A mesothelin microsensor based on an embedded thionine electronic medium within an imprinted polymer on an acupuncture needle electrode.

An electrochemical microsensor for mesothelin (MSLN) based on an acupuncture needle (AN) was constructed in this work. To prepare the microsensor, MSLN was self-assembled on 4-mercaptophenylboronic acid (4-MPBA) by an interaction force between the external cis-diol and phenylboronic acid. This was followed by the gradual electropolymerization of thionine (TH) and eriochrome black T (EBT) around the anchored protein. The thickness of the surface imprinted layers influenced the sensing performance and needed to be smaller than the height of the anchored protein. The polymerized EBT was not electrically active, but the polymerized TH provided a significant electrochemical signal. Therefore, electron transfer smoothly proceeded through the eluted nanocavities. The imprinted nanocavities were highly selective toward MSLN, and the rebinding of insulating proteins reduced the electrochemical signal of the embedded pTH. The functionalized interface was characterized by SEM and electrochemical methods, and the preparation conditions were studied. After optimization, the sensor showed a linear response in the range of 0.1 to 1000 ng mL-1 with a detection limit of 10 pg mL-1, indicating good performance compared with other reported methods. This microsensor also showed high sensitivity and stability, which can be attributed to the fine complementation of the imprinted organic nanocavities. The sensitivity of this sensor was related to the nanocavities used for electron transport around the AuNPs. In the future, microsensors that can directly provide electrochemical signals are expected to play important roles especially on AN matrices.

A chiral sensing platform based on a multi-substituted ferrocene-cuprous ion complex for the discrimination of electroactive amino acid isomers.

An electrochemical chiral sensing platform based on a multi-substituted ferrocene-cuprous ion (Cu+) complex is constructed for the discrimination of electroactive amino acid (AA) isomers. Due to the opposite configurations of the AA isomers, the developed multi-substituted ferrocene-Cu+ can preferably combine with a right-handed AA (D-AA) isomer to form the ternary complex of multi-substituted ferrocene-Cu+-D-AA through π-π interactions, resulting in higher peak currents of D-AA. Therefore, the isomers of electroactive AA can be successfully discriminated. Among the tested electroactive AA isomers, the chiral sensing platform exhibits higher discrimination capability toward the isomers of tryptophan (Trp) than that of tyrosine (Tyr) and cysteine (Cys), which might be ascribed to the stronger π-π interactions between the benzene ring of the multi-substituted ferrocene and the indole ring of the Trp isomers.

An electrochemical chlorpromazine sensor based on a gold-copper bimetallic synergetic molecularly imprinted interface on an acupuncture needle electrode.

Chlorpromazine (CPZ) is a medicine for nervous system disorders. Measuring CPZ in vivo can assist doctors in evaluating patients' blood drug concentration and monitoring drug metabolism. Therefore, an accurate in vivo detection of CPZ is crucial. In recent years, the acupuncture needle, traditionally used in Chinese medicine, has emerged as a potential electrode in the field of electrochemistry, with promising applications for in vivo detection. In this study, Au/Cu nanoparticles were electrodeposited onto an acupuncture needle electrode (ANE) to improve electrical conductivity and provide an electro-catalytic surface. Subsequently, 3-aminophenylboronic acid and CPZ were attracted to each other through intermolecular forces; at the same time, the interaction force of Au-S between CPZ and the AuNPs made the polymer layer grow around the CPZ molecules on the modified electrode surface. The imprinted nanocavities showed highly selective and sensitive detection performance for CPZ after elution. Inside the recognizable site and microenvironment of the cavities, the captured CPZ molecule provided a suitable configuration for the fluent electron transfer of the electroactive group within a short range from the Au/Cu bimetal. Under ideal conditions, the MIP/Au/Cu/ANE exhibited two good linear ranges of 0.1-100 µM and 100-1000 µM with a detection limit of 0.07 µM. Moreover, the sensors showed great selectivity, good stability and excellent repeatability, making them suitable for CPZ detection in human serum. This provides a novel idea for real-time and in vivo CPZ detection.

