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Flexible thermoelectric (TE) generators have received great attention as a sustainable and reliable option to convert heat from the human body and other ambient sources into electricity. This study provides a synthesis route that involves thermally induced diffusion to introduce Te and Se into Bi, fabricating an n-type Bi-Te-Se flexible thin film on a flexible substrate. This specific synthesis alters the crystal orientation (00 l ) of the thin film, improving in-plane electrical transportation and optimizing carrier concentration. Consequently, Bi x Te y Se 0.42 enhanced both the Seebeck coefficient and electrical conductivity, achieving a power factor of 17.1 μW cm -1 K -2 at room temperature. The TE device assembled with p-type Sb 2 Te 3 exhibited exceptional flexibility with only a 26.2% change in resistance after 1000 times of bending at a radius of about 6 mm. The resistance change was further reduced to 7.5% after the application of a vinyl laurate coating. The fabricated TE device generated an ultrahigh output power of 792 nW with a temperature difference of 30 K.

After entering host cells by endocytosis, influenza A virus (IAV) is transported along microfilaments and then transported by dynein along microtubules (MTs) to the perinuclear region for genome release. Understanding the mechanisms of dynein-driven transport is significant for a comprehensive understanding of IAV infection. In this work, the roles of dynactin in dynein-driven transport of IAV were quantitatively dissected in situ using quantum dot-based single-virus tracking. It was revealed that dynactin was essential for dynein to transport IAV toward the nucleus. After virus entry, virus-carrying vesicles bound to dynein and dynactin before being delivered to MTs. The attachment of dynein to the vesicles was dependent on dynactin and its subunits, p150 Glued and Arp1. Once viruses reached MTs, dynactin-assisted dynein initiates retrograde transport of IAV. Importantly, the retrograde transport of viruses could be initiated at both plus ends (32%) and other regions on MTs (68%). Subsequently, dynactin accompanied and assisted dynein to persistently transport the virus along MTs in the retrograde direction. This study revealed the dynactin-dependent dynein-driven transport process of IAV, enhancing our understanding of IAV infection and providing important insights into the cell's endocytic transport mechanism.

Influenza A virus (IAV) can cause infectious respiratory diseases in humans and animals. IAVs mutate rapidly through antigenic drift and shift, resulting in the emergence of numerous IAV subtypes and significant challenges for IAV detection. Therefore, achieving the simultaneous detection of multiple IAVs is crucial. In this work, three specific aptamers targeting the hemagglutination (HA) protein of the influenza A H5N1, H7N9, and H9N2 viruses were screened using a multichannel magnetic microfluidic chip. The aptamers exhibit nanomolar affinity and excellent specificity for the HA protein of H5N1, H7N9, and H9N2 viruses. Furthermore, three specific aptamers were truncated and labeled with different fluorescence markers to realize fluorescence quantitative detection of influenza A H5N1, H7N9, and H9N2 viruses through an aptamer sandwich assay in 1 h. The limit of detection (LOD) of the developed method is 0.38 TCID 50 /mL for the H5N1 virus, 0.75 TCID 50 /mL for the H7N9 virus, and 1.14 TCID 50 /mL for the H9N2 virus. The detection method has excellent specificity, strong anti-interference ability, and good reproducibility. This work provides a sensitive quantitative detection method for the H5N1, H7N9, and H9N2 viruses, enabling quantitative fluorescence detection for multiple IAV subtypes.

In recent years, silver nanoparticles (Ag NPs) have been used as positive electrode material for zinc/silver batteries, and the silver oxides formed during the charging process determine the discharge performance of batteries. Therefore, it is important to study the oxidation behavior of Ag NPs in alkaline solution. Single-nanoparticle collision is an important tool for analyzing oxidation behavior of individual nanoparticles. Based on thermodynamic information from collision events, it is known that oxidation products are potential-dependent and size-dependent. Based on dynamic information, including collisional peak shapes and duration time, it was observed that the Ag NP collision oxidation process changed from stepwise oxidation to direct oxidation as the potential increased or size decreased. This work provides guidance for application of Ag NPs in zinc/silver batteries and proposed a strategy for oxidation behavior of individual NP that could be tracked in situ through an all-encompassing view of thermodynamic and dynamic information.

