Pub Date : 2025-12-08DOI: 10.1016/j.aca.2025.344987
Kalman Toth, Thomas P.J. Linsinger
Accurate estimation of the uncertainty of stability is crucial for certified reference materials (CRMs), as it forms a component of the overall uncertainty budget. In case of between-unit heterogeneity, results obtained on the same unit of a CRM are not independent which leads to a bias in the estimated uncertainty of stability when used ordinary least squares. This bias depends on the ratio of between-unit heterogeneity to method repeatability and the number of replicate analyses performed per unit and can reach nearly 50 % for as few as three replicates per unit. A study on actual certified values shows that this bias can influence the certified values. The study shows that employing linear mixed-effects models (LME) with restricted maximum likelihood (REML) for parameter estimation provides consistent estimate of uncertainty of stability, even in the presence of significant between-unit heterogeneity. Simpler, alternative approaches for specific scenarios, such as well-balanced datasets are also provided.
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Breast cancer is one of the most significant malignancies worldwide, representing one out of every eight cancers diagnosed in women and affecting one in four women across all ages. Early diagnosis is essential for improving survival and overall quality of life, yet limitations such as the lack of affordable traditional tests and technological or biological barriers often delay timely detection. Extracellular vesicles (EVs), which facilitate information exchange among cancer cells, hold strong potential as primary biomarker for cancer detection. However, the lack of simple, reliable, and reproducible platforms for EV isolation and detection remains a major challenge.
Results
In this study, we focus on the selective isolation of EVs cultured and collected on a microfluidic chip engineered to mimic the cancer microenvironment, using molecularly imprinted cryogel membranes. Optimal conditions for EV adsorption onto these membranes were systematically identified in a batch system using a rotator. The resulting cryogel-based platform demonstrated a high adsorption capacity of 1075 particles per gram of cryogel at pH 5.0. The membranes also showed excellent regeneration performance following EV desorption with 1 M NaCl, supporting sustained operational stability. Strong alignment with the Langmuir adsorption model and validation through HPLC analyses provide both mechanistic insight and analytical confidence, positioning this approach as a robust and reproducible alternative to conventional EV isolation strategies.
Significance
Overall, these findings introduce a novel, scalable cryogel-based platform for EV purification, offering high reliability, quantifiability, and reusability. The system’s solid analytical performance and compatibility with downstream processing highlight its broad potential in biochemical, diagnostic, and EV-based research and technologies.
乳腺癌是世界上最严重的恶性肿瘤之一，每8个女性确诊癌症中就有1个患有乳腺癌，在所有年龄段的女性中，每4个女性中就有1个患有乳腺癌。早期诊断对于改善生存和整体生活质量至关重要，但缺乏负担得起的传统检测以及技术或生物障碍等限制往往会延误及时发现。细胞外囊泡（EVs）促进癌细胞之间的信息交换，作为癌症检测的主要生物标志物具有很强的潜力。然而，缺乏简单、可靠和可重复的EV隔离和检测平台仍然是一个主要挑战。结果在模拟肿瘤微环境的微流控芯片上，利用分子印迹低温凝胶膜对体外培养和收集的ev进行了选择性分离。利用旋转器在间歇系统中系统地确定了EV吸附在这些膜上的最佳条件。结果表明，在pH 5.0下，每克低温凝胶的吸附量为1075个颗粒。在1 M NaCl脱附EV后，膜也表现出良好的再生性能，支持持续的运行稳定性。与Langmuir吸附模型高度一致，并通过HPLC分析验证，提供了机制洞察力和分析可信度，将该方法定位为传统EV分离策略的可靠且可重复的替代方法。总体而言，这些发现为EV净化提供了一种新颖的、可扩展的基于低温的平台，具有高可靠性、可量化性和可重用性。该系统可靠的分析性能和与下游处理的兼容性突出了其在生化、诊断和基于ev的研究和技术方面的广泛潜力。
{"title":"Isolation and adsorption of extracellular vesicles using molecularly imprinted cryogel membranes","authors":"Almaysh Haidar Rizqullah , Eylul Gulsen Yilmaz , Yeşeren Saylan","doi":"10.1016/j.aca.2025.344993","DOIUrl":"10.1016/j.aca.2025.344993","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is one of the most significant malignancies worldwide, representing one out of every eight cancers diagnosed in women and affecting one in four women across all ages. Early diagnosis is essential for improving survival and overall quality of life, yet limitations such as the lack of affordable traditional tests and technological or biological barriers often delay timely detection. Extracellular vesicles (EVs), which facilitate information exchange among cancer cells, hold strong potential as primary biomarker for cancer detection. However, the lack of simple, reliable, and reproducible platforms for EV isolation and detection remains a major challenge.</div></div><div><h3>Results</h3><div>In this study, we focus on the selective isolation of EVs cultured and collected on a microfluidic chip engineered to mimic the cancer microenvironment, using molecularly imprinted cryogel membranes. Optimal conditions for EV adsorption onto these membranes were systematically identified in a batch system using a rotator. The resulting cryogel-based platform demonstrated a high adsorption capacity of 1075 particles per gram of cryogel at pH 5.0. The membranes also showed excellent regeneration performance following EV desorption with 1 M NaCl, supporting sustained operational stability. Strong alignment with the Langmuir adsorption model and validation through HPLC analyses provide both mechanistic insight and analytical confidence, positioning this approach as a robust and reproducible alternative to conventional EV isolation strategies.</div></div><div><h3>Significance</h3><div>Overall, these findings introduce a novel, scalable cryogel-based platform for EV purification, offering high reliability, quantifiability, and reusability. The system’s solid analytical performance and compatibility with downstream processing highlight its broad potential in biochemical, diagnostic, and EV-based research and technologies.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1385 ","pages":"Article 344993"},"PeriodicalIF":6.0,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Methamphetamine (MAMP) is an arousing addictive drug and its close tracing in human biofluids or suspected shipments to diagnose poisoning or aid in its induced death investigation is legally important. This study presents a rapid and visual measurement of MAMP based on a novel platform involving the electrochromic properties of polyaniline (PANI). PANI film has been electrochemically deposited on the surface of indium tin oxide (ITO) to achieve the desired electrochromic behavior and also embed a suitable platform for the attachment of the aptamer (Apt) as the bioreceptor for MAMP with high affinity.
