Cisplatin (DDP), as a broad-spectrum anticancer drug, requires dynamic monitoring of its blood concentration and intervention in its dosage administration to balance efficacy and safety due to significant individual differences in its metabolism, side effects, and resistance in different patients. However, rapid and robust methods for monitoring and quantifying DDP in complex biological fluids are still lacking. This work presents an electrochemical aptamer-based (E-AB) sensor for rapid measurement of DDP concentration in blood. In which capture probe aptamers were designed constructed by visualizing and analyzing their binding pockets, followed by molecular docking and circular dichroism to screen the aptamer Apt25, which has a small binding energy and a large conformational change, for use in the construction of the sensor. In the presence of DDP, the aptamer undergoes a conformational change at the electrode interface, altering the electron transfer rate of the electroactive label to detect DDP concentration variations. After systematically using electrochemical techniques to optimize the sensor testing conditions, the sensor can directly analyze and detect DDP in urine and blood with a measurement range of 0.001-2 mM and a detection limit of 1 mu M, which satisfies the needs of clinical testing. The spiked recoveries in different biological samples were 80.8-110% and 79-115.2%, respectively. In addition, the sensor has sufficient selectivity and stability, which is expected to enable real-time monitoring of DDP concentration for dosage adjustment and improvement of drug bioavailability at the clinical site.

2,2 '-methylenebis (4-chlorophenol) (dichlorophen, Dcp) is a potently toxic and persistent environmental contaminant that is difficult to detect at low concentrations. This study presents a novel electrochemical sensor using erbium-gadolinium bimetallic organic framework-derived porous carbon (Er2O3-Gd2O3@C) for efficient Dcp detection in environmental water. The Er-Gd-MOF precursor was synthesized hydrothermally and subsequently carbonized at high temperature to obtain Er2O3-Gd2O3@C. Material characterization with scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) method and electrochemical methods confirmed the successful preparation of Er2O3-Gd2O3@C cubes. Endowed with a large electrochemically active surface area and abundant catalytic sites, the material thus exhibited excellent detection performance. The prepared sensor showed outstanding electrocatalytic activity toward Dcp with a wide linear range of 10 nM to 20 mu M and a low detection limit of 7.2 nM. It also exhibited good repeatability, selectivity and stability. Importantly, the sensor was successfully implemented for real water samples, achieving recoveries between 92.1% and 103.1%. This work provides an electrochemical analytical platform with promising potential for monitoring environmental pollutants.

Modulation of the dynamic instability of electrochemical systems has been shown to create Turing patterns within electrode feature structures. This is crucial for the formation of bottom-up filled interconnected metal layers in chip advanced packaging processes, represented by through glass vias (TGV). However, the currently available additives are very limited and struggle to provide stable kinetic bifurcation regions in the galvanostatic mode favored for industrial applications. In this paper, the potential of an azole small molecule for generating Turing patterns was identified. And through the subsequent introduction of another assisted polymer molecules, the kinetic bifurcation capability of the Turing-type additive inside and outside the glass recessed features (25:225 mu m, V-shaped blind vias) was optimized. The mechanism of electrochemical Turing patterns generation by the interaction of two additives was investigated using in-situ electrochemical-surface-enhanced Raman spectroscopy and electron backscatter diffraction imaging. Furthermore, the spatial distribution and time-dependent behavior of the additives and metal ions at the electrode interface were reorganized with the reverse pulse electrochemical technique, ultimately achieving uniform, defect-free bottom-up copper deposition of TGV. This strategy demonstrates the feasibility of utilizing Turing instability to generate regular structures, expanding the application of electrochemical interfacial nonlinear phenomena in the field of microfabrication.

Ribonuclease H (RNase H) is widely involved in key biological processes such as DNA replication, RNA transcription, and DNA repair, and it is emerging as an important therapeutic target for various diseases. In this study, a plasmonic gold nanocube-enhanced surface-enhanced Raman scattering (SERS) biosensor was developed for highly sensitive detection of RNase H activity by simultaneously integrating instant dehydration in butanol (INDEBT) for SERS tags preparation, copper-free click chemistry for SERS tag conjugation and exonuclease III (Exo III)-assisted target cyclic amplification. The INDEBT method enabled a simpler and highly efficient preparation of SERS tags. Additionally, click chemistry for SERS tags conjugation to the bio-sensing platform circumvented nanoparticle aggregation risk caused by high salt buffer solution necessary for DNA hybridization method in the previous studies. While the sharp geometric features of AuNCs for effective SERS enhancement and Exo III-assisted cyclic amplification stragety significantly enhanced the detection sensitivity. Under optimized experimental conditions, the proposed method exhibited high sensitivity and good selectivity, achieving a limit of detection (LOD) as 3.89 × 10-7 U μL-1, which was lower than most reported values in the literature. Furthermore, this method was successfully applied to the detection of RNase H activity in real cellular extracts.

