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Quantitative characterization of Cr 3+ , an important element revealing human metabolism and biological environmental variation, is still difficult to achieve by conventional biochemical methods due to the lack of high-sensitivity, real-time techniques with rapid response detection. Using surface-enhanced Raman scattering (SERS), we construct an Au/Ag composite-based SERS nanoprobe for the quantitative characterization of Cr 3+ content in solution, in which DL-mercaptosuccinic acid (DL-MSA) is employed for Raman signal enhancement, and 4-mercaptobenzoic acid (4-MBA) is chosen as the Raman reporter. The achieved result demonstrates obvious advantages of the synthesized Au/Ag composite-based SERS nanoprobe in sensitivity and response speed. Importantly, this Au/Ag composite-based SERS nanoprobe might provide a new strategy for dynamic monitoring of Cr 3+ content in human metabolism.

Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) are the two most important foodborne pathogens which can easily cause disease infections. Here, the aptamer-facilitated gold/silver nanodimer SERS probes were built for the simultaneous detection of the two bacteria with the help of magnetic separation enrichment. First, two nanodimer SERS signal probes and two magnetic capture probes each connected with the specific aptamer were fabricated. The distance between gold and silver nanoparticles in the dimer can amplify the Raman signal (Cy3 and Rox) at the junction but modified in the aptamer sequence. Then, after the addition of S. typhimurium and S. aureus, the sandwich-like composite structures "SERS signal probes-target-magnetic capture probes" formed because of the high affinity between aptamer sequences and their target bacteria. Under the optimal experimental conditions, the linear correlations between Raman intensity and the logarithm of the concentration of bacteria were y = 876.95x-67.84 (R 2  = 0.9865) for S. typhimurium and y = 1280.43x-1752.6 (R 2  = 0.9883) for S. aureus. The SERS detection showed the nanodimer probe had high selectivity. Besides, the recovery experiment in milk sample indicated good accuracy compared with the traditional plate counting method.

In this research, we have offered a green and new synthesizing procedure for selenium nanoparticles (Se-NPs) through the utilization of Na 2 SeO 3 , in which starch has a role of stabilizer and capping agent, as the functionality of green reducing mediums is taken by glucose and ascorbic acid. According to the observations, this method has been capable of producing Se-NPs in lab conditions. Additionally, the synthesized Se-NPs can be separated from the aqueous solution of stabilizer and reducing agents by a high-speed. Certain analyzing procedures have been used to characterize the obtained particles including TEM, XRD, UV-VIS, DLS, FESEM, EDX, FTIR, and AFM. In this paper, we have investigated the antimicrobial and photocatalytic functionality of Se-NPs on Mycobacterium tuberculosis and Methylene blue (MB) and according to the results, these particles have shown satisfying activity in both cases. To be stated in exact, about 60% of MB has degraded under UV light after 150 min, which indicates the acceptable position of Se-NPs could be applied for eliminating water pollutions. Moreover, the attained data on colorectal cancer SW480 cell lines in regards to the in vitro cytotoxicity assessments have exhibited non-toxic effects, which had lasted throughout concentrations that had measured up to even 100 µg/mL within MTT assay.

A smartphone-based dual-wavelength digital imaging platform containing red (539-695 nm) and blue (389-511 nm) band-pass filters was developed for point-of-care (POC) testing of alkaline phosphatase (ALP) activity. The platform was based on dual-emitting fluorescent nanohybrids (AuNC@NAN), the ratiometric probe, which had a fluorescence "on-off-on-off" response. The probe comprised red-emitting gold nanoclusters (AuNCs) acting as the signal report units and blue-emitting N-(2-aminoethyl-1,8-naphthalimide) (NAN) acting as an internal reference. The different responses of the ratiometric probes resulted in a continuous color-multiplexing change from pink-red to dark-purple upon exposure to ALP. The dual-wavelength digital imaging platform was employed to acquire images of AuNC or NAN fluorescence signals without the influence of background light. Unlike the classical one-time digital imaging mode, the accurate red (R) and blue (B) channel values of the generated images can help to directly judge or eliminate the disturbance from unavoidable interfering factors. The R/B values were successfully employed for determining the ALP activity at a range 2.0 to 35.0 mU·mL -1 with the detection limit of 1.04 mU·mL -1 . Such sensing imaging platform is also successful in determining ALP activity in human serum with 94.9-105% recoveries and relative standard deviation in the range 4.2-5.6%. A novel dual-wavelength smartphone-based digital imaging platform was proposed for simultaneous readout of the reporting and internal reference signals from dual-emitting ratiometric fluorescence probes, which allowed us to the accurate, reliable, and highly sensitive assay of ALP activity in complex samples.

Nanozyme based on Prussian blue nanocubes (PB NCs) loaded with copper nanoparticles (Cu@PB NCs) was synthesized. The peroxidase (POD)-like activity of Cu@PB NCs was studied and utilized for detecting the activity of alkaline phosphatase (ALP). The Cu@PB NCs possess higher POD-like activity compared with PB NCs and natural horseradish peroxidase (HRP) due to the loading of copper nanoparticles. 3,3',5,5'-Tetramethylbenzidine (TMB) can be oxidized to oxTMB in the presence of Cu@PB NCs and H 2 O 2 , generating blue-colored compound, while introduction of pyrophosphate (PPi) leads to the POD-like activity of Cu@PB NCs decreased obviously. In the presence of ALP, PPi was hydrolyzed and then the POD-like activity of Cu@PB NCs was restored. So, according to the change of the POD-like activity of Cu@PB NCs, a sensitive colorimetric assay for ALP activity was reported. The limit of detection of the assay is 0.08 mU/mL, with linear range from 0.1 to 50 mU/mL. In addition, the assay was also applied for screening the inhibitors of ALP. Nanozyme based on Prussian blue nanocube (PB NCs) loaded with copper nanoparticles was synthesized and utilized for detecting the activity of alkaline phosphatase (ALP).

A novel nanoparticle-based fluorescence probe was developed for NF-κB transcription factor detection and in situ imaging via steric hindrance. The probe contains gold nanoparticles (AuNPs) to quench fluorescence, and nucleic acids immobilized on the surface of AuNPs to output fluorescence. In the basal state, Cy5 labeled DNA1 folds its long chain into a hairpin structure and quenches fluorescence by forcing the Cy5 fluorophore close to the surface of AuNPs. After the probe enters the cell, the NF-κB transcription factor can bind to the κB site in the DNA duplex of the nucleic acids. The steric hindrance caused by NF-κB leads to the extension of the long chain of DNA1 and the removal of the Cy5 fluorophore from the surface of AuNPs, thereby restoring the fluorescence of the probe. By measuring NF-κB in cell lysis in vitro, the probe obtains a detection limit of 0.38 nM and the linear range from 0.5 to 16 nM. Repeated measurements showed the recovery in the cell nuclear extract was between 93.38 and 109.32%, with relative standard deviation less than 5%. By monitoring the sub-localization of the Cy5 fluorophore in single cell, the probe system can effectively distinguish active NF-κB (nucleus) and inactive NF-κB (cytoplasm) through in situ imaging. The well-designed probe will make up for the shortcomings of the existing technology, and reveal the regulatory role of transcription factors in many disease processes.