Results
For the first time, an electrochromic aptasensing interface, referred to as the Apta-Chip, has been created by combining two electrochemical and optical methods for measuring MAMP. The developed Apta-Chip based on the PANI/ITO surface displays a wide range of colors at close potentials, serving as an electrochromic optical detector. The presence of MAMP on the embedded surface increases the resistance in the circuit, affecting the PANI oxidation states, creating a different electrochromic response that depends on MAMP concentration. Thereby, the optical detection of MAMP is performed with the naked eye, yielding highly favorable outcomes for MAMP monitoring in human serum, urine and saliva samples, as biofluid samples. Compared to conventional MAMP sensors, the proposed Apta-Chip provides a multicolor behavior with vivid tonality from dark blue, green and dark yellow for different MAMP concentrations.
Significance
The molecular dynamics (MD) simulation has been carried out to predict how Apt links to MAMP visually. Additionally, the greenness of the applied methodology has been well evaluated by two international criteria based on the green chemistry principles. The developed Apta-Chip holds promise to reasonably distinguish MAMP with the naked eye in real clinical or street narcotic samples.
{"title":"A scalable electrochromic aptasensing interface as a highly selective Apta-Chip for visual detection of methamphetamine","authors":"Faezeh Shahdost-Fard , Zeynab Khorablou , Habib Razmi , Maliheh Arhami","doi":"10.1016/j.aca.2025.344970","DOIUrl":"10.1016/j.aca.2025.344970","url":null,"abstract":"<div><h3>Background</h3><div>Methamphetamine (MAMP) is an arousing addictive drug and its close tracing in human biofluids or suspected shipments to diagnose poisoning or aid in its induced death investigation is legally important. This study presents a rapid and visual measurement of MAMP based on a novel platform involving the electrochromic properties of polyaniline (PANI). PANI film has been electrochemically deposited on the surface of indium tin oxide (ITO) to achieve the desired electrochromic behavior and also embed a suitable platform for the attachment of the aptamer (Apt) as the bioreceptor for MAMP with high affinity.</div></div><div><h3>Results</h3><div>For the first time, an electrochromic aptasensing interface, referred to as the Apta-Chip, has been created by combining two electrochemical and optical methods for measuring MAMP. The developed Apta-Chip based on the PANI/ITO surface displays a wide range of colors at close potentials, serving as an electrochromic optical detector. The presence of MAMP on the embedded surface increases the resistance in the circuit, affecting the PANI oxidation states, creating a different electrochromic response that depends on MAMP concentration. Thereby, the optical detection of MAMP is performed with the naked eye, yielding highly favorable outcomes for MAMP monitoring in human serum, urine and saliva samples, as biofluid samples. Compared to conventional MAMP sensors, the proposed Apta-Chip provides a multicolor behavior with vivid tonality from dark blue, green and dark yellow for different MAMP concentrations.</div></div><div><h3>Significance</h3><div>The molecular dynamics (MD) simulation has been carried out to predict how Apt links to MAMP visually. Additionally, the greenness of the applied methodology has been well evaluated by two international criteria based on the green chemistry principles. The developed Apta-Chip holds promise to reasonably distinguish MAMP with the naked eye in real clinical or street narcotic samples.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1385 ","pages":"Article 344970"},"PeriodicalIF":6.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-06DOI: 10.1016/j.aca.2025.344994
Xiao Ma , Huimin Ren , Li Zhao , Xiaojie Guo , Jiran Zhang , Juan Liu , Xiaona Wang , Mengyao Wang , Yifu Lu , Shilu Tong , Hongyang Cui , Hong Chang , Yu'e Cha , Song Tang , Xiaoming Shi
Background
Steroid hormones (SHs) in human urine are critical for understanding physiological processes, but their analysis is challenged by intricate urine matrices and diverse SHs physicochemical properties. Existing methods often lack sensitivity, throughput, or comprehensiveness for simultaneous qualitative and quantitative profiling. Thus, there is a need for a state-of-the-art, ultra-sensitive, high-throughput method to comprehensively and simultaneously characterize urinary SHs.