The rapid, simple, and low-cost detection of potent analgesic drugs like morphine is essential for the precise clinical use of these drugs. However, existing detection methods typically require trained operators, expensive experimental instruments, and complicated sample pretreatment procedures. This greatly limits the potential application of these drugs. An electrochemical sensor that utilizes conformational shifts in aptamers to swiftly and selectively detect morphine in human body fluids was designed. The aptamer’s structural energy and its energy change after binding morphine were used as the basis for determining whether the aptamer experienced a structural transition after morphine binding. Analysis and validation of the results were performed using circular dichroism (CD) spectroscopy. Following screening, the aptamer chains were attached to a gold electrode surface via self-assembled Au‒S bonds, resulting in the formation of an electrochemical aptamer sensor. The experimental results showed that the developed sensor exhibited excellent reproducibility and stability. It was responsive to 10 nmol/L morphine and could be used to accurately quantify morphine at concentrations of 100 nmol/L and higher. Therefore, this study provides a new approach for the rapid and accurate detection of morphine in human body fluids.

Transfusion-related acute lung injury (TRALI) remains a serious complication of transfusion, and blood component–derived exosomes have been proposed as candidate contributors to transfusion-related inflammatory dysregulation. Rapid and practical methods to assess exosome burden in stored red blood cell (RBC) units remain limited. Here, we developed a CD63 electrochemical aptamer-based (E-AB) sensor as a preliminary analytical platform to rapidly detect exosome-associated signals and investigated whether stored red-blood-cell–derived exosomes (EXs-RBC) contribute to mast-cell–associated inflammatory lung injury in TRALI-relevant models. Using the CD63 E-AB sensor, we assessed EXs-RBC signals in stored RBC units, isolated EXs-RBC for HMC-1 cell stimulation and mouse experiments, and evaluated their inflammatory effects. The CD63 E-AB readout decreased in a concentration-dependent manner with increasing exosome levels. EXs-RBC dose-dependently amplified inflammatory responses, and these effects were attenuated by pharmacologic mast-cell inhibition or mast-cell deficiency. In antibody-independent TRALI-relevant inflammatory lung injury models and a supportive antibody-mediated TRALI-like model, EXs-RBC exacerbated lung injury and were associated with activation of the mast-cell toll-like receptor 3 (TLR3)–mitogen-activated protein kinase (MAPK) signaling. Collectively, these findings support the feasibility of using a CD63 E-AB sensor to assess exosome burden in stored RBC units and provide experimental evidence that EXs-RBC can amplify mast-cell-associated inflammatory lung injury in TRALI-relevant models, supporting further investigation of EXs-RBC burden as a candidate donor-side metric in transfusion safety research.

Electrochemiluminescence (ECL) has achieved significant commercial success over the past few decades across various fields, particularly in the healthcare industry. The measurement scheme oftentimes involves target recognition elements (e.g. catching antibodies) labeled with a suitable ECL luminophore (e.g. tris(2,2'-bipyridine)ruthenium(II))). While this approach realizes the ultrasensitive detection of various biomarkers, it is somewhat complicated strategy for certain targets such as enzymes. In this study, β-glucuronidase (B-GLU), a promising biomarker and a common water/foodstuff safety indicator, was quantified by measuring the ECL signal of fluorescent product generated from non-fluorescent substrate by the B-GLU enzyme. To this end, hot electron-induced ECL of three luminophores (fluorescein, 4-methylumbelliferyl and resorufin) that are used as building blocks to synthesize various commercially available non-fluorescent substrates was compared for the first time. To increase the appeal and practicality of this approach, the common multi-well assay format was adapted to the present type ECL by carrying out the ECL reactions at single carbon black/polystyrene electrode. In this electrochemical setup, multiple cells were fabricated on the surface of a poorly conducting substrate by attaching Teflon tape with multiple holes to the substrates surface. Sample throughput time decreases considerable as target, blank and sample signals can be simultaneously obtained from the electrochemical cells when voltage is applied across the single electrode. The detection limit for B-GLU after 2 h of incubation was 0.07 U L-1 when 4-methylumbelliferyl-β-D-glucuronide was used as the fluorogenic substrate and Br- was used as the co-reactant. B-GLU recovery rates from diluted saliva with the present ECL approach were adequate (93-103 %) and similar to those obtained with the fluorescence technique.