Single particle collision is an important tool for size analysis at the individual particle level; however, due to complex dynamic behaviors of nanoparticles on the surface of an electrode, the accuracy of size discrimination is limited. A silver (Ag) nanoparticle (NP) was chosen as the research target, and the dynamic behavior of Ag NPs was simplified by enhancing adsorption between Ag NP and Au ultramicroelectrode (UME) in alkaline media. Immediately after, accurate dynamic and thermodynamic information on single Ag NP was accurately extracted from collision events, including current intensity, transferred charge, and duration time. On the basis that there were differences between parameters of different-sized Ag NPs, multiparameter size discrimination was proposed, which improved the accuracy compared to single-parameter discrimination. More intriguingly, multiparameter analysis was combined with artificial intelligence, a tool adept at processing multidimensional data, for the first time. Finally, artificial intelligence-assisted multiparameter size discrimination was successfully used to intelligently distinguish mixed Ag NPs, with an optimal accuracy of more than 95%. To sum up, the artificial intelligence-assisted multiparameter method showed an excellent ability to quickly achieve the most accurate size discrimination of nanoparticles at the level of individual particle and provide an effective guidance for the application of nanoparticles.

Recently, perovskite solar cells (PSCs) based on quasi-two-dimensional (quasi-2D) perovskites have drawn more attention due to their excellent stability, although their efficiencies are still lower than those of 3D ones. Here we applied post-treatment of 2D perovskite GAMA 5 Pb 5 I 16 (GA = guanidinium, MA = methylammonium) films with acetaminophen (AMP) to improve their performance. The efficiency of the solar cells with 2 mg/mL AMP post-treatment increased to 18.01% from 16.72% for those without post-treatment. The efficiency improvement results from the enlarged grain size, reduced trap state density, and better energy level matching after AMP post-treatment. In addition, the stability of the solar cells is improved. The solar cells with AMP post-treatment maintain 91% of the original power conversion efficiency value after aging for 30 days in the atmosphere. This work opens a new approach for the efficiency and stability enhancement of quasi-2D PSCs.

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1 + sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivo detection of PD-L1 + sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivo detection of PD-L1 + sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1 + sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1 + sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1 + sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivo detection of PD-L1 + sEVs, contributing to the clinical diagnosis and treatment of tumor.

It is crucial to develop universal inhibitors for viral inhibition due to the rapid mutation of viruses. Herein, a universal aptamer inhibitor was developed that enabled a single DNA molecule to recognize several hemeagglutinin (HA) protein subtypes, inducing broad neutralization against influenza A viruses (IAVs). Through a multi-channel enrichment (MCE) strategy, a high-affinity aptamer named UHA-2 was obtained, with its dissociation constants ( K d ) for three different HA proteins being 1.5 ± 0.2 nM (H5N1), 3.7 ± 0.4 nM (H7N9), and 10.1 ± 1.1 nM (H9N2). The UHA-2 aptamer had a universal inhibition effect, by which it could broadly neutralize influenza A H5N1, H7N9, H9N2, H1N1, and H3N2 viruses. Universal aptamer inhibitors have the advantages of acquisition in vitro , stability, simple structure, small size, etc. This study not only develops a novel universal aptamer to achieve a broad inhibition effect on various IAVs, but also opens up an efficient strategy for the development of universal inhibitors against viruses., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Poor stability retards the industrialization of perovskite solar cells (PSCs). One of the effective ways to solve this issue is to modify the perovskite surface to improve the efficiency and stability of the PSCs. Herein, we synthesized CuFeS 2 nanocrystals and applied them to modify the perovskite surface. The efficiency of the PSCs with CuFeS 2 modification is improved to 20.17% from 18.64% for the control devices. Some investigations demonstrate that the CuFeS 2 modification passivates the perovskite surface defects and induces better energy band arrangement. Furthermore, the stability of the PSCs with CuFeS 2 modification is improved compared with the devices without CuFeS 2 modification. The efficiency of the PSCs with CuFeS 2 modification maintains 93% of its initial value, whereas that of the devices without CuFeS 2 modification decreases to 61% of the initial value. This work demonstrates that CuFeS 2 is a novel material used as a modification layer to enhance the efficiency and stability of the PSCs.