Accurate and rapid quantitative detection of pesticide and pollutant levels in the actual sample can aid in protecting food security, environmental security, and human health. A high Raman enhancement factor and good repeatability of the surface-enhanced Raman spectroscopy (SERS) substrates are favorable to quantitative analysis. Herein, a quantitative SERS sensor based on constructed self-assembled plasmonic Au@Ag heterogeneous nanocuboids (Au@Ag NCs) monolayer was developed. The sensor was used to quantitatively detect the trace pesticides extracted from pear surfaces and pollutants in fishpond water. Densely packed Au@Ag NCs fabricated into large-scale monolayer films were chemically functionalized using 4-methyl-thiobenzoic acid (4-MBA) at the organic/aqueous interface, in which plentiful nanogaps contribute to increase hotspots. Their sharp corners and edges make the sensor have high SERS performance through providing abundant "hot spots." The obtained optically SERS-based sensor with uniform liquid-state interfacial nanoparticle arrays appeared to have nice SERS performance and uniformity using crystal violet (CV) as a probe molecule. In particular, the proposed SERS sensor was applied for quantitative detection of thiabendazole (TBZ) extracted from pear surfaces and malachite green (MG) in fishpond water down to levels of 0.0105 nM and 0.87 nM for SERS assay respectively. As a result, our proposed SERS quantitative detection strategy is quite preferred to on-site analysis and supervision of contaminant in food samples.

A novel electrochemical DNA sensor was designed to detect Helicobacter pylori based on accordion-like Ti 3 C 2 T x . Here the multilayer Ti 3 C 2 T x obtained by DMSO delamination was used to modify the glass carbon electrode, with a large specific surface area and excellent conductivity. Au nanoparticles were supported on the modified electrode and worked as an effective carrier to fix the capture probe (cpDNA) with sulfhydryl group through the firm binding of Au-S bond. Such an accordion-like Ti 3 C 2 T x structure provides an ultrahigh electroactive surface area and ample binding sites for accommodating Au nanoparticles, which is advantageous for the signal amplification during the detection. And further, the sandwich structure formed by hybridizing cpDNA with target DNA sequence (tDNA) and rpDNA (rpDNA is a strand of DNA that can be base-paired with the tested tDNA) increases greatly the current signal and enhances the sensitivity of the electrochemical DNA sensor. Under optimal conditions, the developed electrochemical DNA sensor showed a wide linear range from 10 -11 to 10 -14  M and a low detection limit of 1.6 × 10 -16  M and exhibited good sensitivity, reproducibility, and stability. A novel electrochemical DNA sensor with simple sandwich structure was designed to detect H. pylori based on accordion-like Ti 3 C 2 T x .

Recombinase polymerase amplification (RPA) was combined with lateral flow to develop a gold nanoparticles test strip for point-of-care diagnosis of African swine fever virus (ASFV), which is called lateral flow gene assay (LFGA). Common diagnostic techniques, including polymerase chain reaction (PCR) and immunochromatography, are time-consuming and labor-intensive, and generally require costly instruments. For improvement, this assay used tailed primers to produce DNA duplexes with a single-stranded tail at one end which can hybridize with a gold nanoparticle (AuNP)-labeled oligonucleotide detection probe. And then, biotin attached to the other end of the product bound to streptavidin, which previously fixed to the test line. Therefore, there would form a sandwich structure, and gold nanoparticles labeled on the detection probe would show a red band on the test line of strip. With the low reaction temperature (37~42 °C) and short reaction time (30 min), LFGA can specifically identify ASFV in blood samples infected with ASFV and classical swine fever virus (CSFV), and the LOD was 10 2 copies/μL, which was comparable to that of agarose gel electrophoresis. In addition, blood samples infected with ASFV and CSFV were tested, and it was found that the LFGA can specifically identify ASFV DNA. In conclusion, LFGA achieves visual observation of the product after rapid RPA amplification and does not require any expensive instruments during the entire process, which is very helpful for early diagnosis of ASFV. Combined recombinase polymerase amplification (RPA) with lateral flow, we developed a gold nanoparticles test strip for point-of-care diagnosis of African swine fever virus. The upstream primers of RPA were modified with biotin, and the downstream primers were modified with a C3 spacer and an oligonucleotide tail that can be hybridized to a gold nanoparticle-labeled oligonucleotide detection probe. On the strip, the test line and control line were sprayed with streptavidin and an oligonucleotide control probe. In the presence of positive products, RPA products can form a sandwich structure on the test line. Therefore, two red lines will be displayed both on the test line and control line. When there is no positive product, only the control line is shown in red. Its low reaction temperature (37~42 °C) and short time of amplification and detection (30 min) make ASFV realizing point-of-care diagnosis in limited environment.

A dual-mode aptasensor using colorimetry and microfluidic chip (MC) together with stir bar sorptive extraction (SBSE) has been developed for firstly qualifying samples contaminated with Vibrio parahaemolyticus (V.P) and Salmonella typhimurium (S.T), then precisely determine both of them in positive samples. For this purpose, the aptamer-streptavidin encoded probes (Apt-SAEs) corresponding to different bacteria were prepared in advance. Then, a stir bar modified with 4-mercaptophenylboronic acid (MPBA) was made to extract bacteria together with Apt-SAE probes. The binding event of aptamer and target triggered the formation of two sandwich structures containing Apt-SAE, V.P or S.T. The concentration of bacteria could be enriched by 1000 times within 15 min to avoid long-time enrichment process. Finally, the stir bar was immersed in the 3,3',5,5'-Tetramethylbenzidine (TMB)-H 2 O 2 solution for color development. The color could be observed by naked eyes to judge whether the analytes were present. The colorless samples were judged to be negative. For the positive samples, the adsorbed encoded probes corresponding to different bacteria would be eluted from the stir bar and rapidly analyzed by the MC. Under the optimized conditions, 100 CFU/mL of V.P or S.T or both of them could be observed by colorimetry and 35 CFU/mL of them could be detected (S/N = 3) by the MC. The assay has significant application value for on-site screening and multiple detection of food-borne pathogenic bacteria.