Bisphenol A (BPA) is widely employed in the production of plastic bottles and food packaging. However, excessive BPA poses significant environmental and biological risks, highlighting the importance of sensitive detection methods. Herein, a novel ternary composite material was prepared using aminopropyl-functionalized magnesium phyllosilicate (AMP), metal-organic frameworks (MOFs) of zeolitic imidazolate framework-8 (ZIF-8) and multi-walled carbon nanotubes (MWCNTs) through a two-step synthesis approach. This material was applied to the sensitive electrochemical detection of BPA by directly oxidizing the target molecule at the modified electrode. The utilization of AMP, which suffers from poor aqueous stability, was realized by combining it with ZIF-8. The introduction of MWCNTs improved the conductivity of ZIF-8@AMP, thereby enhancing the detection performance of the ZIF-8@AMP/MWCNTs modified electrode. Given the high specific surface area, strong electron conductivity and excellent stability of ZIF-8@AMP/MWCNTs composites, BPA was detected with the linear range (0.04-46.9 mu M) and the low limit of detection (LOD, 3.2 nM). Moreover, the sensor can detect BPA sensitively in tap water, lake water and milk with recoveries of 91.9-104.8 %. In addition, this sensor also exhibits good reproducibility, stability and selectivity, firstly providing a new method for the detection of BPA.

Acute myocardial infarction (AMI) is one of the top contributors to global disease mortality. AMI biomarkers, such as cardiac troponin I (cTnI), are often detected with enzyme-linked immunosorbent assay (ELISA) that suffers from several well-known drawbacks such as poor stability and slow and cumbersome operation. Therefore, it is necessary to develop a new analytical technique that can rapidly analyse and detect cTnI for early screening of AMI. In this work, a nanoporous electrochemical aptamer-based (E-AB) sensor for rapid and sensitivite detect of cTnI was designed. Firstly, the aptamer was truncated, and then molecular docking simulation and circular dichroism (CD) were used to screen for aptamers with significant conformational changes when binding to the target, in order to enhance the sensitivity of E-AB sensors. Subsequently, nanoporous electrodes with active area 20 times higher than that of smooth electrodes were fabricated by electrochemical alloying/dealloying, which enabled E-AB sensors to obtain higher signal-to-noise ratios, providing favorable assurance for the detection results. Under optimal conditions, E-AB sensors could specifically detect cTnI in serum and blood with a detection limit of 1 pg/mL. At the same time, the sensor and enzyme-linked immunoassay (ELISA) had identical detection results when measuring target levels from real clinical samples. Furthermore, the sensor exhibited good reproducibility, stability, providing a simple and low-cost method for detecting cTnI, which is expected to help early AMI patients obtain accurate diagnosis.

2,2-methylenebis(4-chlorophenol) also known as dichlorophen (Dcp) is a highly toxic environmental pollutant that persists at low concentrations and is notoriously resistant to degradation. Consequently, it is highly important to develop a simple and rapid detection assay for Dcp. This study presents a one-pot synthesis of novel nanocomposites based on a lanthanum-based metal-organic framework (La-MOF), water-soluble R-cyclodextrin (R-CD) and fullerene (C60). La-MOF@C60/R-CD nanocomposite was integrated into a glassy carbon electrode (GCE) to create a new electrochemical sensor for Dcp detection. La-MOFs have a large specific surface area with copious electrocatalytic active sites, but the low conductivity of La-MOF limits its electrochemical performance. To overcome this, the conductivity was improved by the incorporation of C60 into La-MOF. Furthermore, the host-guest interaction facilitated by R-CD endows the La-MOF@C60/R-CD-modified electrode with superior electrocatalytic activity towards Dcp oxidation. The resulting sensor offers sensitive Dcp detection, with a linear response range from 30 nM to 25 mu M and a limit of detection (LOD) of 11.6 nM. It also exhibits excellent signal reproducibility, sensor stability, and selectivity towards Dcp. Furthermore, the strategy was effectively applied to the determination of Dcp in real water samples, achieving satisfactory recoveries between 93.3 % and 102.6 %.