Liquid biopsy technology involves taking samples from body fluids in a minimally invasive way and analyzing tumor markers to achieve early diagnosis and efficacy evaluation of tumors. The development of real-time cancer diagnosis and treatment strategies based on liquid biopsy technology is of great significance to cancer management. This paper described an extracorporeal circulation based on a three-dimensional (3D) magnetic chip (3DMC-system) for in vivo detection and real-time monitoring of circulating tumor cells (CTCs). Utilizing biofunctionalized magnetic nanospheres (MNs) with CTC recognition function, this 3DMC-system could effectively achieve the real-time monitoring of CTCs in vivo with good stability and strong anti-interference. Compared with in vitro CTC detection, in vivo detection could not only detect more CTCs but also detect the presence of CTCs in the blood at an early stage of the tumor, when tumor metastasis is not observed in imaging. In addition, due to the flexibility of the chip design, the system can easily add a treatment module to integrate cancer diagnosis and treatment together. With good biocompatibility and high stability, this 3DMC-system is expected to provide a new personalized medical program for cancer patients.

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V + EGFR + EVs and Annexin V - EGFR + EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR + EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V + EGFR + EVs to Annexin V - EGFR + EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Hippophae rhamnoides L. (sea buckthorn), consumed as a food and health supplement worldwide, has rich nutritional and medicinal properties. Different parts of H. rhamnoides L. were used in traditional Chinese medicines for relieving cough, aiding digestion, invigorating blood circulation, and alleviating pain since ancient times. Phytochemical studies revealed a wide variety of phytonutrients, including nutritional components (proteins, minerals, vitamins, etc.) and functional components like flavonoids ( 1 - 99 ), lignans ( 100 - 143 ), volatile oils ( 144 - 207 ), tannins ( 208 - 230 ), terpenoids ( 231 - 260 ), steroids ( 261 - 270 ), organic acids ( 271 - 297 ), and alkaloids ( 298 - 305 ). The pharmacological studies revealed that some crude extracts or compounds of H. rhamnoides L. demonstrated various health benefits, such as anti-inflammatory, antioxidant, hepatoprotective, anticardiovascular disease, anticancer, hypoglycemic, hypolipidemic, neuroprotective, antibacterial activities, and their effective doses and experimental models were summarized and analyzed in this paper. The quality markers (Q-markers) of H. rhamnoides L. were predicted and analyzed based on protobotanical phylogeny, traditional medicinal properties, expanded efficacy, pharmacokinetics and metabolism, and component testability. The applications of H. rhamnoides L. in juice, wine, oil, ferment, and yogurt were also summarized and future prospects were examined in this review. However, the mechanism and structure-activity relationship of some active compounds are not clear, and quality control and potential toxicity are worth further study in the future.

In situ monitoring of the agglomeration/aggregation process of nanoparticles (NPs) is crucial because it seriously affects cell entry, biosafety, catalytic performance of NPs, and so on. Nevertheless, it remains hard to monitor the solution phase agglomeration/aggregation of NPs via conventional techniques such as electron microscopy, which requires sample pretreatment and cannot represent native state NPs in solution. Considering that single-nanoparticle electrochemical collision (SNEC) is powerful to detect NPs in solution at the single-particle level, and the current lifetime, which refers to the time that current intensity decays to 1/e of the original value, is skilled in distinguishing different sized NPs, herein, a current lifetime-based SNEC has been developed to distinguish a single Au NP ( d = 18 nm) from its agglomeration/aggregation. Based on this, the agglomeration/aggregation process of small-sized NPs and the discrimination of agglomeration vs aggregation have been carefully investigated at the single-particle level. Results showed that the agglomeration/aggregation of Au NPs ( d = 18 nm) in 0.8 mM HClO 4 climbed from 19% to 69% over two hours, whereas there was no visible granular sediment, and Au NPs tended to agglomerate rather than aggregate irreversibly under normal conditions. Hence, the proposed current lifetime-based SNEC could serve as a complementary method to in situ monitor the agglomeration/aggregation of small-sized NPs in solution at the single-particle level and provide effective guidance for the practical application of NPs.