Results
The improved liquid-liquid extraction (LLE) and ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method, developed by optimizing mass spectrum parameters and pretreatment conditions to address urine matrix complexity and SHs diversity, identified 133 SHs and quantified 103. The improved experimental protocol was as follows: sample volume, 1 mL; extraction solvent, methyl tert-butyl ether/ethyl acetate (MTBE/EtAc, 1/1, v/v); solvent volume, 2 mL; extraction times, 2; pH, 9; enzyme activity, 1700 U/mL; eluent A, water; eluent B, methanol. Post-extraction samples were analyzed using UPLC-QqQ-MS/MS, with quantification of method-validated SHs reliably performed through internal standards (ISs) calibration. Validated metrics included excellent linearity (R2 > 0.990, 1–500 ng/mL), the method detection/quantitation limit (MDL, 0.003–0.740 ng/mL; MQL, 0.01–2.465 ng/mL), matrix effects (ME, −0.46 %–46.56 %), recoveries (72.31 %–129.80 %), and precision/stability (RSDs <20 %). Applied to 76 elderly adults, it revealed gender-specific temporal variations, with significant 5-month declines in androgens and glucocorticoids.
Significance
This method enables comprehensive, sensitive urinary SHs profiling, offering a powerful tool for in-depth research on elderly hormonal dynamics. Its ability to capture gender and temporal variations enhances understanding of age-related hormonal changes.
{"title":"Development of a high-throughput LLE-UPLC-QqQ-MS/MS method and comprehensive profiling of urinary steroid hormones in Chinese elderly adults","authors":"Xiao Ma , Huimin Ren , Li Zhao , Xiaojie Guo , Jiran Zhang , Juan Liu , Xiaona Wang , Mengyao Wang , Yifu Lu , Shilu Tong , Hongyang Cui , Hong Chang , Yu'e Cha , Song Tang , Xiaoming Shi","doi":"10.1016/j.aca.2025.344994","DOIUrl":"10.1016/j.aca.2025.344994","url":null,"abstract":"<div><h3>Background</h3><div>Steroid hormones (SHs) in human urine are critical for understanding physiological processes, but their analysis is challenged by intricate urine matrices and diverse SHs physicochemical properties. Existing methods often lack sensitivity, throughput, or comprehensiveness for simultaneous qualitative and quantitative profiling. Thus, there is a need for a state-of-the-art, ultra-sensitive, high-throughput method to comprehensively and simultaneously characterize urinary SHs.</div></div><div><h3>Results</h3><div>The improved liquid-liquid extraction (LLE) and ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method, developed by optimizing mass spectrum parameters and pretreatment conditions to address urine matrix complexity and SHs diversity, identified 133 SHs and quantified 103. The improved experimental protocol was as follows: sample volume, 1 mL; extraction solvent, methyl <em>tert</em>-butyl ether/ethyl acetate (MTBE/EtAc, 1/1, v/v); solvent volume, 2 mL; extraction times, 2; pH, 9; enzyme activity, 1700 U/mL; eluent A, water; eluent B, methanol. Post-extraction samples were analyzed using UPLC-QqQ-MS/MS, with quantification of method-validated SHs reliably performed through internal standards (ISs) calibration. Validated metrics included excellent linearity (R<sup>2</sup> > 0.990, 1–500 ng/mL), the method detection/quantitation limit (MDL, 0.003–0.740 ng/mL; MQL, 0.01–2.465 ng/mL), matrix effects (ME, −0.46 %–46.56 %), recoveries (72.31 %–129.80 %), and precision/stability (RSDs <20 %). Applied to 76 elderly adults, it revealed gender-specific temporal variations, with significant 5-month declines in androgens and glucocorticoids.</div></div><div><h3>Significance</h3><div>This method enables comprehensive, sensitive urinary SHs profiling, offering a powerful tool for in-depth research on elderly hormonal dynamics. Its ability to capture gender and temporal variations enhances understanding of age-related hormonal changes.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1385 ","pages":"Article 344994"},"PeriodicalIF":6.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-06DOI: 10.1016/j.aca.2025.344992
Chowdhury Kamrul Hasan , Fazria Tanjum , Parvez Mahbub
Background
Screening organic peroxide explosives (OPEs) such as hexamethylene triperoxide diamine (HMTD), methyl ethyl ketone peroxide (MEKP), and triacetone triperoxide (TATP) from ambient interferents (e.g. household H2O2, perfume, and nail polish remover) at the security heightened areas has been a significant challenge for the security authorities worldwide. The present research aims to overcome this challenge for the first time by integrating a UV LED based micro-photoreactor with an in-house developed stabilising reagent to screen the OPEs from household H2O2.
