfully identified from the self-built macrocyclic library to specifically monitor UA from urine by the indicator displacement assay. UA is strongly bound to GC5A at micromolar-level, while simultaneously excluding fluorescein (Fl) from the GC5A·Fl complex in the “switch-on” mode. This method successfully differentiates patients with hyperuricemia from volunteers except for those with kidney dysfunction and targets a volunteer at high risk of hyperuricemia. In order to meet the trend from hospital-centered to individual-centered testing, visual detection of UA is studied through a smartphone equipped with a color-scanning feature, whose adaptability and feasibility are demonstrated in sensing UA from authentic urine, leading to a promising method in family-centered healthcare style. A high-throughput and visual detection method is provided here for alarming hyperuricemic by noninvasive diagnosis.

CAS / MDL: 121-44-8
研究领域: 分析化学 · 生物医学工程 · 医疗技术 · 分子传感
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BIOCONJUGATE CHEMISTRY · 2024 · IF 4

Fibronectin-Targeting Dual-Modal MR/NIRF Imaging Contrast Agents for Diagnosis of Gastric Cancer and Peritoneal Metastasis

Ningxin Yang,Yuelin Huang,Xiaoyu Wang,Dengbin Wang,Defan Yao,Gang Ren

The prevalence and fatality rates of gastric cancer (GC) remain elevated, with advanced stages presenting a grim prognosis. Noninvasive diagnosis of GC cancer often proves challenging until the disease has progressed to an advanced stage or metastasized. Initially, the level of fibronectin (FN) in cancer-associated fibroblasts (CAFs) of GC was at least 3.7 times higher than that in normal fibroblasts. Herein, two FN-targeting magnetic resonance/near-infrared fluorescence (MR/NIRF) imaging contrast agents were developed to detect GC and peritoneal metastasis noninvasively. The probes CREKA-Cy7-(Gd-DOTA) and CREKA-Cy7-(Gd-DOTA)3 demonstrated significant FN-targeting capability (with dissociation constants of 1.0 and 2.1 mM) and effective MR imaging performance (with proton relaxivity values of 9.66 and 27.44 mM–1 s–1 at 9.4 T, 37 °C). In vivo imaging revealed a high signal-to-noise ratio and successful visualization of GC metastasis using NIRF imaging as well as successful tumor detection in MR imaging. Therefore, this study highlights the potential of FN-targeting probes for GC diagnosis and aids in the advancement of new diagnostic strategies for the clinical detection of GC.

研究领域: 医学影像学 · 肿瘤学 · 分子生物学
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BIOSENSORS & BIOELECTRONICS · 2023 · IF 12.6

Versatile sweat bioanalysis on demand with hydrogel-programmed wearables

Yichen Chen,Biao Ma,Yinxiu Zuo,Gangsheng Chen,Qing Hao,Chao Zhao,Hong Liu

Wearable sweat bioanalysis is promising for non-invasive diagnostics of diseases. However, collection of representative sweat samples without disturbing daily life and wearable bioanalysis of targets that are clinically significant are still challenging. In this work, we report on a versatile method for the sweat bioanalysis. The method is based on a thermoresponsive hydrogel which can imperceptibly absorb slowly secreted sweat without stimulation such as heat or sport exercise. The wearable bioanalysis is accomplished by programmed electric heating of hydrogel modules to 42°C to release absorbed sweat or preloaded reagents into a microfluidic detection channel. Using our method, not only one-step detection of glucose but also multi-step immunoassay of cortisol is accomplished within 1 h, even at a very low sweat rate. Our test results are also compared with those obtained with conventional blood samples and stimulated sweat samples to evaluate the applicability of our method to non-invasive clinical practice.