Pathogenic bacteria have become a huge threat to social health and economy for their frighteningly infectious and lethal capacity. It is quite important to make a diagnosis in advance to prevent infection or allow a rapid treatment after infection. Noble metal nanoparticles, due to their unique physicochemical properties, especially optical properties, have drawn a great attention during the past decades and have been widely applied into all kinds of fields related to human health. By utilizing these noble metal nanoparticles, optical diagnosis platforms towards pathogenic bacteria have emerged continually, providing highly sensitive, selective, and particularly facile detection tools for clinic or point-of-care diagnosis. This review summarizes the recent development in this field. It begins with a brief introduction of pathogenic bacteria and noble metal nanoparticles. And then, optical detection methods are systematically discussed in three distinct aspects. In addition to these proof-of-concept methods, corresponding algorithms and point-of-care detection devices are also described. Finally, the review ends up with subjective views on present limitations and some appropriate advice for future research directions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An ultrasensitive electrochemical sensor has been constructed for the detection of single nucleotide polymorphisms (SNPs) based on DNA-functionalized Cd-MOFs-74 as cascade signal amplification probe under enzyme-free conditions. Interestingly, the introduction of an auxiliary probe did not disturb the detection of SNP targets, but could bind more Cd-MOFs-74 signal elements to enhance the different pulse voltammetry electrochemical signal 2~3 times as compared to sensing system without auxiliary probe, which obviously improves the sensitivity of the proposed sensor. Experimental results taking p53 tumor suppressor gene as SNP model demonstrated that the proposed method can be employed to sensitively and selectively detect target p53 gene fragment with a linear response ranging from 0.01 to 30 pmol/L (detection limit of 6.3 fmol/L) under enzyme-free conditions. Utilizing this strategy, the ultrasensitive SNP electrochemical sensor is a promising tool for the determination  of SNPs in biomedicine. Graphical Abstract., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Highly negatively charged gold nanoparticles (AuNPs) are shown to have strong simulated oxidase activity and effectively boosted the oxidation of enzyme substrate 3,3',5,5'-tetramethylbenzidine (TMB) by hexavalent chromium ion Cr(VI), resulting in the formation of oxidation product with blue color. Based on this, a facile colorimetric assay was developed to detect Cr(VI) at a range 0.008~0.156 mg/L with r = 0.996. The detection limit was estimated to be 0.52 μg/L. In addition, the colorimetric assay showed high selectivity against 28 other interfering ions. It was performed at room temperature and required about half an hour including the preparation of AuNPs. The assay was successfully applied to the determination of Cr(VI) in spiked water samples, and recoveries in the range 95.00-105.40% were obtained. This work paves a way for design of high performance sensor based on highly active nanozymes and also provides an extremely practical analytical tool for the monitoring of Cr(VI) in the environment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Platinum-containing nanozymes with peroxidase-mimicking activity (PMA) have found a broad application in bioanalytical methods and are potentially able to compete with enzymes as the labels. However, traditionally used methods for the synthesis of nanozymes result in only a small fraction of surface-exposed Pt atoms, which participate in catalysis. To overcome this limitation, we propose a new approach for the synthesis of nanozymes with the efficient dispersion of Pt atoms on particles' surfaces. The synthesis of nanozymes includes three steps: the synthesis of gold nanoparticles (Au NPs), the overgrowth of a silver layer over Au NPs (Au@Ag NPs, 6 types of NPs with different thicknesses of Ag shell), and the galvanic replacement of silver with PtCl 6 2- leading to the formation of trimetallic Au@Ag-Pt NPs with uniformly deposited catalytic sites and high Pt-utilization efficiency. Au@Ag-Pt NPs (23 types of NPs with different concentrations of Pt) with various sizes, morphology, optical properties, and PMA were synthesized and comparatively tested. Using energy-dispersive spectroscopy mapping, we confirm the formation of core@shell Au@Ag NPs and dispersion of surface-exposed Pt. The selected Au@Ag-Pt NPs were conjugated with monoclonal antibodies and used as the colorimetric and catalytic labels in lateral flow immunoassay of the inflammation biomarker: C-reactive protein (CRP). The colorimetric signal enhancement was achieved by the oxidation of 3,3'-diaminobenzidine by H 2 O 2 catalyzed by Au@Ag-Pt NPs directly on the test strip. The use of Au@Ag-Pt NPs as the catalytic label produces a 65-fold lower limit of CRP detection in serum (15 pg mL -1 ) compared with Au NPs and ensures the lowest limit of detection for equipment-free lateral flow immunoassays. The assay shows a high correlation with data of enzyme-linked immunosorbent assay (R 2 = 0.986) and high recovery (83.7-116.2%) in serum and plasma. The assay retains all the benefits of lateral flow immunoassay as a point-of-care method., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Diagnosis of bacterial infections (BI) is becoming an increasingly difficult task in clinical practice due to their high prevalence and frequency, as well as the growth of antibiotic resistance worldwide. World Health Organization (WHO) reported antibiotic resistance is a major public health problem. BI becomes difficult or impossible to treat when the bacteria acquire immunity against antibiotics. Thus, there is a need for a quick and accurate technique to detect infection. Lateral flow immunoassay (LFIA) is an ideal technique for point-of-care testing of a disease or pathological changes inside the human body. In recent years, several LFIA based strips are being used for the detection of BI by targeting specific analytes which may range from the causative bacterium, whole-cell, DNA, or biomarker. Numerous nanoparticles like lipid-based nanoparticles, polymeric nanoparticles, and inorganic nanoparticles such as quantum dots, magnetic, ceramic, and metallic nanoparticles (copper, silver gold, iron) are widely being used in the advanced treatment of BI. Out of these gold nanoparticle (AuNPs), is being used for detection BI more effectively than other nanoparticles due to their surface functionalization, extraordinary chemical stability, biorecognition, and signal amplification properties and help to improve in conjugation with capture antibodies, and act as a color marker with unique optical properties on LFIA strips. Herein, a review that provides an overview of the principle of LFIA, how LFIA based strip is developed, and how it is helpful to detect a specific biomarker for bedside detection of the BI., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Palladium nanoparticles (PdNPs) are composed mainly of inert noble metals, and their outstanding properties have attracted wide attention. PdNPs are not only capable of mimicking the oxidase-like characteristics of natural bio-enzymes, but they also present a clear black band in the test zone. In this work, the synthesized PdNPs promoted a transformation of colorless tetramethylbenzidine (TMB) to a blue oxidation product of TMB, providing a K m value of 0.09 mM for TMB, and revealing the good catalytic performance of the synthesized PdNPs. For both signal generation and amplification, PdNPs effectively replaced natural bio-enzymes as a new labeling tag. Thus, the PdNP-based enzyme-free single-step immunoassays were successfully developed for efficient and sensitive detection of glycocholic acid (GCA). Under optimal conditions, a noticeable linear relationship was identified by the enzyme-linked immunosorbent assay (ELISA) over a range of 8-2390 ng/mL, while the visual limit of detection (vLOD) in the constructed lateral flow immunoassay (LFA) was 10 ng/mL for GCA. The recovery rate in spiked urine samples obtained by the ELISA ranged from 84.2 to 117.9%, which was consistent with the results in LFA. The present work demonstrates the potential of PdNPs as labeling matrices in enzyme-free single-step immunoassays., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel cytosensor was constructed for the ultrasensitive detection and nondestructive release of circulating tumor cells (CTCs) by combining Au nanoparticles-loaded two-dimensional bimetallic PdMo (2D Au@PdMo) nanozymes and electrochemical reductive desorption. The 2D Au@PdMo nanozymes possessed high-efficiency peroxidase-like activity and were assembled with an aptamer composed of a thiol-modified epithelial specific cell adhesion molecule (EpCAM) to strengthen CTCs adhesion. Moreover, the electrode surface was decorated with highly fractal Au nanostructures (HFAuNSs) composites due to the similarity in fractal nanostructure with the CTCs membrane to enhance the CTCs anchoring efficiency and release capability. The captured CTCs could be further efficiently dissociated and nondestructively released from the modified electrodes upon electrochemical reductive desorption. The designed cytosensor showed an excellent analytical performance, with a wide linear range from 2 to 1 × 10 5 cells mL -1 and low limit of detection (LOD) of 2 cells mL -1 (S/N = 3) at the working potential in the range  -0.6 to 0.2 V. A satisfactory CTCs release reaching a range of 93.7-97.4% with acceptable RSD from 3.55 to 6.41% and good cell viability was obtained. Thus, the developed cytosensor might provide a potential alternative to perform CTC-based liquid biopsies, with promising applications in early diagnosis of tumors. Preparation and mechanism of desorption of the cytosensor based on 2D Au@PdMo nanozymes and electrochemical reductive desorption for the detection and release of CTCs. A Preparation procedure of the Apt/Au@PbMo bioconjugates. B Fabrication process of the sandwich-type cytosensor. C Electrochemical signal produced by the Au@PdMo nanozymes. D Mechanism of electrochemical reductive desorption for CTCs release., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A sensitive on-site mercury sensing platform was developed for simple and effective monitoring of mercury levels in the field. The simple and practical mercury detection system was designed by integrating an Au nanoparticle-PEG hydrogel block nanozyme (Au-HBNz) into a polymer film-based colorimetric device. Upon addition of Hg 2+ ions, Au-HBNz exhibited excellent peroxidase-like activity, catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine into a blue-colored product, which has a maximum absorbance at 652 nm. The resulting color intensity change was evaluated using a smartphone for simple and rapid Hg 2+ detection with a broad detection range (0.008-20 μg∙mL -1 ) and a linear concentration-response relationship (R 2  = 0.96). The detection limit (1.10 ng∙mL -1 ) was lower than the maximum permissible Hg 2+ levels in drinking water set by the World Health Organization (6 ng∙mL -1 ) and U.S. Environmental Protection Agency (2 ng∙mL -1 ). The recoveries of Hg 2+ determination in river water by spiking Hg 2+ samples ranged from 92 to 106%, which indicated high validity and applicability of the Hg 2+ detection system for field measurements. Thus, the developed sensor enables highly selective and efficient real-time monitoring of Hg 2+ ., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