Results
Since OPEs along with H2O2 upon their exposure to UV radiation spontaneously generate peroxy moieties and radicals, the aqueous stabilising reagent, composed of dimethyl sulfoxide (100 mM), sodium thiosulfate (100 μM), and cobalt chloride (10 μM), was developed to effectively stabilise these peroxy moieties. We confirmed this stabilising phenomenon by investigating GC-MS profile of OPE samples with/without activating the micro-photoreactor, revealing controlled stabilisation of photodegradation products from MEKP and significant stabilisation of those from HMTD and TATP. Notably, we observed how the swabs of OPEs from skin surfaces, when immersed in the screening reagent prior to their transfer via the active micro-photoreactor (driven with radiometrically optimised parameters e.g., 800 KHz, 3.3 V, and 0.13 Amp), enabled flow injection analysis-chemiluminescence (FIA-CL) signals remarkably distinguishable from that of H2O2 within 10 s.
Significance and novelty
We present a novel screening mechanism of OPEs from household products using in-house developed and radiometrically characterised UVLED based portable micro-photoreactors as well as stabilising reagent to stabilise the photodegradation of OPEs. This study affords selective and ultra-trace level of screening of HMTD (0.12 μM, n = 3, RSD 6 %), MEKP (0.08 μM, n = 3, RSD 6 %) and TATP (0.16 μM, n = 3, RSD 7 %) from H2O2, highlighting its potential for real-world explosive screening applications in security heightened settings in a rapid, safe, and effective manner.
背景：在安全警戒区域筛选有机过氧化物炸药（OPEs），如六亚甲基三过氧化物二胺（HMTD）、甲基乙基过氧化物酮（MEKP）和三过氧化物三丙酮（TATP）免受环境干扰（例如家用H2O2、香水和洗甲水）一直是世界各地安全当局面临的重大挑战。目前的研究旨在首次克服这一挑战，将基于UV LED的微光反应器与内部开发的稳定试剂集成在一起，以筛选家用H2O2中的OPEs。结果由于OPEs与H2O2在紫外线照射下会自发产生过氧基团和自由基，因此制备了由二甲亚砜（100 mM）、硫代硫酸钠（100 μM）和氯化钴（10 μM）组成的水稳定剂，可以有效地稳定这些过氧基团。我们通过研究有/没有激活微光反应器的OPE样品的GC-MS谱证实了这种稳定现象，揭示了MEKP光降解产物的可控稳定性以及HMTD和TATP的显著稳定性。值得注意的是，我们观察到皮肤表面的OPEs，在通过有源微光反应器（由辐射优化参数驱动，例如800 KHz， 3.3 V和0.13安培）转移之前浸泡在筛选试剂中，如何在10秒内使流动注射分析-化学发光（FIA-CL）信号与H2O2显著区分。我们提出了一种从家用产品中筛选OPEs的新机制，该机制使用了自主开发的基于UVLED的便携式微光反应器和稳定试剂来稳定OPEs的光降解。本研究提供了H2O2对HMTD （0.12 μM, n = 3, RSD 6%）、MEKP （0.08 μM, n = 3, RSD 6%）和TATP （0.16 μM, n = 3, RSD 7%）的选择性和超痕量筛选，突出了其在现实世界中快速、安全、有效地筛选爆炸物的潜力。
{"title":"Radiometrically characterised ultraviolet light-emitting diode (UVLED) based micro-photoreactors for rapid, safe and portable screening of organic peroxide explosives","authors":"Chowdhury Kamrul Hasan , Fazria Tanjum , Parvez Mahbub","doi":"10.1016/j.aca.2025.344992","DOIUrl":"10.1016/j.aca.2025.344992","url":null,"abstract":"<div><h3>Background</h3><div>Screening organic peroxide explosives (OPEs) such as hexamethylene triperoxide diamine (HMTD), methyl ethyl ketone peroxide (MEKP), and triacetone triperoxide (TATP) from ambient interferents (e.g. household H<sub>2</sub>O<sub>2</sub>, perfume, and nail polish remover) at the security heightened areas has been a significant challenge for the security authorities worldwide. The present research aims to overcome this challenge for the first time by integrating a UV LED based micro-photoreactor with an in-house developed stabilising reagent to screen the OPEs from household H<sub>2</sub>O<sub>2</sub>.</div></div><div><h3>Results</h3><div>Since OPEs along with H<sub>2</sub>O<sub>2</sub> upon their exposure to UV radiation spontaneously generate peroxy moieties and radicals, the aqueous stabilising reagent, composed of dimethyl sulfoxide (100 mM), sodium thiosulfate (100 μM), and cobalt chloride (10 μM), was developed to effectively stabilise these peroxy moieties. We confirmed this stabilising phenomenon by investigating GC-MS profile of OPE samples with/without activating the micro-photoreactor, revealing controlled stabilisation of photodegradation products from MEKP and significant stabilisation of those from HMTD and TATP. Notably, we observed how the swabs of OPEs from skin surfaces, when immersed in the screening reagent prior to their transfer via the active micro-photoreactor (driven with radiometrically optimised parameters e.g., 800 KHz, 3.3 V, and 0.13 Amp), enabled flow injection analysis-chemiluminescence (FIA-CL) signals remarkably distinguishable from that of H<sub>2</sub>O<sub>2</sub> within 10 s.</div></div><div><h3>Significance and novelty</h3><div>We present a novel screening mechanism of OPEs from household products using in-house developed and radiometrically characterised UVLED based portable micro-photoreactors as well as stabilising reagent to stabilise the photodegradation of OPEs. This study affords selective and ultra-trace level of screening of HMTD (0.12 μM, n = 3, RSD 6 %), MEKP (0.08 μM, n = 3, RSD 6 %) and TATP (0.16 μM, n = 3, RSD 7 %) from H<sub>2</sub>O<sub>2</sub>, highlighting its potential for real-world explosive screening applications in security heightened settings in a rapid, safe, and effective manner.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1385 ","pages":"Article 344992"},"PeriodicalIF":6.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.aca.2025.344988
Linlin Yang , Shiqiong Bai , Yuqing Nie , Yixuan Li , Fei Xin , Panpan Song , Na Gao , Liguo Ji , Lili Li , Guangjie He
Background
The development of fluorescent prodrugs based on bioorthogonal chemistry involves broadening the range of fluorophores that exhibit changes in fluorescence signals and the spatiotemporally regulated release of therapeutic agents upon biorthogonal ligation. However, there are still certain gaps including shallow tissue-penetrating and low drug release efficiency, which limit its application.