An electrochemical chiral sensor based on competitive host-guest interaction for the discrimination of electroinactive amino acids.

A novel electrochemical chiral sensor has been designed based on the principle of competitive host-guest interaction and utilized for the discrimination of electroinactive proline (Pro) isomers. Electroactive methylene blue (MB) was used as the signal probe, which was combined with multi-walled carbon nanotubes (MWCNTs)-decorated ß-cyclodextrin (ß-CD), via host-guest interaction, where the oxidation peak currents of MB decreased after isomers of Pro were combined with the MWCNTs-ß-CD via a competitive host-guest interaction. Due to the steric configuration of L-Pro matching the cavity of ß-CD, more L-Pro than D-Pro was combined with MWCNTs-ß-CD, resulting in a more pronounced decrease of MB peak currents. Therefore, the isomers of Pro could be discriminated. Besides Pro, the isomers of electroinactive histidine (His) could also be discriminated with the chiral sensor. In addition, the contents of L-Pro in non-racemic mixtures could be detected with the developed chiral sensor.

A surface protein-imprinted biosensor based on boronate affinity for the detection of anti-human immunoglobulin G.

A surface protein-imprinted biosensor was constructed on a screen-printed carbon electrode (SPCE) for the detection of anti-human immunoglobulin G (anti-IgG). The SPCE was successively decorated with aminated graphene (NH2-G) and gold nanobipyramids (AuNBs) for signal amplification. Then 4-mercaptophenylboric acid (4-MPBA) was covalently anchored to the surface of AuNBs for capturing anti-IgG template through boronate affinity binding. The decorated SPCE was then deposited with an imprinting layer generated by the electropolymerization of pyrrole. After removal of the anti-IgG template by the dissociation of the boronate ester in an acidic solution, three-dimensional (3D) cavities complementary to the anti-IgG template were formed in the imprinting layer of polypyrrole (PPy). The molecularly imprinted polymers (MIP)-based biosensor was used for the detection of anti-IgG, exhibiting a wide linear range from 0.05 to 100 ng mL-1 and a low limit of detection of 0.017 ng mL-1 (S/N = 3). In addition, the MIP-based anti-IgG biosensor also shows high selectivity, reproducibility and stability. Finally, the practicability of the fabricated anti-IgG biosensor was demonstrated by accurate determination of anti-IgG in serum sample.

Ultrasensitive Electrochemical Impedance Chiral Discrimination and Sensing of Tryptophan Isomers Based on Core-Shell-Structured Au-Ag Nanoparticles.

Au-Ag nanoparticles (Au-Ag NPs) with a core-shell structure are prepared and used for ultrasensitive electrochemical impedance (EI) discrimination of the isomers of tryptophan (Trp). As revealed by circular dichroism, rotary polarization caused by the Au-Ag NPs is consistent with D-Trp but opposite to L-Trp, and thus, the Au-Ag NPs can selectively combine with D-Trp through preferential interactions. Compared with Au-Ag NPs, the composites of D-Trp and Au-Ag NPs (Au-Ag NPs/D-Trp) display significantly increased charge transfer resistance (Rct); differently, the Rct of Au-Ag NPs/L-Trp remains almost unchanged because the Au-Ag NPs exhibit poor affinity toward L-Trp. Therefore, ultrasensitive EI enantiodiscrimination of the isomers of Trp is realized even at an extremely low concentration of the Trp isomers (0.1 nM). In addition, it is successfully applied in the ultrasensitive determination of D-Trp at a low concentration level (0.1 nM∼10 µM).

Electrochemiluminescent chiral discrimination with chiral Ag2S quantum dots/few-layer carbon nitride nanosheets.