Recent advances of photonic crystals are driven to mechanical sensors and smart wearable devices; however, for chiral photonic cellulose nanocrystal (CNC) materials, vivid structural coloration and reversible mechanochromism like chameleon skin remain a big challenge. Here, we report a ternary co-assembly and post-UV-irradiation polymerization strategy to develop flexible and elastic CNC composite films, which, notably, have naked-eye-visible brilliant structural colors and stretching-induced color change covering a broad wavelength region at a moderate deformation (like skin). By adjusting the stretching, the film is designed as a smart skin to adapt to surrounding environments for camouflage. This work offers a universal strategy for constructing biomimic optically functional cellulose skins.

Single-nanoparticle collision electrochemistry (SNCE) has gradually become an attractive analytical method due to its advantages in analytical detection, such as a fast response, low cost, low sample consumption, and in situ real-time detection of analytes. However, the biological analyte's direct detection based on the SNCE blocking mode has the problems of low sensitivity and specificity. In this work, an SNCE biosensor based on SNCE electrocatalytic strategy was used for the detection of H7N9 AIV. Nucleic acid aptamers were introduced to recognize the target virus (H7N9 AIV). After the recognition event, ssDNA 1 was released and hybridized with another ssDNA 2 . Owing to the nicking endonuclease Nt.AlwI-mediated target nucleic acid cyclic amplification, one virus particle can indirectly induce the release of 4.2 × 10 6 Au NPs that can be counted by the SNCE electrocatalytic strategy. The high conversion efficiency greatly improved the detection sensitivity, and the detection limit was as low as 24.3 fg/mL. Therefore, the constructed biosensor can achieve a highly sensitive and specific detection of H7N9 AIV and show a great potential in bioanalytical application.

Magnetic resonance imaging (MRI) has excellent potential in the clinical monitoring of tumors because it can provide high-resolution soft tissue imaging. However, commercial contrast agents (CAs) used in MRI still have some problems such as potential toxicity to the human body, low relaxivity, and a short MRI acquisition window. In this study, ultrasmall MnSe nanoparticles are synthesized by living Staphylococcus aureus cells. The as-prepared MnSe nanoparticles are monodispersed with a uniform particle size (3.50 ± 0.52 nm). Due to the ultrasmall particle size and good water solubility, the MnSe nanoparticles exhibit in vitro high longitudinal relaxivity properties (14.12 ± 1.85 mM -1 ·s -1 ). The CCK-8 colorimetric assay, histological analysis, and body weight results show that the MnSe nanoparticles do not have appreciable toxicity on cells and organisms. Besides, the MnSe nanoparticles as T 1 -MRI CAs offer a long MRI acquisition window to tumor imaging (∼7 h). This work provides a promising T 1 -MRI CA for clinical tumor imaging and a good reference for the application of functional MnSe nanoparticles in the biomedicine field.

Accurate size analysis of nanoparticles (NPs) is vital for nanotechnology. However, this cannot be realized based on conventional single-nanoparticle collision (SNC) because the current intensity, a thermodynamic parameter of SNC for sizing NPs, is always smaller than the theoretical value due to the effect of NP movements on the electrode surface. Herein, a size-dependent dynamic parameter of SNC, current lifetime, which refers to the time that the current intensity decays to 1/e of the original value, was originally utilized to distinguish differently sized NPs. Results showed that the current lifetime increased with NP size. After taking the current lifetime into account rather than the current intensity, the overlap rates for the peak-type current transients of differently sized Pt NPs (10 and 15 nm) and Au NPs (18 and 35 nm) reduced from 73 and 7% to 45 and 0%, respectively, which were closer to the theoretical values (29 and 0%). Hence, the proposed SNC dynamics-based method holds great potential for developing reliable electrochemical approaches to evaluate NP sizes accurately.