Results
Herein, we present a flexible and effective bioorthogonal scaffold that allows targeted medication release with simultaneous fluorescence emission when the targeting groups or prodrugs are conjugated. The scaffold consists of a tetrazine-caged methylene blue (MB-Tz), which serves as a dual switch for the activation of fluorophore and drug. Further encountering the TCO-caged molecular partner (TCO-RGD or TCO-Dox) triggers the NIR fluorescence reinstatement and simultaneously leads to spatiotemporal targeting and selective activation of prodrugs inside cancer cells. It was also demonstrated that bioorthogonal activation successfully inhibited tumor growth by controlled activation in vivo, with minimal systemic toxicity observed.
Significance
We envision that integration of fluorescence and bioorthogonal reactions will serve as a general small-molecule-based strategy for precisely targeted imaging and treatment in chemotherapy.
{"title":"Bioorthogonally activatable methylene blue platform for selective prodrug activation and fluorescent imaging in living systems","authors":"Linlin Yang , Shiqiong Bai , Yuqing Nie , Yixuan Li , Fei Xin , Panpan Song , Na Gao , Liguo Ji , Lili Li , Guangjie He","doi":"10.1016/j.aca.2025.344988","DOIUrl":"10.1016/j.aca.2025.344988","url":null,"abstract":"<div><h3>Background</h3><div>The development of fluorescent prodrugs based on bioorthogonal chemistry involves broadening the range of fluorophores that exhibit changes in fluorescence signals and the spatiotemporally regulated release of therapeutic agents upon biorthogonal ligation. However, there are still certain gaps including shallow tissue-penetrating and low drug release efficiency, which limit its application.</div></div><div><h3>Results</h3><div>Herein, we present a flexible and effective bioorthogonal scaffold that allows targeted medication release with simultaneous fluorescence emission when the targeting groups or prodrugs are conjugated. The scaffold consists of a tetrazine-caged methylene blue (MB-Tz), which serves as a dual switch for the activation of fluorophore and drug. Further encountering the TCO-caged molecular partner (TCO-RGD or TCO-Dox) triggers the NIR fluorescence reinstatement and simultaneously leads to spatiotemporal targeting and selective activation of prodrugs inside cancer cells. It was also demonstrated that bioorthogonal activation successfully inhibited tumor growth by controlled activation in vivo, with minimal systemic toxicity observed.</div></div><div><h3>Significance</h3><div>We envision that integration of fluorescence and bioorthogonal reactions will serve as a general small-molecule-based strategy for precisely targeted imaging and treatment in chemotherapy.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1384 ","pages":"Article 344988"},"PeriodicalIF":6.0,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.aca.2025.344989
Junru Zhang , Ying Chen , Junfei Liu , Wanwen Li , Liyong Niu , Qiguang Zhu
Background
Phenol is a key chemical intermediate and a common, toxic pollutant found in industrial wastewater from processes like coking and oil refining. Its leakage and discharge lead to significant contamination, posing a dual threat to ecological systems and human health, making its accurate, real-time monitoring paramount. Current detection methods have significant drawbacks. Chemical sensors can have long response times or insufficient accuracy. Standard optical methods like chromatography are cumbersome and ill-suited for rapid, on-site use. Simple UV–Vis spectroscopy is severely compromised by overlapping spectral interference and environmental instability in complex water samples.
Results
The strategy first leverages phenol's specific bromination to selectively eliminate its spectral signature. A custom dual-channel, variable-path (1–10 cm) system was built to capture this transformation, generating high-dimensional (3D) differential spectral matrices. This 3D data approach reduced the Mean Absolute Error (MAE) by 45.4 % compared to conventional 1D spectra (when using the same CNN model). For analysis, a novel Parallel Associative Neural Network (PSNN) was developed, which substantially outperformed a standard CNN by achieving a further 66.7 % reduction in MAE. This integrated strategy (3D + PSNN) yielded a final prediction error of 72.09 μg/L under laboratory conditions and an MAE of 172.9 μg/L in field tests against HPLC benchmarks.