The metabolic differences between patients with the anticancer drug daunorubicin (DRN) pose difficulties in providing clinical delivery strategies for different patients. Therefore, it is urgent to develop a pharmacokinetic platform that can real-time monitor drug levels in vivo to achieve precise drug delivery and reduce drug side effects. To this end, an electrochemical aptamer-based (E-AB) sensor was designed to realize real-time and continuous monitoring of DRN levels in vivo and obtain DRN pharmacokinetics of different individuals for the first. Specifically, the binding free energy of the aptamer to the target was calculated by molecular docking simulations. Using nanoporous gold working electrodes with immobilized aptamers as E-AB sensors, which monitored DRN in the blood of different rat models continuously for many hours with nanomolar precision and second resolution, and hundreds of DRN concentration values were obtained, based on which important pharmacokinetic parameters were simulated and computed, including half-life of drug DRN distribution and elimination, and peak concentration in blood. These parameters help to determine the metabolism of drug DRN in different patients and adjust the administered dose in time to achieve precise treatment. Therefore, this E-AB platform may provide a valuable new tool for clinicians to monitor pharmacokinetics in different patients.

Background: The fabrication of sensors capable of achieving rapid, sensitive, and highly selective detection of target molecules in complex fluids is key to realizing their real-world applications. For example, there is an urgent need in drugged driving roadside screening scenarios to develop a method that can be used for rapid drug detection and that avoids interference from the matrix in the sample. How to minimize the interference of complex matrices in biofluids at the electrode interface is the key to improve the sensitivity of the sensor. Results: This work develops a facile and green method to prepare rough electrodes with a porous structure for constructing electrochemical aptamer-based (EAB) sensors for rapid, sensitive and accurate detection of Delta(9 )tetrahydrocannabinol (THC) in biofluids. The electroactive area of the rough electrode was 21 times of smooth electrode. And the antifouling performance of the rough electrode was much better than that of smooth electrode. Based on the unique advantages of the rough electrode, the developed EAB sensor achieves rapid nanomolar detection of THC in undiluted serum, undiluted urine and 50 % saliva with the detection limit of 5.0 nM, 10 nM and 10 nM, respectively. Moreover, our method possesses good reproducibility, accuracy and specificity. Significance: The porous structure can effectively reduce the non-specific adsorption and enhance the stability of the signal, while the larger active area can modify more aptamers, thus improving the sensitivity. The detection limits of the EAB sensor were lower than the cutoff concentration of THC in drugged driving and the measuring process was completed within 60 s after target addition, which makes the present sensors capable for real-world applications.

The flap endonuclease 1 (FEN1) plays a key role in DNA replication and repair, its aberrant expression is associated with tumor development, so it has been recognized as a promising biomarker for a variety of cancers. Here, a novel "turn on" mode gold nanocube-enhanced surface-enhanced Raman scattering (SERS) biosensor was constructed by combining a heated Au electrode (HAuE), exonuclease III (Exo III)-assisted cycle amplification, and gold nanocube (AuNC)-based SERS enhancement to achieve highly sensitive detection of FEN1 activity. The SERS tag was prepared using the Raman reporter modified on the AuNC surface, and the high electromagnetic field provided by the sharp geometric feature of AuNC greatly enhanced the SERS signal. At the same time, HAuE was used to increase the electrode surface temperature and enhance the FEN1 activity, leading to more trigger DNA being cleaved, which was used to initiate the Exo III-assisted cycle amplification. Taking all these advantages, the proposed method possessed high sensitivity and good selectivity, with a low limit of detection (LOD) of 3.19 × 10-7 U μL-1. In addition, this method was successfully applied to detect FEN1 activity in real cellular extracts.

Cocaine is one of the most abused illicit drugs, and its abuse damages the central nervous system and can even lead directly to death. Therefore, the development of simple, rapid and highly sensitive detection methods is crucial for the prevention and control of drug abuse, traffic accidents and crime. In this work, an electrochemical aptamer-based (EAB) sensor based on the low-temperature enhancement effect was developed for the direct determination of cocaine in bio-samples. The signal gain of the sensor at 10 °C was greatly improved compared to room temperature, owing to the improved affinity between the aptamer and the target. Additionally, the electroactive area of the gold electrode used to fabricate the EAB sensor was increased 20 times by a simple electrochemical roughening method. The porous electrode possesses more efficient electron transfer and better antifouling properties after roughening. These improvements enabled the sensor to achieve rapid detection of cocaine in complex bio-samples. The low detection limits (LOD) of cocaine in undiluted urine, 50