Well-dispersed chiral Ag2S quantum dots (Ag2S QDs) were facilely synthesized by using N-acetyl-L-cysteine (NALC) as the chiral ligand and loaded onto nanosheets of two-dimensional (2D) few-layer carbon nitride (C3N4). The resultant nanocomposite (Ag2S QDs/few-layer C3N4) shows enhanced electrochemiluminescence (ECL) while maintaining the chirality of Ag2S QDs, which can be used for the chiral discrimination of the enantiomers of tyrosine (Tyr). Due to the higher affinity of chiral Ag2S QDs toward L-Tyr than toward its enantiomer, the ECL intensity of Ag2S QDs/few-layer C3N4 is significantly decreased after its incubation with L-Tyr, and thus the Tyr enantiomers can be discriminated. The developed ECL chiral sensor exhibits high stability and reproducibility. The universality of the ECL chiral sensor for the discrimination of other chiral amino acids is also studied, and the results indicate that it can work only in the case of chiral aromatic amino acids.

Chiral Enantioselective Assemblies Induced from Achiral Porphyrin by l- and d-Lysine.

π-Conjugated porphyrins have aroused particular attention for nanofabrication and biomimics; however, little attention has been paid to porphyrins-based chiral analysis owing to the achiral feature of porphyrins. Here, we demonstrated a chiral self-assembly of achiral porphyrin induced by l- and d-lysine (l- and d-Lys), and the resultant porphyrin self-assembly exhibited alterable morphologies depending on the inducer used (l- or d-Lys). The supramolecular chirality of the self-assembly was characterized by circular dichroism (CD) spectra, confirming successful transfer of molecular chirality from l- and d-Lys to the self-assembly. The enantioselective property of the chiral self-assembly was also investigated by using tryptophan (Trp) isomers as the model, and the results indicated that the developed chiral self-assembly showed significantly higher affinity toward l-Trp than d-Trp. Also in this work, the l-/d-Lys-induced chiral self-assembly of porphyrin and the supramolecular interaction between the self-assembly and l-/d-Trp were also studied by density functional theory (DFT).

G-Quadruplex DNA with an Apurinic Site as a Soft Molecularly Imprinted Sensing Platform.

Molecularly imprinted polymers (MIPs) provide versatile sensor platforms to recognize targets by shape complementarity. However, the rigid structure of the classic MIPs compromises the signal transduction with necessary polymer and target modifications. Herein, we tried to use a flexible DNA that has a perfectly structured folding as the soft molecularly imprinted polymer (SMIP) for a straightforward sensor. As a proof of concept, the guanosine SMIP recognition was achieved by removal of a guanosine from a G-quadruplex-forming sequence (G4). The G4 folding structure with such an apurinic site (AP site) provides a well-defined MIP binding accommodation for guanosine according to the shape complementarity. The guanosine binding at the AP site subsequently leads to a conformation change suitable for remote readout using a G4-specific fluorescent ligand. The G4 sequence and AP site position were optimized for this SMIP behavior. Due to the G4 compact structure and the remaining hydrogen bonding pattern, nucleosides other than guanosine and negatively charged nucleotides exhibit no binding with the AP site, suggesting a high selectivity in the SMIP recognition. The proposed rationale was then convinced by the alkaline phosphatase-catalyzed GMP hydrolysis. Our work will inspire more interest in exploring nucleic acids as the SMIP frameworks due to their variant conformations and well-established molecular engineering.

Adaptively Recognizing Parallel-Stranded Duplex Structure for Fluorescent DNA Polarity Analysis.

Besides the canonical Watson-Crick (WC) linked antiparallel-stranded duplex (aps-DNA), DNA is also able to form bioactive parallel-stranded duplex (ps-DNA) with the two involving strands adopting the equal 5'-3' polarity. Discriminating ps-DNA from aps-DNA with an ideal selectivity is more challenging because of their comparable duplex topologies. Herein, we designed a unique probe of HPIN to fluorescently recognize ps-DNA but to keep an almost nonfluorescent response in binding with aps-DNA. The success of the Hoogsteen hydrogen bonding pattern in lighting up the HPIN fluorescence over the reverse Watson-Crick (rWC) one suggests the critical role of HPIN in structurally adaptive recognition to the strand polarity-determined base-pairing peculiarity. The turn-on fluorescence should result from restriction of the HPIN cis/trans isomerization upon the adaptive Hoogsteen base pair binding. Such high performance in recognizing ps-DNA against aps-DNA demonstrates the promising applications of HPIN in developing unique DNA polarity-based sensors.