As an ideal substitute for traditional organic fluorescent dyes or up-conversion nanomaterials, copper nanoclusters (CuNCs) have developed rapidly and have been involved in exciting achievements in versatile applications. The emergence of novel CuNCs composites improves the poor stability and fluorescence intensity of CuNCs. With this in mind, great efforts have been made to develop a wide variety of CuNCs composites, and impressive progress has been made in the past few years. In this review, we systematically summarize absorption, fluorescence, electrochemiluminescence, and catalytic properties and focus on the multiple factors that affect the fluorescence properties of CuNCs. The fluorescence properties of CuNCs are discussed from the point of view of core size, surface ligands, self-assembly, metal defects, pH, solvent, ions, metal doping, and confinement effect. Especially, we illustrate the research progress and representative applications of CuNCs composites in bio-related fields, which have received considerable interests in the past years. Additionally, the sensing mechanism of CuNCs composites is highlighted. Finally, we summarize current challenges and look forward to the future development of CuNCs composites. Schematic diagram of the categories, possible sensing mechanisms, and bio-related applications of copper nanoclusters composites., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Butyrylcholinesterase (BChE) is an important indicator for clinical diagnosis of liver dysfunction, organophosphate toxicity, and poststroke dementia. Point-of-care testing (POCT) of BChE activity is still a challenge, which is a critical requirement for the modern clinical diagnose. A portable photothermal BChE assay is proposed through modulating the photothermal effects of Cu 2 O nanoparticles. BChE can catalyze the decomposition of butyrylcholine, producing thiocholine, which further reduce and coordinate with CuO on surface of Cu 2 O nanoparticle. This leads to higher efficiency of formation of Cu 9 S 8 nanoparticles, through the reaction between Cu 2 O nanoparticle and NaHS, together with the promotion of photothermal conversion efficiency from 3.1 to 59.0%, under the excitation of 1064 nm laser radiation. An excellent linear relationship between the temperature change and the logarithm of BChE concentration is obtained in the range 1.0 to 7.5 U/mL, with a limit of detection of 0.076 U/mL. In addition, the portable photothermal assay shows strong detection robustness, which endows the accurate detection of BChE in human serum, together with the screening and quantification of organophosphorus pesticides. Such a simple, sensitive, and robust assay shows great potential for the applications to clinical BChE detection and brings a new horizon for the development of temperature based POCT., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An efficient electrogenerated chemiluminescence (ECL) nanoprobe (luminol-Au NPs-Ti 3 C 2 ) was constructed based on Ti 3 C 2 Tx MXene (Ti 3 C 2 )-mediated in situ formation of Au NPs and anchoring luminol to fabricate a sensitive ECL biosensor for miRNA-155 detection. Herein, Ti 3 C 2 with rich Ti vacancy defects was used as reducing agent, and Au NPs were generated in situ and anchored on the Ti 3 C 2 (Au NPs-Ti 3 C 2 ). Moreover, the Au NPs-Ti 3 C 2 composites were used as a carrier and provided a large number of sites for the efficient linking of luminol through Au-N bonds to form stable luminol-Au NPs-Ti 3 C 2 . The immobilization of ECL emitters is a versatile strategy which not only shortens the electron transmission distance between luminol and electrode, but also provides naked catalytic predominated (111) facets of Au NPs with high electrocatalytic activity, significantly improving the ECL signal of luminol. Furthermore, a catalytic hairpin assembly (CHA) reaction was used, resulting in further amplification of the signal. As a result, the as-prepared ECL biosensor exhibited a linear range from 0.3 fM to 1 nM with a detection limit of 0.15 fM, and demonstrated high reliability of miRNA-155 detection even in human serum samples. The construction of a multifunctional ECL probe with excellent ECL emission opens a new chapter for the application of Ti 3 C 2 in the field of bioanalysis. Herein, Au NPs were generated in situ and anchored on the Ti 3 C 2 (Au NPs-Ti 3 C 2 ). Moreover, the Au NPs-Ti 3 C 2 was used as a carrier and linked luminol through Au-N bonds to form a stable luminol-Au NPs-Ti 3 C 2 nanoprobe. The strategy displayed versatility which not only shortened the electron transmission distance between luminol and the electrode, but also provided a catalytic surface with high electrocatalytic activity of Au NPs that significantly improved the ECL signal of luminol., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Raman spectroscopy is a powerful method to characterize molecules in various media. Although surface-enhanced Raman scattering (SERS) is often employed to compensate for the intrinsically poor sensitivity of Raman spectroscopy, there remain serious tasks, such as simple preparations of SERS substrates, sensitivity control, and reproducible measurements. Here, we propose freezing as an efficient way to overcome these problems in SERS measurements using DNA bases as model targets. Solutes are expelled from ice crystals and concentrated in the liquid phase upon freezing. Silver nanoparticles (AgNPs) are also concentrated in the liquid phase to aggregate with Raman target analytes. The SERS signal intensity is maximized when the AgNP concentration exceeds the critical aggregation value. Freezing allows up to 5000 times enhancements of the SERS signal. Thus, an efficient SERS platform is prepared by simple freezing. The simultaneous detection of four DNA bases effectively eliminates variations of signal intensities and allows the reliable determination of concentration ratios., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Horseradish peroxidase (HRP) was highly loaded into large holes of nanometer-scale metal-organic frameworks (i.e., PCN-333(Al)) for signal amplification in enzyme-linked immunosorbent assay (ELISA). The enzyme-labeled antibody complex prepared using nanometer-scale PCN-333(Al) maintained a high catalytic efficiency. Its V m and K cat values with 3,3',5,5'-Tetramethylbenzidine (TMB)-H 2 O 2 as substrates were 4.84 × 10 -5  mM/s and 4.84 × 10 4  min -1 , respectively. We demonstrated an HRP@PCN-333 signal amplification strategy for colorimetric assay of human prostate-specific antigen (PSA). The linear range of PSA detection by using this method was 15-165 pg/mL, and the limit of detection was 6 pg/mL (S/N = 3), indicating the potential application of this method in detecting disease markers under clinical conditions. The presented strategy exhibited the characteristics of significantly increased amount of labeled enzymes, improved stability and utilization of enzymes, simple preparation process of enzyme-labeled antibodies, and low cost., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cefepime and Meropenem are the new class of antibiotics, which are particularly used as last potent defender or the antibiotics of the last resort against multi-resistant bacterial species. In this paper, an impedance-based electrochemical biosensor was fabricated for identifying antibiotics of last resort in the forensic samples including gastric lavage and other body fluids. The sensor was developed using platinum nanoparticles (PtNPs) and electrodeposited zinc oxide- zinc hexacyanoferrate hybrid film (ZnO/ZnHCF) on the surface of a fluorine-doped glass electrode (FTO). Further, penicillinase was immobilized onto the modified electrode using penicillinase enzyme. The developed biosensor exhibits a good analytical response for the detection of antibiotics evaluated using electrochemistry studies. The linear response of the fabricated electrode was observed from 0.1 to 750 µM and the electrode limit of detection (LOD) was observed as 0.1 µM. The sensor confirms good accuracy, is highly selective, and sensitive for the target. While storing the modified electrode at 4 °C, the stability of biosensor was evaluated for 45 days, and activity loss of 30-40% was observed. The highly sensitive interface of Penicillinase@CHIT/PtNP-ZnO/ZnHCF/FTO electrode shows a promising future in forensic studies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A sensitive detection of carbohydrate antigen 15-3 (CA15-3) levels may allow for early diagnosis and monitoring the treatment of breast cancer, but this can only be made in routine clinical practice if low-cost immunosensors are available. In this work, we developed a sandwich-type electrochemical immunosensor capable of rapid detection of CA15-3 with an ultra-low limit of detection (LOD) of 0.08 fg mL -1 within a wide linear concentration range from 0.1 fg mL -1 to 1 µg mL -1 . The immunosensor had a matrix of a layer-by-layer film of Au nanoparticles and reduced graphene oxide (Au-rGO) co-electrodeposited on screen-printed carbon electrodes (SPCE). The high sensitivity was achieved by using secondary antibodies (Ab 2 ) labeled with horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H 2 O 2 ) as signal amplifiers, and hydroquinone (HQ) was used as an electron mediator. The immunosensor was selective for CA15-3 in human serum and artificial saliva samples, robust, and stable to permit storage at 4 °C for more than 30 days. With its high performance, the immunosensor may be incorporated into future point-of-care (POC) devices to determine CA15-3 in distinct biological fluids, including in blood and saliva samples., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The current trends in modern medicine towards early diagnosis, or even prognosis, of different diseases have brought about the need for the corresponding biomarker detection at ever lower levels in really complex matrices. To do so, it is necessary to use proper extremely sensitive detection techniques such as elemental mass spectrometry. However, target labelling with metals for subsequent sensitive ICP-MS detection falls short nowadays even if resorting to inorganic nanoparticles containing a high number of detectable elements. Thus, new amplification strategies are being proposed to face this analytical challenge that will be critically discussed in this paper. Fundamentals of different novel strategies developed to achieve signal amplification and sensitive elemental mass spectrometry detection are here discussed. Some representative examples of relevant clinical applications are highlighted, along with future prospects and challenges., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