Limited to the accuracy of size resolution, single entity collision biosensing (SECBS) for multiplex immunoassays remains challenging, because it is difficult to get the true value of nanoparticle (NP) sizes based on the current intensity due to the complex movement of NPs on the electrode surface. Considering that the size-dependent movement of NPs meanwhile will generate a characteristic current shape, in this work, the huge difference in the current rise time of 5 and 15 nm Pt NPs colliding on an Au ultramicroelectrode ( d = 30 μm) was originally used to develop a size-resolved SECBS for multiplex immunoassays of miRNAs. The limit concentration that can be detected was 0.5 fM. Compared with conventional electrochemical biosensors for multiplex immunoassays, for the size-resolved SECBS, one does not need to worry about potential overlapping. Therefore, the proposed method demonstrates a promising potential for the application of SECBS in multiplex immunoassays.

An ultrasensitive electrochemiluminescence (ECL) biosensor was proposed based on a closed bipolar electrode (BPE) for the detection of alkaline phosphatase (ALP). For most of the BPE-ECL biosensors, an effective signal amplification strategy was the key to enhance the sensitivity of the system. Herein, the signal amplification strategy of the enzyme catalysis was utilized in the BPE-ECL system. Au nanoparticles (NPs) were electrodeposited on the cathode surface of the ITO electrode to improve the stability and sensitivity of the signal. Compared with the previous BPE-ECL biosensors, the sensitivity was increased by at least 3 orders of magnitude. The biosensor showed high sensitivity and specificity of ALP detection with a detection limit of as low as 3.7 aM. Besides, it was further applied to the detection of ALP in different types of cells and successfully realized ALP detection in single Hep G2 cell, which had a huge application prospect in single biomolecule detection or single cell analysis.

Due to spontaneous organization of cellulose nanocrystals (CNCs) into the chiral nematic structure that can selectively reflect circularly polarized light within a visible-light region, fabricating stretching deformation-responsive CNC materials is of great interest but is still a big challenge, despite such a function widely observed from existing creatures, like a chameleon, because of the inherent brittleness. Here, a flexible network structure is introduced in CNCs, exerting a bridge effect for the rigid nanomaterials. The as-prepared films display high flexibility with a fracture strain of up to 39%. Notably, stretching-induced structural color changes visible to the naked eye are realized, for the first time, for CNC materials. In addition, the soft materials show humidity- and compression-responsive properties in terms of changing apparent structural colors. Colored marks left by ink-free writing can be shown or hidden by controlling the environmental humidities. This biobased photonic film, acting as a new "smart skin", is potentially used with multifunctions of chromogenic sensing, encryption, and anti-counterfeit.

DNA damage response (DDR) pathways are crucial for the survival of cancer cells and are attractive targets for cancer therapy. Bloom syndrome protein (BLM) is a DNA helicase that performs important roles in DDR pathways. Our previous study discovered an effective new BLM inhibitor with a quinazolinone scaffold by a screening assay. Herein, to better understand the structure-activity relationship (SAR) and biological roles of the BLM inhibitor, a series of new derivatives were designed, synthesized, and evaluated based on this scaffold. Among them, compound 9h exhibited nanomolar inhibitory activity and binding affinity for BLM. 9h could effectively disrupt BLM recruitment to DNA in cells. Furthermore, 9h inhibited the proliferation of the colorectal cell line HCT116 by significantly triggering DNA damage in the telomere region and inducing apoptosis, especially in combination with a poly (ADP-ribose) polymerase (PARP) inhibitor. This result suggested a synthetic lethal effect between the BLM and PARP inhibitors in DDR pathways.