研究领域: 生物医学工程 · 分析化学 · 可穿戴技术 · 医学诊断
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ACS Sensors · 2022 · IF 9.618

Artificially Intelligent Olfaction for Fast and Noninvasive Diagnosis of Bladder Cancer from Urine

Yingying Jian,Nan Zhang,Taoping Liu,Yujin Zhu,Di Wang,Hao Dong,Lihao Guo,Danyao Qu,Xue Jiang,Tao Du,Youbin Zheng,Miaomiao Yuan,Xuemei Fu,Jinmei Liu,Wei Dou,Fang Niu,Ruizhi Ning,Guangjian Zhang,Jinhai Fan,Hossam Haick,Weiwei Wu

Globally, bladder cancer (BLC) is one of the most common cancers and has a high recurrence and mortality rate. Current clinical diagnostic approaches are either invasive or inaccurate. Here, we report on a cost-efficient, artificially intelligent chemiresistive sensor array made of polyaniline (PANI) derivatives that can noninvasively diagnose BLC at an early stage and maintain postoperative surveillance through ″smelling″ clinical urine samples at room temperature. In clinical trials, 18 healthy controls and 76 BLC patients (60 and 16 at early and advanced stages, respectively) are assessed by the artificial olfactory system. With the assistance of a support vector machine (SVM), very high sensitivity and accuracy from healthy controls are achieved, exceeding those obtained by the current techniques in practice. In addition, the recurrences of both early and advanced stages are diagnosed well, with the effect of confounding factors on the performance of the artificial olfactory system found to have a negligible influence on the diagnostic performance. Overall, this study contributes a novel, noninvasive, easy-to-use, inexpensive, real-time, accurate method for urine disease diagnosis, which can be useful for personalized care/diagnosis and postoperative surveillance, resulting in saving more lives.

研究领域: 医学诊断 · 生物医学工程 · 人工智能 · 癌症研究
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MICROCHIMICA ACTA · 2021 ·Vol. 188 ·期 1 ·1-9 · IF 5.833

Determination of plasma β-amyloids by rolling circle amplification chemiluminescent immunoassay for noninvasive diagnosis of Alzheimer’s disease

Wang Danhua,Dai Yibei,Wang Xuchu,Yu Pan,Qu Shufang,Liu Zhenping,Cao Ying,Zhang Lingyu,Ping Ying,Liu Weiwei,Tao Zhihua

A rolling circle amplification chemiluminescence immunoassay (RCA-CLIA) was developed for precise quantitation of Aβ in plasma. Capture antibodies conjugated with magnetic beads and detection antibodies with collateral single-stranded DNA (ssDNA) were bound to Aβ42/Aβ40 antigens to form a typical double-antibody sandwich structure. The RCA reaction was triggered by the addition of ssDNA, which generated products with a large number of sites for the binding of acridinium ester (AE)–labeled detection probes, thereby realizing the purpose of the amplification. The RCA-CLIA method had higher sensitivity than conventional CLIA without loss of specificity. Under optimum conditions, the linear range of Aβ42 and Aβ40 detection was 3.9–140 pg/mL and 3.9–180 pg/mL, respectively, with corresponding low detection limits of 1.99 pg/mL and 3.14 pg/mL, respectively. Plasma Aβ42 and Aβ40 were detected in the blood of 21 AD patients and 22 healthy people, wherein this ratio could significantly distinguish AD patients from healthy individuals with a sensitivity of 90.48% and specificity of 63.64% for a cutoff value of 154. The Aβ42/Aβ40 ratio of plasma acts as an accurate indicator for AD diagnosis; therefore, detection of plasma Aβ using the RCA-CLIA exhibits great potential in noninvasive diagnosis and progressive assessment of AD.

CAS / MDL: 1633-78-9
研究领域: 医学诊断 · 神经退行性疾病 · 生物技术
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2025 · IF 3.8

Carbon quantum dot-aptamer/MoS2 nanosheet fluorescent sensor for ultrasensitive, noninvasive cortisol detection

Chen Rong,Wang Mingyu,Nie Hailiang,Zhang Jinku,Yan Hongyuan

This work presents the development of a highly sensitive, selective, and efficient aptamer-based fluorescent sensor for detecting cortisol in human urine. Carbon quantum dots-nucleic acid aptamer (CQDs-Apt) synthesized with excellent photoluminescent properties and stability, were selected as the fluorescent probe. In the presence of MoS 2 -NSs, CQDs-Apt adsorbed onto the surface of MoS 2 -NSs via electrostatic and π-π interactions, leading to strong and rapid fluorescence quenching due to static quenching mechanism between them. The CQDs-Apt/MoS 2 -NSs complex can be employed as a “turn-on” fluorescent sensor for cortisol. Upon the addition of cortisol to the CQDs-Apt/MoS 2 -NSs sensor, the aptamer specifically binds to cortisol, thereby weakening the interaction between CQDs-Apt and MoS 2 -NSs. This results in the desorption of CDs-Apt from the surface of MoS 2 -NSs and the recovery of the fluorescence signal. Under optimized conditions, the CQDs-Apt/MoS 2 -NSs sensor exhibits a linear response to cortisol concentration (1–500 ng/mL) with a detection limit of 0.3 ng/mL. Furthermore, the sensor demonstrated excellent stability, high accuracy (92.0% to 97.7%), and superior precision (RSD ≤ 3.5%). This sensor has achieved a sensitive, rapid and efficient response to cortisol, and been successfully utilized for the detection of cortisol in human urine, demonstrating its potential for clinical cortisol detection.