As a paper-based analytical platform, lateral flow assay (LFA) gets benefit from the rapid analysis, low cost, high selectivity, good stability, and user-friendliness, and thus has been widely used in rapid screening or assisted diagnosis. Nevertheless, LFA still suffers from low detection sensitivity via the naked eye, limiting its applications to qualitative and semi-quantitative tests. To enhance the signal readout, various nanoparticle signal tags have been employed to replace traditional colloidal gold nanoparticles (AuNPs), such as fluorescent nanoparticles (FNPs), magnetic nanoparticles (MNPs), and Raman reporter-labeled nanoparticles. In particular, Raman reporter-labeled nanoparticles are extremely sensitive due to remarkable signal enhancement effect on metal surface. However, the application of LFA is still hampered by the poor stability of Raman reporter-labeled nanoparticles. Herein, we developed an in situ Raman enhancement strategy to create a surface-enhanced Raman scattering (SERS) signal on the AuNPs, shortened as "i-SERS," which not only preserves the original advantages of the colloidal gold strip (AuNPs-LFA), but also realizes highly sensitive and quantitative detection. We applied the i-SERS for procalcitonin (PCT) detection. The experimental process takes only 16 min, and the limit of detection (LOD) is 0.03 ng mL -1 , far below the value using AuNPs-LFA. These results indicate that i-SERS assay was highly sensitive and suitable for the rapid detection of PCT., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

A sandwich electrochemical biosensing strategy for ultrasensitive detection of miRNA-21 was developed by using graphene oxide incorporated 3D-flower-like MoS 2 (3D MoS 2 -rGO) nanocomposites as the substrate and horseradish peroxidase (HRP)-functionalized DNA strand 1 (S1)-gold nanoparticles (S1-AuNPs-HRP) as signal amplification probes. Herein, 3D MoS 2 -rGO nanocomposites not only had a large specific surface area and excellent conductivity, but also provided more attachment sites for electrodepositing AuNPs. In the presence of target miRNA, a sandwich structure was formed, and the determination of the miRNA-21 was carried out by measuring the DPV response of H 2 O 2 mediated by hydroquinone (HQ) at a potential of + 0.052 V (vs AgCl reference electrode). Under the optimal experimental conditions, the as-prepared biosensor enabled the ultrasensitive detection of miRNA-21 from 5 fM to 0.5 μM with the low detection limit of 0.54 fM (S/N = 3), comparable or lower than previous reported methods for miRNA-21 detection, which benefited from the synergistic amplification of 3D MoS 2 -rGO and AuNPs-HRP. The prepared biosensor showed satisfactory selectivity, reproducibility, and stability towards miRNA-21 detection. The biosensor was feasible for accurate and quantitative detection of miRNA-21 in normal human serum samples with RSD below 5.86%, which showed a great potential in clinical analysis and disease diagnosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The simple and reliable detection of microRNAs is of great significance for studying the biological functions, molecular diagnosis, disease treatment and targeted drug therapy of microRNA. In this study, we introduced a novel Ti 3 C 2 Tx (MXene) aerogels (denoted as MXA) composite gold nano-particles (AuNPs)-modified disposable carbon fiber paper (CFP) electrode for the label-free and sensitive detection of miRNA-155. Firstly, in the presence of MXene, graphene oxide (GO) and ethylenediamine (EDA), the 3D MXene hydrogel was formed by self-assembly method, and then adding the freeze-dried 3D MXA dropwise to CFP. Subsequently, electrodepositing AuNPs on the CFP/MXA was done to construct a 3D disposable DNA-circuit test strip with excellent interface. Under the optimum experimental conditions, the detection limit of 3D disposable DNA circuit strip for miRNA-155 was 136 aM (S/N = 3). The CFP/MXA/AuNPs (CMA) electrode also has a wide dynamic range (20 fM to 0.4 μM), with a span of 4 orders of magnitude. Notably, we also tested the practicality of the sensor in 8 clinical samples. The technological innovations in the detection and quantification of microRNA in this work may be helpful to the study new aspects of microRNA biology and the development of diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Chains of nickel nanoparticles coated with few nitrogen-doped graphitic carbon layers (Ni@NC) are synthesized by hydrogen-assisted pyrolysis of Ni-ZIF. Hydrogen and temperature can play key roles in the formation of oriented Ni@NC nanoparticle chains, and carbon shells can protect Ni nanoparticles from external oxidation and aggregations. Under the optimized potential (0.60 V vs. Ag/AgCl), the Ni@NC7H nanoparticle chains obtained at 700 °C under H 2 /Ar atmosphere (Ni@NC7H) demonstrate outstanding performances, such as high sensitivity of 1.44 mA mM -1  cm -2 (RSD = 1.0%), low detection limit of 0.34 μM (S/N = 3), broad linear range from 1 μM to 1.81 mM, and excellent application potential in artificial sweat and human serum. Therefore, the findings above indicate that this study will provide a general methodology for the synthesis of chains-like core-shell nanoparticle electrocatalysts for non-enzymatic glucose detection., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In this paper, novel synergetic PtNP@Co 3 O 4 hollow nanopolyhedrals with peroxidase-like activities are designed and prepared, which can be used as electrochemical and colorimetric signal labels for the enzyme-free dual-channel homogeneous sensing of prostate-specific antigen. When prostate-specific antigens are present, the aptamer-modified PtNP@Co 3 O 4 hollow nanopolyhedrals and magnetic beads form sandwich structures, which have excellent peroxidase-like activities, because of the synergetic effect of PtNP@Co 3 O 4 hollow nanopolyhedrals. The sandwich structures can be separated from the mixture by the magnetic effect of the magnetic beads and catalyze the redox reactions between H 2 O 2 and TMB, generating quantitative electrochemical and colorimetric responses in homogeneous solution simultaneously. Under the optimized conditions, the linear range of both electrochemical (0.01 to 10 ng/ml) and colorimetric (0.01-15 ng/ml) channels can satisfy the demand of prostate-specific antigen detection in clinic (4 ng/ml), and the electrochemical and colorimetric channels have a low detection limit of 0.0079 ng/ml and 0.01 ng/ml respectively without using natural enzymes. The strategy by using synergetic PtNP@Co 3 O 4 hollow nanopolyhedrals as signal probes provides a promising scheme for developing simple, rapid, reliable, and ultrasensitive dual-channel homogeneous biosensors, which has a great potential as a powerful tool in prostate cancer diagnosis., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