A photothermal effect-based chiral sensor for chiral discrimination and sensitive detection.

Chiral analysis with simple devices is of great importance for analytical chemistry. Based on the photothermal (PT) effect, a simple chiral sensor with a portable laser device as the light source and a thermometer as the detection tool was developed for the chiral recognition of tryptophan (Trp) isomers and the sensitive sensing of one isomer (L-Trp). Gold nanorods (GNRs), which have outstanding photo-thermal conversion ability due to their localized surface plasma resonance (LSPR) effect, are used as PT reagents, and biomacromolecules bovine serum albumin (BSA) are used as natural chiral sources, and thus, GNRs@BSA was obtained through Au-S bonds. The resultant GNRs@BSA displays higher affinity toward L-Trp than D-Trp owing to the inherent chirality of BSA. Under the irradiation of near-infrared (NIR) light, the temperature of GNRs@BSA//L-Trp is greatly lower than that of GNRs@BSA//D-Trp due to its greatly decreased thermal conductivity, and thus chiral discrimination of Trp isomers can be achieved. In addition, the developed PT effect-based chiral sensor can be used for sensitive detection of L-Trp, and the linear range and limit of detection (LOD) are 1 µM-10 mM and 0.43 µM, respectively.

Visual and electrochemical chiral discrimination of tryptophan isomers with shikimic acid chiral ionic liquids-copper ions complex.

Efficient discrimination of amino acids (AAs) isomers is of significant importance for life science and analytical chemistry. Here, a dual-mode chiral discrimination strategy is proposed for visual and electrochemical chiral discrimination of tryptophan (Trp) isomers. Shikimic acid chiral ionic liquids (SCIL) is coordinated with copper ions (Cu2+), and the obtained SCIL-Cu2+ can form ternary complexes with the Trp isomers. Owing to the inherent chirality of SCIL and the reverse homochirality of L-Trp and D-Trp, the ternary complex of SCIL-Cu-D-Trp has higher stability than SCIL-Cu-L-Trp, as revealed by the calculated stability constants (K) and changes in Gibbs free energy (ΔG). The difference in the stability can be utilized for the chiral discrimination of L-Trp and D-Trp, resulting in discernible differences in colors and the electrochemical signals of the Trp isomers. Besides Trp, the isomers of phenylalanine (Phe) can also be discriminated by the proposed dual-mode chiral discrimination strategy with the SCIL-Cu2+ complex.

Carboxymethyl potato starch hydrogels encapsulated cyclodextrin metal-organic frameworks for enantioselective loading of S-naproxen and its programmed release.

A natural polysaccharide-based vehicle is facilely prepared for enantioselective loading of S-naproxen (S-NPX) and its programmed release. Cyclodextrin metal-organic frameworks (CD-MOF) are synthesized through the coordination of K+ with γ-cyclodextrin (γ-CD). Compared with R-NPX, the CD-MOF preferably combines with S-NPX, which can be confirmed by the thermodynamic calculations. The S-NPX loaded CD-MOF (CD-MOF-S-NPX) is grafted with disulfide bond (-S-S-) to improve its hydrophobicity, and the loaded S-NPX is further encapsulated in the chiral cavity of γ-CD by carboxymethyl potato starch (CPS) hydrogels. The intermolecular hydrogen bonding of the CPS hydrogels is prone to be destroyed in mildly basic media (∼pH 8.0), resulting in the swelling of the hydrogels; the -S-S- linkage in the vehicle can be cleaved in the presence of glutathione (GSH), leading to the collapse of the CD-MOF. Therefore, the programmed release of S-NPX can be achieved. Also in this work, the release kinetics is investigated, and the results indicate that the release of S-NPX is controlled by the Higuchi model.

A sequential delivery system based on MoS2 nanoflower doped chitosan/oxidized dextran hydrogels for colon cancer treatment.