Significance and novelty
This study presents a novel strategy integrating chemical selectivity, multidimensional optical sensing, and a custom Parallel Associative Neural Network (PSNN). The work provides a robust framework for developing highly selective and sensitive intelligent systems for on-line water quality monitoring. The practicality and stability of this integrated approach in complex environments were validated through temperature control experiments and field tests on real industrial wastewater.
{"title":"Synergistic integration of multidimensional differential spectroscopy and deep learning for robust phenol monitoring in complex industrial effluents","authors":"Junru Zhang , Ying Chen , Junfei Liu , Wanwen Li , Liyong Niu , Qiguang Zhu","doi":"10.1016/j.aca.2025.344989","DOIUrl":"10.1016/j.aca.2025.344989","url":null,"abstract":"<div><h3>Background</h3><div>Phenol is a key chemical intermediate and a common, toxic pollutant found in industrial wastewater from processes like coking and oil refining. Its leakage and discharge lead to significant contamination, posing a dual threat to ecological systems and human health, making its accurate, real-time monitoring paramount. Current detection methods have significant drawbacks. Chemical sensors can have long response times or insufficient accuracy. Standard optical methods like chromatography are cumbersome and ill-suited for rapid, on-site use. Simple UV–Vis spectroscopy is severely compromised by overlapping spectral interference and environmental instability in complex water samples.</div></div><div><h3>Results</h3><div>The strategy first leverages phenol's specific bromination to selectively eliminate its spectral signature. A custom dual-channel, variable-path (1–10 cm) system was built to capture this transformation, generating high-dimensional (3D) differential spectral matrices. This 3D data approach reduced the Mean Absolute Error (MAE) by 45.4 % compared to conventional 1D spectra (when using the same CNN model). For analysis, a novel Parallel Associative Neural Network (PSNN) was developed, which substantially outperformed a standard CNN by achieving a further 66.7 % reduction in MAE. This integrated strategy (3D + PSNN) yielded a final prediction error of 72.09 μg/L under laboratory conditions and an MAE of 172.9 μg/L in field tests against HPLC benchmarks.</div></div><div><h3>Significance and novelty</h3><div>This study presents a novel strategy integrating chemical selectivity, multidimensional optical sensing, and a custom Parallel Associative Neural Network (PSNN). The work provides a robust framework for developing highly selective and sensitive intelligent systems for on-line water quality monitoring. The practicality and stability of this integrated approach in complex environments were validated through temperature control experiments and field tests on real industrial wastewater.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1385 ","pages":"Article 344989"},"PeriodicalIF":6.0,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.aca.2025.344991
Ajith.B. Singh , Alavudeen Basha A , Arun Kumar U , Azath Mubarakali
Detection of refractive-index variations is fundamental for the development of next-generation optical sensing platforms capable of supporting future biomedical and chemical monitoring applications. Surface plasmon resonance (SPR) biosensing enables label-free, real-time detection but often faces limits in sensitivity, specificity, and stability. This work introduces a Kretschmann-based SPR biosensor that combines a multilayer stack of silver (Ag), gold (Au), and advanced functional materials including black phosphorus (BP), thallium bromide (TIBr) and formamidinium tin iodide (FASnI3). Hemoglobin is employed only as a model analyte to evaluate resonance shifts arising from bulk refractive-index variations within the range of 1.33–1.40 RIU. Numerical modeling using COMSOL Multiphysics and transfer matrix analysis showed performance metrics with sensitivities from 145 to 375°/RIU, figure of merit values up to 34.404, and quality factors between 6.450 and 7.917 within a refractive index range of 1.33–1.40 RIU. Optimization demonstrated that Ag thickness of 30–35 nm and functional layer thickness of 1.3–3.5 nm supports deep resonance dips with minimized ohmic losses. Electric-field distribution analysis demonstrates strong plasmon-induced field confinement near the sensing interface, with peak |E| intensities of approximately 2.4 × 105 V/m. Machine learning models predicted sensor behavior across different thicknesses and environmental conditions with coefficients of determination (R2) above 0.979 for layer thickness and 0.985 for refractive index. The resulting design offers high sensitivity refractive-index sensing, broad response range, and provide a foundation for future integration of biochemical functionalization toward selective biomarker detection.