This work presents the realization of a label-free electrochemical immunosensor for the quick, cheap, and straightforward determination of atrazine. This biodevice is based on developing a technological platform where a gold screen printed electrode (Au-SPE) surface was modified by the electrodeposition of a highly porous gold layer. As an internal probe redox, a Prussian Blue thin layer (PB) was then electrosynthetized onto the modified Au-SPE. Atrazine antibody (Ab-ATZ) was immobilized using G protein-functionalized magnetic nanoparticles (MNPs@protG) to ensure the correct orientation of the antibody to enhance the immunoaffinity. Under optimum experimental conditions, the electrochemical characterization of the developed immunosensor displays a linearity range towards atrazine within 0.05-1.5 ng/mL, a LOD of 0.011 ng/mL good reproducibility and stability. The immunosensor was tested in the analysis of spiked drinking water samples with a mean recovery ranging from 95.7 to 108.4%. The overall good analytical performances of this immunodevice suggest its application for the screening and monitoring of atrazine in real matrices., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Precise evaluation of telomerase activity is essential for the clinical diagnosis of early tumors. Herein, we have ingeniously designed a tetrahedral DNA nanostructure, with hairpin-shaped DNA probes rich in cytosine bases at four vertices for telomerase detection. The DNA-templated silver nanoclusters can be formed after the addition of Ag. Then the introduction of telomerase adds the single-strand TTAGGG extension, which can "turn on" the fluorescence of silver nanoclusters quickly by the proximity of the resulting guanine-rich sequences to silver nanoclusters and realize accurate detection of telomerase activity. In this study, integration of high stability tetrahedral DNA nanostructure and fluorescence signal amplification of four DNA-templated silver nanoclusters offers the advantage of high sensitivity, with a low detection limit of 1 cell. More than that, this method is low-cost, facile, and feasible for practical clinical applications., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Abscisic acid (ABA), as the most common plant hormone in the growth of wheat, can greatly affect the yield when its levels deviate from normal. Therefore, highly sensitive and selective detection of this hormone is greatly needed. In this work, we developed an aptamer sensor based on surface-enhanced Raman spectroscopy (SERS) and applied it for the high sensitivity detection of ABA. Biotin-modified ABA aptamer complement chains were modified on ferrosoferric oxide magnetic nanoparticles (Fe 3 O 4 MNPs) and acted as capture probes, and sulfhydryl aptamer (SH-Apt)-modified silver-coated gold nanospheres (Au@Ag NPs) were used as signal probes. Through the recognition of the ABA aptamer and its complementary chains, an aptamer sensor based on SERS was constructed. As SERS internal standard molecules of 4-mercaptobenzoic acid (4-MBA) were encapsulated between the gold core and silver shell of the signal probes; the constructed aptamer sensor generated a strong SERS signal of 4-MBA after magnetic separation. When there were ABA molecules in the detection system, with the preferential binding of ABA aptamer and ABA molecule, the signal probes were released from the capture probes, after magnetic separation, leading to a linear decrease in SERS intensity of 4-MBA. Thus, the detection response was linear over a logarithmic concentration range, with an ultra-low detection limit of 0.67 fM. In addition, the practical use of this assay method was demonstrated in ABA detection from fresh wheat leaves, with a relative error (RE) of 5.43-8.94% when compared with results from enzyme-linked immunosorbent assay (ELISA). The low RE value proves that the aptamer sensor will be a promising method for ABA detection., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel electrochemiluminescence (ECL) biosensor for the determination of microRNA-21 (miRNA-21) was developed, based on a hybrid luminescent Co-MOF-ABEI/Ti 3 C 2 T x composite as an ECL luminophore combined with a duplex-specific nuclease (DSN)-assisted signal amplification strategy. The synthesized Co-MOF-ABEI/Ti 3 C 2 T x composite carrying N-(4-aminobutyl)-N-ethylisoluminol (ABEI) exhibited strong and stable ECL in the presence of reactive oxygen species (ROS). The ECL biosensor was fabricated by adsorbing Co-MOF-ABEI/Ti 3 C 2 T x onto a glassy carbon electrode and covalently coupling the probe DNA onto the surface of the Co-MOF-ABEI/Ti 3 C 2 T x -modified electrode. In the presence of the target miRNA-21, the DSN selectively cleaved the complementary DNA section (S1) to miRNA-21, resulting in the release of the transduction section (S2) and the reuse of miRNA-21 in the subsequent amplification cycle. The interaction of the stem-loop structure of the probe DNA with the Co-MOF-ABEI/Ti 3 C 2 T x -modified glassy carbon electrode with S2 strands led to the opening of the annular part of the probe DNA. Then, the opened guanine (G)-rich sequences of probe DNA were exposed and folded into a hemin/G-quadruplex DNAzyme in the presence of hemin. The catalysis of H 2 O 2 to ROS by the hemin/G-quadruplex DNAzyme significantly enhanced ECL intensity, and this intensity was logarithmically proportional to the concentration of target miRNA-21 between 0.00001 and 10 nM, having a limit of detection of 3.7 fM. The designed ECL biosensor can  detect miRNA-21 extracted from HeLa cells, indicating its promising application in clinical diagnosis and disease prognosis analysis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A photoelectrochemical (PEC) biosensor based on a multiple signal amplification strategy was established for highly sensitive detection of microRNA (miRNA). TiO 2 was prepared on the surface of titanium sheet by laser etching to improve its stability and photoelectrical properties, and CuInS 2 -sensitized TiO 2 was used to form a superior photoelectrical layer, which realized the initial signal amplification. The electron donor dopamine (DA) was modified to H2 as a signal regulator, which effectively increased the photocurrent signal. To further amplify the signal, an enzyme-free hybridization reaction was implemented. When target let-7a and fuel-DNA (F-DNA) were present, the base of H1 specifically recognized let-7a and forced dopamine@AuNPs-H2 away from the electrode surface. Subsequently, the end base of H1 specifically recognized F-DNA, and let-7a was replaced and recycled to participate in the next cycle. Enzyme-free circulation, as a multifunctional amplification method, ensured the recycling of target molecules. This PEC sensor for let-7a detection showed an excellent linear response from 0.5 to 1000 pM with a detection limit of 0.12 pM. The intra-batch RSD was 3.8% and the recovery was 87.74-108.1%. The sensor was further used for clinical biomolecular monitoring of miRNA, showing excellent quantitative detection capability., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A method is described to achieve accurate quantitative detection of atrazine (ATZ) in maize by using lateral flow strips based on gold nanoparticles (GNPs) and a handheld scanning reader. GNPs of 15 nm in diameter were applied as label, and a lateral flow immune assay strip was prepared. The linear range was 5.01-95.86 ng mL -1 with a detection limit of 4.92 ng mL -1 in phosphate buffer, 4 times better than the readout by the naked eye. ATZ-spiked corn samples were also analysed. The accuracy of results of spiked samples was confirmed by ELISA and liquid chromatography-tandem mass spectrometry (HPLC), which proved the reliability of the proposed method. A handhold device with an optical scanning system was designed for on-site quantitative detection. Combined with the pretreatment, the assay could be completed in less than 20 min., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An electrochemiluminescence (ECL) aptasensor for the detection of the milk protein allergen β-lactoglobulin (β-LG) using nanocomposite as luminophore was fabricated. The Ru-AuNPs/GNP/Naf complex was formed by combining the Rubpy 3 2+ -AuNPs complex (Ru-AuNPs), prepared by modifying the negatively charged surface of gold nanoparticles (AuNPs) with positively charged Rubpy 3 2+ through electrostatic interactions and the graphene nanoplatelets-Nafion (GNP/Naf) at a ratio of 2:1. The nanocomposite was coated on the surface of the screen-printed electrode (SPCE) through the film-forming properties of Nafion. A layer of chitosan (CS) was coated onto this modified electrode, and later amine-terminated β-LG aptamers were covalently attached to the CS/Ru-AuNP/GNP/Naf via glutaraldehyde (GLUT) cross-linking. When β-LG was incubated with the aptasensor, a subsequent decrease in ECL intensity was recorded. Under the optimal conditions, the ECL intensity of the aptasensor changed linearly with the logarithmic concentration of β-LG, in the range 0.1 to 1000 pg/ml, and the detection limit was 0.02 pg/mL (3σ/m). The constructed aptasensor displayed simple and fast determination of β-LG with excellent reproducibility, stability, and high specificity. Additionally, the proposed ECL aptasensor displayed high recoveries (92.5-112%) and low coefficients of variation (1.6-7.8%), when β-LG fortified samples were analyzed. Integrating Ru-AuNPs/GNP/Naf nanocomposite in the ECL aptasensor paves the way towards a cost-effective and sensitive detection of the milk allergen β-LG., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