Hydrated electrons were generated at boron doped diamond electrodes in fully aqueous solutions during cathodic pulse polarization and utilized for the electrochemiluminescence (ECL) determination of alkaline phosphatase (ALP) by adapting one of the most common fluorescent methods. In this approach, highly fluorescent 4-methylumbelliferyl (MU) is enzymatically generated from non-fluorescent 4-methylumbelliferyl phosphate (MUP) substrate and chemically excited in the presence of oxidizing radicals and reducing hydrated electrons. A novel time-resolved internal standard strategy is presented to counter matrix effects to certain degree and to lower signal variation among concurrent measurements. In this unique approach, the cathodic ECL signals of MU and Tb(III)-chelate were separated on the basis of their exceptionally different excited state lifetimes. This enabled more precise determination of ALP by simply measuring the ratio of ECL emissions during and after cathodic excitation pulse with simple two-electrode, single photomultiplier tube setup. The ratiometric ECL signals in the absence and presence of 1.0 % serum (v/v) were interchangeable whereas ratiometric signal recovery in the presence of 10.0 % serum was similar to 85 %.

Real-time, high-frequency measurements of pharmaceuticals, metabolites, exogenous antigens, and other biomolecules in biological samples can provide critical information for health management and clinical diagnosis. Electrochemical aptamer-based (EAB) sensor is a promising analytical technique capable of achieving these goals. However, the issues of insufficient sensitivity, frequent calibration and lack of adapted portable electrochemical device limit its practical application in immediate detection. In response we have fabricated an on-chip-integrated, cold-hot Janus EAB (J-EAB) sensor based on the thermoelectric coolers (TECs). Attributed to the Peltier effect, the enhanced/suppressed current response can be generated simultaneously on cold/hot sides of the J-EAB sensor. The ratio of the current responses on the cold and hot sides was used as the detection signal, enabling rapid on-site, calibration-free determination of small molecules (procaine) as well as macromolecules (SARS-CoV-2 spike protein) in single step, with detection limits of 1 μM and 10 nM, respectively. We have further demonstrated that the J-EAB sensor is effective in improving the ease and usability of the actual detection process, and is expected to provide a universal, low-cost, fast and easy potential analytical tool for other clinically important biomarkers, drugs or pharmaceutical small molecules.

Electrodeposition plays an indispensable role in microelectronic process. Copper pillar bumps (CPBs) have received widespread attention in advanced packaging. Clarifying the effects of additives is essential to obtain the uniform, leveling and void-free filled layer. However, the observation platform to achieve efficient screening of various additive combinations is absent. Herein, taking advantage of the highly transparent characteristic of microcavity electrode (MCE) as well as its similarity to the practical working conditions of CPBs, the convection-dependence of the copper filling layer (500-25 mu m, aspect ratio similar to 1) was observed. The leveling effect of the additives with the modulating flow and electric fields was visualized. In-situ observations and electrochemical evidences support that accelerated growth of the downstream front can only be observed when all three organic additives are present simultaneously. Although the introduction of convection can accelerate the renewal of additives on the surface of the filled layer, the antagonistic effect of Janus Green B (JGB) on sodium 3,3 '-disulfanediylbis(propane-1-sulfonate) (SPS) is weakened due to the rapid decomposition of JGB within the microcavity, thereby amplifying the accumulation effect of SPS downstream in the microcavity. Consequently, the competitiveness of SPS against polyethylene glycol (PEG) on that side (depolarization) is enhanced, and a non-uniform distribution of the filled layer is established. As the protrusion approaches the mouth of the microcavity, the sufficient supply of JGB reverses the height bias. This work demonstrates the value of this in-situ observation platform in parameters optimizing and mechanisms studying.

Imatinib (Ima), as a commonly used anticancer drug for the clinical treatment of leukemia and gastrointestinal mesenchymal stromal tumour, requires timely monitoring of patients' blood concentration to ensure efficacy while reducing complications and achieving precision medicine due to its narrow therapeutic window (1-5 μM) and the varying sensitivity and resistance of different patients to Ima. However, traditional assays are slow and cumbersome, so improved and innovative platforms for monitoring Ima in the clinic are necessary. In this work, a nanoporous electrochemical aptamer-based (E-AB) sensor was designed for the detection of Ima and imatinib mesylate (Ima-Mes) in blood. Apt-37, a high-affinity and conformationally variable aptamer, was screened by molecular docking simulation calculations and circular dichroism (CD) for the construction of the E-AB sensor. The sensor detected Ima and Ima-Mes in the range of 0.1 μM-1 mM, and the recoveries in spiked blood samples were in the range of 70.7 %-104.6 % and 74.8 %-113.9 %, respectively. The precision and accuracy of the E-AB sensor for measuring Ima-Mes concentration in blood was similar to the standard LC-MS method. These results demonstrate that the developed E-AB sensor is an effective tool for rapid monitoring of Ima and Ima-Mes in blood.