A sequential delivery system based on MoS2 nanoflower (MoS2 NF) doped chitosan (CS)/oxidized dextran (OD) hydrogels is developed for the treatment of colon cancer. 5-Fluorouracil (5-FU) is combined with polyethylenimine (PEI) decorated MoS2 NF via electrostatic attraction and hydrogen bonding, and the obtained 5-FU/PEI/MoS2 is encapsulated by 1-tetradecanol (TD), a commonly used phase transition material. The resultant TD/5-FU/PEI/MoS2 (TFPM) is then co-encapsulated with methotrexate (MTX) in the CS/OD hydrogels generated via Schiff base reaction and electrostatic attraction. Because the electrostatic attraction between CS and OD is pH-sensitive, MTX and TD/5-FU/PEI/MoS2 can be easily released from the hydrogels at pH 7.4. MoS2 is an outstanding photothermal agent, and the generated hyperthermia under near infrared (NIR) irradiation can lead to the melting of TD and the consequent release of 5-FU encapsulated. More importantly, the generated hyperthermia under NIR irradiation can realize the chemo-photothermal synergistic tumor therapy. Finally, the practicability of the developed sequential delivery system is demonstrated by cytotoxicity test.

A biodegradable pH and glutathione dual-triggered drug delivery system based on mesoporous silica, carboxymethyl chitosan and oxidized pullulan.

A simple and smart drug controlled delivery system is developed in this work. Biodegradable mesoporous silica nanoparticles (BMSN) were first synthesized by introducing disulfide during the synthesis of mesoporous silica nanoparticles (MSN), which were used for the loading of methotrexate (MTX), an anti-cancer drug. The MTX loaded BMSN (BMSN-MTX) was then encapsulated in the hydrogels of carboxymethyl chitosan (CMCS)/oxidized pullulan (OPL) generated through Schiff base reaction. The acylhydrazone bonds (-N=CH-) between CMCS and OPL are prone to be hydrolyzed in acidic medium while the disulfide linkage (-S-S-) in the BMSN can be cleaved in the presence of glutathione (GSH), and thus the delivery of MTX from the BMSN-MTX-gel can be triggered by both pH and GSH. The results of release kinetics reveal that the delivery of MTX from the biodegradable hydrogels is controlled by Higuchi model. Finally, good biocompatibility and pronounced cytotoxicity of the developed BMSN-MTX-gel are confirmed by cytotoxicity test.

A surface molecularly imprinted electrochemical biosensor for the detection of SARS-CoV-2 spike protein by using Cu7S4-Au as built-in probe.

Sensitive detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein (S protein) is of significant clinical importance in the diagnosis of COVID-19 pandemic. In this work, a surface molecularly imprinted (SMI) electrochemical biosensor is fabricated for the detection of SARS-CoV-2 S protein. Cu7S4-Au is used as the built-in probe and modified on the surface of a screen-printed carbon electrode (SPCE). 4-Mercaptophenylboric acid (4-MPBA) is anchored to the surface of the Cu7S4-Au through Au-SH bonds, which can be used for the immobilization of the SARS-CoV-2 S protein template through boronate ester bonds. After that, 3-aminophenylboronic acid (3-APBA) is electropolymerized on the electrode surface and used as the molecularly imprinted polymers (MIPs). The SMI electrochemical biosensor is obtained after the elution of the SARS-CoV-2 S protein template with an acidic solution by the dissociation of the boronate ester bonds, which can be utilized for sensitive detection of the SARS-CoV-2 S protein. The developed SMI electrochemical biosensor displays high specificity, reproducibility and stability, which might be a potential and promising candidate for the clinical diagnosis of COVID-19.

Fabrication of CoSe2/CoP with rich selenium- and phosphorus-vacancies and heterogeneous interfaces for asymmetric supercapacitors.

CoSe2/CoP with rich Se- and P-vacancies and heterogeneous interfaces (v-CoSe2/CoP) is grown on the surface of nickel foam via a two-step strategy: electrodeposition and NaBH4 reduction, which can be used as the cathode material in asymmetric supercapacitors. The SEM characterization reveals the honeycomb-like structure of the v-CoSe2/CoP, and the results of EPR, XPS and HRTEM reveal the existence of anionic vacancies and heterogeneous interfaces in the v-CoSe2/CoP. The as-fabricated v-CoSe2/CoP exhibits high specific capacitance (3206 mF cm-2 at 1.0 mA cm-2) and cyclic stability (91 % capacitance retention after 2000 cycles). An asymmetric supercapacitor is assembled by using the v-CoSe2/CoP and activated carbon (AC) as cathode and anode materials, respectively, which displays a high energy density of 40.6 Wh kg-1 at the power density of 211.5 W kg-1. The outstanding electrochemical performances of the v-CoSe2/CoP might be ascribed to the synergistic effects of Se- and P-vacancies and the heterogeneous interfaces in the v-CoSe2/CoP.