C-Reactive protein (CRP) is a biomarker of inflammatory responses and an index for assessing the risk of cardiovascular disease and estimating prognosis. In this study, we constructed a surface-enhanced Raman spectroscopy (SERS) biosensor composed of a multifunctional DNA three-way junction (DNA 3WJ), porous gold nanoplates (pAuNPs), and an Au-Te nanoworm structure for detection of CRP. The pAuNP and Au-Te nanostructures were synthesized by galvanic replacement reactions, and the morphology was confirmed by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering (DLS). To generate the SERS signal, the Au-Te nanostructure was immobilized on an indium-tin oxide substrate, and the thiol-modified CRP aptamer was then self-assembled onto the modified substrate for CRP recognition. To amplify the SERS signal and identify the Raman tag, the multifunctional DNA 3WJ was conjugated with the pAuNPs, and each fragment of 3WJ was functionalized to biotin (pAuNP conjugation), methylene blue (Raman reporter), and CRP aptamer (target binding). The results were confirmed by gel electrophoresis. For conjugation between pAuNPs and DNA 3WJ, avidin was encapsulated in pAuNPs, and the conjugation structure was confirmed by DLS. The fabricated SERS biosensor showed detection limits of 2.23 pM in phosphate-buffered saline and 3.11 pM in diluted human serum. Overall, the proposed biosensor may have potential applications as a SERS biosensor platform., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel ratiometric electrochemical sensor was developed based on a carbon cloth electrodeposited with silver nanoparticles and drop-coated by covalent organic framework (COF-LZU1) for simultaneous determination of bisphenol A (BPA) and bisphenol S (BPS). Carbon cloth exhibited a significantly larger electrochemical active area than common glassy carbon electrodes (27.5 times). Silver nanoparticles not only provided a stable reference signal but also enhanced electroactivity for the oxidation of BPA and BPS. COF-LZU1 with good adsorption performance and large periodic π-arrays promoted the enrichment of BPA and BPS to further increase the current response. Compared with the traditional single-signal electrochemical sensor, the developed ratiometric sensor exhibited better reproducibility and a wider linear range for BPA and BPS from 0.5 to 100 μM with a limit of detection of 0.15 μM. Furthermore, the developed sensor showed excellent stability and superior anti-interference ability. The real sample analysis for BPA and BPS has been successfully carried out in mineral water, electrolyte drink, tea, juice, and beer with recoveries of 88.3-111.7%. The developed ratiometric sensor is expected to be a candidate for the preparation of other electrochemical sensors and the analysis of additional practical samples., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Chlorpyrifos is one of the most widely used organophosphate insecticides in agricultural production. Nevertheless, the residues of chlorpyrifos in agricultural by-product seriously threaten human health. Thus, the ultrasensitive detection of chlorpyrifos residues in agri-food products is of great demand. Herein, an AuNP/HNT-assembled disposable paper SERS substrate was prepared by an electrostatic self-assembly method to detect chlorpyrifos residues. The AuNP/HNT paper substrate exhibited high SERS activity, good reproducibility, and long-term stability, which was successfully used for quantitative detection of chlorpyrifos; the detection limit reached 7.9 × 10 -9  M. For spiked apple samples the calculated recovery was 87.9% with a RSD value of 6.1%. The excellent detection ability of AuNP/HNT paper-based SERS substrate indicated that it will play an important role in pesticide detection in the future. AuNP/HNT assembled disposable paper SERS substrate was prepared by an electrostatic self-assembly method to detect chlorpyrifos residues in fruits., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A sepiolite/chitosan/silver nanoparticles (Sep/CTs/AgNPs) membrane substrate has been developed for the fast separation, enrichment, and surface-enhanced Raman scattering (SERS) determination of sulfamethoxazole all-in-one. The Sep/CTs/AgNPs membrane substrate possessed the ability of rapid separation and enrichment to simplify the process for pretreatment and improve the efficiency of analysis. The grown AgNPs can provide abundant hot spots and plasmonic areas to amplify the Raman signals of target molecules effectively. The membrane substrate exhibited good stability with relative standard deviations of 5.8% and 7.1% to same batch and different batches membrane substrate, respectively,  by detecting sulfamethoxazole. The SERS method based on Sep/CTs/AgNPs membrane substrate was used for the determination of sulfamethoxazole with a linear range of 0.05-2.0 mg/L, and the limit of detection was 0.020 mg/L. The established SERS method was finally applied to the quantification of sulfamethoxazole in animal-derived food samples. Sulfamethoxazole was actually found in crucian sample with 12.4 μg/kg, and the result was confirmed by a high-performance liquid chromatography method with relative error of 5.3%. The whole process of analysis can be finished within 25 min with recoveries of 89.3-102.2%. The SERS method based on Sep/CTs/AgNPs membrane substrate provided an integrated strategy for rapid and accurate SERS analysis in food safety issues., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An ultrasensitive fluorescence assay strategy on the basis of carbon dots (CDs) and cDNA-modified gold nanoparticles (AuNP-cDNA) was developed for the determination of microRNA-21 (miRNA-21) via internal filtering effect (IFE). Positively charged CDs (PEI-CDs), the fluorophores in IFE, were synthesized via a hydrothermal method using polyethyleneimine (PEI) as surface ligand. The maximum emission wavelength is located at 500 nm under the excitation of 410 nm. AuNPs, the absorbers, were modified with single-stranded DNA (cDNA), which is completely complementary to miRNA-21. The fluorescence of PEI-CDs is quenched due to the assembly of PEI-CDs and AuNPs-cDNA. In the presence of miRNA-21, the hybridization between miRNA-21 and cDNA causes the release of PEI-CDs and the recovery of fluorescence intensity.The fluorescence recovery degree is linearly correlated with the logarithm of miRNA-21 concentration in the range of 1-1000 fM. This method can be applied to determine miRNA-21 in real serum samples, and the detection results are in well agreement with those of qRT-PCR. The determination of miRNA-21 spiked into diluted human serum samples displays satisfactory recovery within the range 88.44-112.7%, which confirmed the reliability for miRNAs detection in real samples., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Chemical sensing for the sensitive and reliable detection of mercury(II) ions (Hg 2+ ) is of great importance in environmental protection, food safety, and biomedical applications. Due to the bio-enrichment property of Hg 2+ in organisms, it is particularly meaningful to develop an effective tool that can in situ and rapidly monitor the level of Hg 2+ in living organisms. In this work, we report ligand functionalized gold-silver bimetallic nanoclusters with bright red fluorescence as intracellular probes for imaging Hg 2+ in living cells and zebrafish. The bimetallic nanoclusters of DTT-GSH@Au/AgNCs (DG-Au/AgNCs) with strong fluorescence that benefited from the synergistic effect of Au and Ag atoms were obtained through a one-pot synthesis method, incorporating glutathione (GSH) and dithiothreitol (DTT) as the reducers and functionalized ligands. Attractively, the bright red fluorescence of DG-Au/AgNCs could be rapidly and selectively quenched by Hg 2+ within 1 min with a very low detection limit of 1.01 nM. Additionally, DG-Au/AgNCs had a great advantage in the detection of Hg 2+ in living cells and zebrafish owing to its notably strong red fluorescence at 665 nm, which could avoid effectively auto-fluorescence interference from the organism. Such easily prepared bimetallic fluorescent nanoclusters would be expected to provide a noninvasive and sensitive approach in the detection of heavy metals in situ for environmental protection., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