{"title":"Multilayer Ag–Au–BP–TIBr–FASnI3 Kretschmann surface plasmon resonance biosensor for high sensitivity refractive index analysis: A computational and machine learning approach","authors":"Ajith.B. Singh , Alavudeen Basha A , Arun Kumar U , Azath Mubarakali","doi":"10.1016/j.aca.2025.344991","DOIUrl":"10.1016/j.aca.2025.344991","url":null,"abstract":"<div><div>Detection of refractive-index variations is fundamental for the development of next-generation optical sensing platforms capable of supporting future biomedical and chemical monitoring applications. Surface plasmon resonance (SPR) biosensing enables label-free, real-time detection but often faces limits in sensitivity, specificity, and stability. This work introduces a Kretschmann-based SPR biosensor that combines a multilayer stack of silver (Ag), gold (Au), and advanced functional materials including black phosphorus (BP), thallium bromide (TIBr) and formamidinium tin iodide (FASnI<sub>3</sub>). Hemoglobin is employed only as a model analyte to evaluate resonance shifts arising from bulk refractive-index variations within the range of 1.33–1.40 RIU. Numerical modeling using COMSOL Multiphysics and transfer matrix analysis showed performance metrics with sensitivities from 145 to 375°/RIU, figure of merit values up to 34.404, and quality factors between 6.450 and 7.917 within a refractive index range of 1.33–1.40 RIU. Optimization demonstrated that Ag thickness of 30–35 nm and functional layer thickness of 1.3–3.5 nm supports deep resonance dips with minimized ohmic losses. Electric-field distribution analysis demonstrates strong plasmon-induced field confinement near the sensing interface, with peak |E| intensities of approximately 2.4 × 10<sup>5</sup> V/m. Machine learning models predicted sensor behavior across different thicknesses and environmental conditions with coefficients of determination (R<sup>2</sup>) above 0.979 for layer thickness and 0.985 for refractive index. The resulting design offers high sensitivity refractive-index sensing, broad response range, and provide a foundation for future integration of biochemical functionalization toward selective biomarker detection.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1384 ","pages":"Article 344991"},"PeriodicalIF":6.0,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.aca.2025.344982
Diogo Gonçalves , Cláudia Ribeiro , João P.C. Tomé , Bruno Pedras , Zita Martins
Background
Fiber optic chemical sensors (FOCS) can be rapidly integrated in future instrument suites for in-situ extraterrestrial chemical characterizations. At low development and deployment costs, they can complement the analysis of more capable instruments. The contribution of FOCS can best be exemplified by the detection of 1,3-butadiene in Titan. This analyte is an unsaturated hydrocarbon of relevance for Titan's atmospheric chemistry and geology, but its detection poses challenges for current spectroscopy and mass spectrometry space instruments. Here, we report the design of the sensing core of a future space-mission-ready FOCS tailored to detect 1,3-butadiene in Titan's hydrocarbon environments.
Results
We report the discovery and characterization of the first fluorescent indicator for 1,3-butadiene. The off-on detection strategy is based on an inverse electron demand Diels-Alder click-reaction between the analyte and a tetrazine indicator, yielding emissive 1,4-dihydropyridazine derivatives, as confirmed by NMR. Excitation above 415 nm enables the selective detection of 1,3-butadiene against competing unsaturated hydrocarbons present in Titan. The sensor exhibited a limit of detection of 1.1 ppm (mol mol−1) and a linear response up to the expected saturation concentration in Titan's lakes. Furthermore, the fast and irreversible reaction between the tetrazine indicator and 1,3-butadiene provides rapid sensor responses that increase with temperature. Operating the sensor at high temperatures also mitigates competing photobleaching reactions. The immobilization of the indicator in polystyrene membranes maintained its detection capability for 1,3-butadiene dissolved in hexane, an apolar solvent analogous to Titan's hydrocarbon lakes.
Significance
The demonstration of the solid-state functionality of the indicator marks the last step towards its integration with space-qualified instrumentation. This proof-of-principle detection of 1,3-butadiene highlights the potential of fluorescence sensing for probing exotic planetary environments. Fiber optic architectures are ideal platforms for adapting fluorescence-based chemical sensing strategies to the in-situ characterization of extraterrestrial sites.
{"title":"Towards fiber optic chemical sensors for 1,3-butadiene detection in Titan's hydrocarbon lakes","authors":"Diogo Gonçalves , Cláudia Ribeiro , João P.C. Tomé , Bruno Pedras , Zita Martins","doi":"10.1016/j.aca.2025.344982","DOIUrl":"10.1016/j.aca.2025.344982","url":null,"abstract":"<div><h3>Background</h3><div>Fiber optic chemical sensors (FOCS) can be rapidly integrated in future instrument suites for <em>in-situ</em> extraterrestrial chemical characterizations. At low development and deployment costs, they can complement the analysis of more capable instruments. The contribution of FOCS can best be exemplified by the detection of 1,3-butadiene in Titan. This analyte is an unsaturated hydrocarbon of relevance for Titan's atmospheric chemistry and geology, but its detection poses challenges for current spectroscopy and mass spectrometry space instruments. Here, we report the design of the sensing core of a future space-mission-ready FOCS tailored to detect 1,3-butadiene in Titan's hydrocarbon environments.