A highly selective and sensitive sensor for promethazine based on molecularly imprinted interface coated Au/Sn bimetal nanoclusters functionalized acupuncture needle microelectrode.

Promethazine (PMZ) is an effective antihistamine that is used as a nerve tranquilizer to treat mental disorders. However, drug abuse causes harm to the human body and also pollutes the environment to a certain extent. Therefore, it is crucial to develop a highly selective and sensitive biosensor for PMZ determination. An acupuncture needle (AN) was used as an electrode in 2015, and further research on the electrode's essence in electrochemistry is needed. In this work, a sensor based on a surface imprinted film coordinated Au/Sn biometal was first fabricated on AN via electrochemistry. The obtained cavities showed complementary and suitable sites for "N atom" electron transfer through the phenyl ring structure in promethazine, which is rigorous for the configuration near the interface. Under the optimal conditions, MIP/Au/Sn/ANE exhibits a good linear relationship in the range of 0.5 µM-500 µM, and the detection limit (LOD) is 0.14 µM (S/N = 3). The sensor exhibits good repeatability, stability, and selectivity and can be successfully used to analyze and detect PMZ in human serum and environmental water. The findings are scientifically significant for AN electrochemistry and the sensors have potential for in vivo medicamentosus monitoring in the future.

Molecularly imprinted miniature electrochemical biosensor for SARS-CoV-2 spike protein based on Au nanoparticles and reduced graphene oxide modified acupuncture needle.

Accurate detection of SARS-CoV-2 spike (SARS-CoV-2-S) protein is of clinical significance for early diagnosis and timely treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, a surface molecularly imprinted miniature biosensor was fabricated. Au nanoparticles (AuNPs), reduced graphene oxide (rGO), poly(methylene blue)/poly(ionic liquids) and poly(ionic liquids) were successively electrodeposited onto the pinpoint of an acupuncture needle (AN). The molecularly imprinted miniature biosensor was obtained after the template of SARS-CoV-2-S protein was removed, which could be used for sensitive detection of SARS-CoV-2-S protein. The linear range and limit of detection (LOD) were 0.1 âˆ¼ 1000 ng mL-1 and 38 pg mL-1, respectively, which were superior to other molecularly imprinted biosensors previously reported. The developed miniature biosensor also exhibited high specificity and stability. The reliability of the biosensor was evaluated by the detection of SARS-CoV-2-S protein in clinical serum samples.

The hybrids of perylene tetracarboxylic acid functionalized multi-walled carbon nanotubes and chitosan for electrochemical chiral sensing of tryptophan enantiomers.

To introduce abundant carboxyl (COOH) groups to the surface of multi-walled carbon nanotubes (MWCNTs) while maintaining the pristine structure of MWCNTs, 3,4,9,10-perylene tetracarboxylic acid (PTCA) was non-covalently grafted to the sidewalls of MWCNTs. The obtained PTCA functionalized MWCNTs (MWCNTs-PTCA) functioned as a scaffold for the further introduction of chitosan (CS) via electrostatic attractions and hydrogen-bonds. The resultant CS/MWCNTs-PTCA could be used for electrochemical chiral sensing of tryptophan (Trp) enantiomers due to the intrinsic chirality of CS and the high electrocatalytic activity of MWCNTs. Under optimized conditions, the Trp enantiomers could be effectively discriminated at the CS/MWCNTs-PTCA modified electrode by differential pulse voltammetry (DPV), demonstrating that the developed CS/MWCNTs-PTCA might be a potential candidate for the construction of electrochemical chiral sensors.