The development of the first microfluidic paper-based analytical device (µPAD) for the speciation of inorganic arsenic in environmental aqueous samples as arsenite (As(III)) and arsenate (As(V)) which implements hydride generation on a paper platform is described. The newly developed µPAD has a 3D configuration and uses Au(III) chloride as the detection reagent. Sodium borohydride is used to generate arsine in the device's sample zone by reducing As(III) in the presence of hydrochloric acid or both As(III) and As(V) (total inorganic As) in the presence of sulfuric acid. Arsine then diffuses across a hydrophobic porous polytetrafluoroethylene membrane into the device's detection zone where it reduces Au(III) to Au nanoparticles. This results in a color change which can be related to the concentration of As(III) or total inorganic As (i.e., As(III) and As(V)) concentration. Under optimal conditions, the µPAD is characterized by a limit of detection of 0.43 mg L -1 for total inorganic As (As(III) + As(V)) and 0.41 mg L -1 for As(III) and a linear calibration range in both cases of 1.2-8.0 mg As L -1 . The newly developed µPAD-based method was validated by applying it to groundwater and freshwater samples and comparing the results with those obtained by conventional atomic spectrometric techniques., (© 2022. The Author(s).)

A novel Apt-LFA has been established for kanamycin based on non-thiolated nucleic acid-modified colloidal gold nanoprobe (AuNPs@polyA-DNA). The improvement in nucleic acid hybridization speed and efficiency was verified by modifying AuNPs with polyA-DNA strands instead of thiolated oligonucleotides (SH-DNA) strands. Moreover, the AuNPs@polyA-DNA was explored to apply in an Apt-LFA. The experimental factors including the concentration of the aptamer, the concentration of SA-DNA T conjugate, the incubation time, and temperature were carefully investigated. In addition, the kanamycin aptamer was modified by extending several bases at its end to modulate the hybridization complementary strand, which was found to significantly improve the performance of Apt-LFA. Under optimal experimental conditions, the Apt-LFA can detect kanamycin in honey with a LOD of 250 ng mL -1 by the naked eyes. A linear range of 50-1250 ng mL -1 was obtained with a LOD of 15 ng mL -1 in honey by a portable reader. The Apt-LFA was successfully applied to the detection of kanamycin in honey with recoveries of 95.1-105.2%., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A label-free immunosensor was constructed in oxidation and reduction dual channel mode for the trace detection of cancer antigen 125 (CA125) in serum. The gold-vertical graphene/titanium dioxide (Au-VG/TiO 2 ) electrode was used as the signal-amplification platform, and cytosine and dopamine were used as probes in the oxidation and reduction channels, respectively. VG nanosheets were synthesized on a TiO 2 nanotube array via chemical vapor deposition (CVD), and Au nanoparticles were deeply embedded on the surface and in the root of the VG nanosheets via electrodeposition. The CA125 antibody was then directly immobilized onto the electrode surface, benefitting from its natural affinity for Au nanoparticles. In the oxidation and reduction channels the CA125 antibody-Au-VG/TiO 2 immune electrode had the same response concentration range (0.01-1000 mU∙mL -1 ) for the determination of the CA125 antigen. However, the oxidation channel had a higher sensitivity (14.82 μA•(log(mU•mL -1 )) -1 at a working potential of ~ 1.25 V vs. SCE), lower detection limit (0.0001 mU∙mL -1 ), higher stability, and lower performance deviation than the reduction channel. This immunosensor was successfully used for CA125 detection in human serum. The recoveries of spiked serum samples ranged from 99.8 ± 0.5 to 100 ± 0.4%. The study on the difference in the sensing performance between oxidation and reduction channels provides a preliminary experimental reference for exploring dual-channel synchronous detection immunosensors and verifying the accuracy of the assay based on dual-channel data, which will promote the development of reliable electrochemical immunosensor technology., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

By utilizing a target biorecognition reaction to induce the self-assembly of G-quadruplexes and the aggregation of gold nanoparticles (Au NPs), this work develops a novel colorimetric biosensing method for kanamycin (Kana) antibiotic detection. The compact G-quadruplex structure was assembled from its two half-split sequences which were designed in two hairpin substrates of the Mg 2+ -dependent DNAzyme (MNAzyme). Besides hybridizing with the aptamer strand, the MNAzyme sequence was also split into two half fragments to be designed in the two substrates. Upon the aptamer-recognition reaction toward Kana, the MNAzyme strand could be quantitatively released to cause the exposure of the split G-quadruplex-sequences on two hairpin substrate-modified Au NPs and simultaneous release of two half fragments of the MNAzyme-sequence. Thus, the K + -assisted self-folding of G-quadruplexes causes the cross-linking of the two Au NPs to realize the Au NP aggregation-based colorimetric signal output (measured at the largest absorption peak near 520 nm). Meanwhile, the self-assembled formation of the second MNAzyme drastically amplified the signal response. Under the optimal conditions, a wide linear range from 0.1 pg mL -1  to 10 ng mL -1 and an ultrahigh sensitivity with the detection limit of 76 fg mL -1 were obtained. The dose-recovery experiments in real samples showed satisfactory results with recoveries from 98.4 to 105.4% and relative errors compared with the ELISA method less than 4.1%. Due to the high selectivity, excellent repeatability and stability, and simple manipulation, this method indicates a promising potential for practical applications. A novel homogeneous biosensing method was developed for the convenient detection of the kanamycin antibiotic. The target biorecognition-induced and dual DNAzyme-catalytic assembly of G-quadruplexes enabled the amplified aggregation of gold nanoparticles for the simple, cheap, stable, and ultrasensitive colorimetric signal transduction of the method., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The rapid detection of biomolecules in a point of care (POC) setting is very important for diagnostic purposes. A platform which can provide this, whilst still being low cost and simple to use, is paper-based lateral flow immunoassays (LFIA). LFIA combine immunology and chromatography to detect a target by forming an immunocomplex with a label which traps them in a test zone. Qualitative analysis can be performed using the naked eye whilst quantitative analysis takes place by measuring the optical signal provided by the label at the test zone. There are numerous detection methods available; however, many suffer from low sensitivity and lack of multiplexing capabilities or are poor at providing POC quantitative analysis. An attractive method to overcome this is to use nanoparticles coated in Raman reporters as the labelled species and to analyse test zones using surface-enhanced Raman scattering (SERS). Due to the wide variety of metal nanoparticles, Raman reporter and laser excitations that are available, SERS-based LFIA have been adapted to identify and quantify multiple targets at once. Large Raman microscopes combined with long mapping times have limited the platform to the lab; however, by transferring the analysis to portable Raman instruments, rapid and quantitative measurements can be taken at the POC without any loss in sensitivity. Portable or handheld SERS-LFIA platforms can therefore be used anywhere, from modern clinics to remote and resource-poor settings. This review will present an overview of SERS-based LFIA platforms and the major recent advancements in multiplexing and portable and handheld detection with an outlook on the future of the platform., (© 2022. The Author(s).)

The surface-enhanced Raman scattering (SERS) technique has displayed a broad application prospect in disease diagnosis owing to its high sensitivity, fast responsiveness, and high specificity. In this study, we developed a SERS-based immunoassay for the detection of cryptococcal capsular polysaccharide (glucuronoxylomannan, GXM), which is an important biomarker of cryptococcosis. The coupled localized surface plasmon resonance effect between magnetic SERS substrates and SERS tags gave rise to an enhanced Raman signal upon the formation of sandwich complexes, which contributes to the sensitive and specific detection of GXM. As a result, the developed method provided a lower limit of detection (1.25 ng/mL) than conventional methods, such as latex agglutination, lateral flow assay, and enzyme-linked immunosorbent assay. Additionally, a recovery experiment was performed to detect GXM in human serum, which also validated the potential advantages of a SERS-based immunoassay in the clinical diagnosis of cryptococcosis., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)