研究领域: 分析化学 · 纳米技术 · 生物传感器 · 临床诊断 · 环境监测
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Materials Today Advances · 2025 · IF 8

Polythioctic acid-driven biomemristor for efficient sweat pH monitoring

Zijun Xu,Ruiming Liu,Bai Sun,Xiaosen Pan,Zelin Cao,Kaikai Gao,Yu Cui,Hongbin Zhao,Hao Sun,Qiang Lu,Yi Lyu,Fenggang Ren

Memristors have attracted widespread attention in the fields of brain-like chips and neuromorphic computing due to their parallel computing capabilities and characteristics to simulate neural synapses. However, the application of memristor in healthcare monitoring and diagnosis has not yet been well developed, which may delay the progress of smart healthcare services empowered by artificial intelligence (AI). Herein, it was demonstrated a pH-responsive memristor with an Ag/Poly(diethylene glycol ester thioctic acid)-Li/FTO structure, which shows excellent resistance switching behaviors with self-rectifying characteristics. Further, it was found the device can achieve precise acid-base discrimination through synergistic mechanisms involving the cationic conduction properties of the C-S bond in Poly(diethylene glycol ester thioctic acid) and the uniqueness of the metal-oxygen coordination bond. Accurate solution pH determination can be accomplished within 3 min via analysis of the time-dependent ΔI F-R parameter, defined as the different between forward peak and reverse currents. Finally, the device was successfully applied to determine sweat pH levels, demonstrating the potential of the pH-responsive memristor in monitoring health status through sweat. Therefore, this work provides new insights for non-invasive preliminary diagnosis and early warning of metabolic diseases such as diabetes, which effectively promotes the rapid development of smart wearable medical devices.

研究领域: 生物医学工程 · 神经形态计算 · 可穿戴传感器 · 健康监测 · 材料科学
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Advanced Healthcare Materials · 2025 · IF 9.6

Aqueous Gallium-Doped Copper Indium Selenide Quantum Dots for Non-Invasive Severity Grading of Traumatic Brain Injury

Xiao Sun,Wanru Tian,Xin Zhao,Xuan Cheng,Yao Li,Qiye Wang,Weichen Li,Peisen Zhang,Mingxia Jiao,Xiliang Luo

Traumatic brain injury (TBI) represents a substantial global health challenge, yet current diagnostic tools, such as CT and MRI, despite providing anatomical detail, have limitations in assessing injury severity, monitoring progression, and guiding personalized treatments. Herein, an aqueous phase-synthesized gallium-doped copper indium selenide quantum dot (QD) probe designed for grading TBI severity is introduced. The doping of gallium ions into the semiconductor core largely restrained the nonradiative recombination rate, thereby significantly enhancing the near-infrared emission of the QDs. Surface modification strategies further improve QD stability and biocompatibility, ensuring high-sensitivity imaging in vivo. In mouse models with varying TBI severities, intravenous administration of Ga-doped QDs, combined with advanced imaging protocols and data analysis, achieved objective grading of injury severity through quantitative analysis of fluorescence signal intensity and distribution, demonstrating a remarkable correlation between QD-derived signals and neuropathological severity. This grading result is further verified by a series of behavioral tests of the corresponding TBI mice. This QD-based imaging strategy offers a sensitive and objective tool for TBI assessment, enabling precise grading and dynamic monitoring, thereby improving clinical decision-making. This innovation complements existing diagnostics and has transformative potential for optimizing TBI management and patient outcomes, especially in resource-limited settings.

研究领域: 生物医学成像 · 纳米医学 · 神经创伤 · 材料科学 · 诊断工具
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