</div></div><div><h3>Results</h3><div>We report the discovery and characterization of the first fluorescent indicator for 1,3-butadiene. The off-on detection strategy is based on an inverse electron demand Diels-Alder click-reaction between the analyte and a tetrazine indicator, yielding emissive 1,4-dihydropyridazine derivatives, as confirmed by NMR. Excitation above 415 nm enables the selective detection of 1,3-butadiene against competing unsaturated hydrocarbons present in Titan. The sensor exhibited a limit of detection of 1.1 ppm (mol mol<sup>−1</sup>) and a linear response up to the expected saturation concentration in Titan's lakes. Furthermore, the fast and irreversible reaction between the tetrazine indicator and 1,3-butadiene provides rapid sensor responses that increase with temperature. Operating the sensor at high temperatures also mitigates competing photobleaching reactions. The immobilization of the indicator in polystyrene membranes maintained its detection capability for 1,3-butadiene dissolved in hexane, an apolar solvent analogous to Titan's hydrocarbon lakes.</div></div><div><h3>Significance</h3><div>The demonstration of the solid-state functionality of the indicator marks the last step towards its integration with space-qualified instrumentation. This proof-of-principle detection of 1,3-butadiene highlights the potential of fluorescence sensing for probing exotic planetary environments. Fiber optic architectures are ideal platforms for adapting fluorescence-based chemical sensing strategies to the <em>in-situ</em> characterization of extraterrestrial sites.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1384 ","pages":"Article 344982"},"PeriodicalIF":6.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.aca.2025.344985
Jiale Wang , Minghua Deng , Chuanquan Wang , Kunpeng Niu , Ning Wang , Jinhua Li , Binyun Xia , Liyun Ding , Huan Yang , Xiaohan Chen , Jiayi Zhu
Background
Efficient and rapid identification of trace amounts of microRNA-21 (miRNA-21), an oncogenic miRNA, is conducive to the early diagnosis of prostate cancer. Despite extensive research efforts, the development of biosensors capable of achieving clinically relevant sensitivity and limits of detection (LOD) remains challenging, primarily due to the ultralow physiological concentrations of cancer biomarkers in human biological systems. Beyond that, the suboptimal probe designs such as complex sensing structures and unstable sensing materials collectively lead to inadequate repeatability and stability for clinical application.
Results
Hence, in this work, a label-free and highly sensitive optical fiber Surface Plasmon Resonance (SPR) biosensor with ultralow LOD was developed for detecting miRNA-21, which was fabricated simply by coating a layer of Au film and gold nanoparticles (AuNPs) onto a multimode-single-mode-multimode (MSM) optical fiber, and then biofunctionalized with optimized single-stranded DNA (ssDNA) enabling the quantification of miRNA-21. Excitingly, the biosensors, which have a simple composition and demonstrated with excellent linearity, specificity and stability, were experimentally verified to reach an ultra-low LOD of 1.86 × 10–19 M that significantly lower than current detection method and high sensitivity of 3021.48 RIU/nm. And detection of trace miRNA-21 was enabled without RNA amplification. The sensor's capability to effectively differentiate prostate cancer patients from healthy controls was demonstrated by testing clinical serum samples and the sensor achieved higher detection accuracy compared to the commonly used clinical prostate-specific antigen (PSA) quantification.
Significance
The proposed sensing platform processes the merits of simple configuration as well as low cost and has potential to auxiliary early-stage diagnosis of various cancers by detecting associated biomarkers.
{"title":"Ultra-sensitive optical fiber SPR biosensor for assisted diagnosis of prostate cancer by label-free detection of miRNA-21","authors":"Jiale Wang , Minghua Deng , Chuanquan Wang , Kunpeng Niu , Ning Wang , Jinhua Li , Binyun Xia , Liyun Ding , Huan Yang , Xiaohan Chen , Jiayi Zhu","doi":"10.1016/j.aca.2025.344985","DOIUrl":"10.1016/j.aca.2025.344985","url":null,"abstract":"<div><h3>Background</h3><div>Efficient and rapid identification of trace amounts of microRNA-21 (miRNA-21), an oncogenic miRNA, is conducive to the early diagnosis of prostate cancer. Despite extensive research efforts, the development of biosensors capable of achieving clinically relevant sensitivity and limits of detection (LOD) remains challenging, primarily due to the ultralow physiological concentrations of cancer biomarkers in human biological systems. Beyond that, the suboptimal probe designs such as complex sensing structures and unstable sensing materials collectively lead to inadequate repeatability and stability for clinical application.</div></div><div><h3>Results</h3><div>Hence, in this work, a label-free and highly sensitive optical fiber Surface Plasmon Resonance (SPR) biosensor with ultralow LOD was developed for detecting miRNA-21, which was fabricated simply by coating a layer of Au film and gold nanoparticles (AuNPs) onto a multimode-single-mode-multimode (MSM) optical fiber, and then biofunctionalized with optimized single-stranded DNA (ssDNA) enabling the quantification of miRNA-21. Excitingly, the biosensors, which have a simple composition and demonstrated with excellent linearity, specificity and stability, were experimentally verified to reach an ultra-low LOD of 1.86 × 10<sup>–19</sup> M that significantly lower than current detection method and high sensitivity of 3021.48 RIU/nm. And detection of trace miRNA-21 was enabled without RNA amplification. The sensor's capability to effectively differentiate prostate cancer patients from healthy controls was demonstrated by testing clinical serum samples and the sensor achieved higher detection accuracy compared to the commonly used clinical prostate-specific antigen (PSA) quantification.</div></div><div><h3>Significance</h3><div>The proposed sensing platform processes the merits of simple configuration as well as low cost and has potential to auxiliary early-stage diagnosis of various cancers by detecting associated biomarkers.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1384 ","pages":"Article 344985"},"PeriodicalIF":6.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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