Near-infrared (NIR) fluorescence has attracted much attention in biomedical fields because it offers deep tissue penetration and high spatial resolution. Herein, a method is developed for the preparation of NIR fluorescent nanocomposites (NCs) by encapsulating natural chlorophyll (Chl) into the micelles of octylamine-modified poly(acrylic acid) (OPA). Both femtosecond transient absorption spectra and isothermal titration calorimetry thermogram reveal that the micelles of OPA provide a hydrophobic environment for the improved fluorescence efficiency. Hence the resulted Chl NCs possess unique properties such as ultrasmall size, outstanding photostability, good biocompatibility, and superbright NIR fluorescence emission. In vivo imaging of sentinel lymph node is achieved in nude mice, demonstrating the potential of Chl NCs in biomedical applications. This work provides a new strategy for the preparation of highly biocompatible NIR fluorescence labeling nanocomposites., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

To enhance signal acquisition stability and diminish background interference for conventional flow bead-based fluorescence detection methods, we demonstrate here an exceptional microfluidic chip assisted platform by integrating near-infrared optical tweezers with upconversion luminescence encoding. For the former, a single 980 nm laser is employed to perform optical trapping and concurrently excite upconversion luminescence, avoiding the fluctuation of the signals and the complexity of the apparatus. By virtue of the favorable optical properties of upconversion nanoparticles (UCNPs), the latter is carried out by employing two-color UCNPs (Er-UCNPs and Tm-UCNPs) with negligible spectral overlaps. With the assistance of the double key techniques, we fabricated complex microbeads referred to a UCNPs-miRNAs-microbead sandwich construct by a one-step nucleic acid hybridization process and then obtained uniform terrace peaks for the automatic and simultaneous quantitative determination of miRNA-205 and miRNA-21 sequences with a detection limit of pM level on the basis of a special home-built flow bead platform. Furthermore, the technique was successfully applied for analyzing complex biological samples such as cell lysates and human tissue lysates, holding certain potential for disease diagnosis. In addition, it is expected that the flow platform can be utilized to investigate many other biomolecules of single cells and to allow analysis of particle heterogeneity in biological fluid by means of optical tweezers.

In the present study, we aimed to characterize gut microbiome and develop a gut microbiome-based diagnostic model in patients with coronary artery disease (CAD). Prospectively, we collected 309 fecal samples from Central China and Northwest China and carried out the sequencing of the V3-V4 regions of the 16S rRNA gene. The gut microbiome was characterized, and microbial biomarkers were identified in 152 CAD patients and 105 healthy controls (Xinjiang cohort, n = 257). Using the biomarkers, we constructed a diagnostic model and validated it externally in 34 CAD patients and 18 healthy controls (Zhengzhou cohort, n = 52). Fecal microbial diversity was increased in CAD patients compared to that in healthy controls ( P = 0.021). Phylum Bacteroidetes was increased in CAD patients versus healthy controls ( P = 0.001). Correspondingly, 48 microbial markers were identified through a 10-fold cross-validation on a random forest model, and an area under the curve (AUC) of 87.7% (95% CI: 0.832 to 0.916, P < 0.001) was achieved in the Xinjiang cohort (development cohort, n = 257). Notably, an AUC of 90.4% (95% CI: 0.848 to 0.928, P < 0.001) was achieved using combined analysis of gut microbial markers and clinical variables. This model provided a robust tool for the prediction of CAD. It could be widely employed to complement the clinical assessment and prevention of CAD.

Single-entity electrochemistry (SEEC), a promising method for biosensing, has an intrinsic limitation on sensitivity since at most one colliding entity can be successfully triggered by one target. Here, we take advantage of one-to-many (1: n ) signal amplification to develop a new single-entity electrochemistry biosensing (SEECBS), integrating satellite magnetic nanoparticle (MN)-DNA-Pt nanoparticle (NP) conjugates, duplex-specific nuclease (DSN) assisted Pt NPs releasing with stabilization, and effective collision of small sized and nearly naked Pt NPs. Compared with conventional SEECBS, the 1: n SEECBS can successfully enrich ∼2 nM Pt NPs by adding 50 aM microRNA (miRNA), in other words, ∼4 × 10 7 Pt NPs can be triggered by one target. The proposed SEECBS allows the detection of 47 aM miRNA-21, nearly 6 orders of magnitude lower than the previous work, and discrimination of nontarget miRNAs containing even single-nucleotide mismatch. Besides, this method has also been successfully demonstrated for quantification of miRNA in different cell lines. Therefore, the proposed method holds great potential for the application of SEECBS in early diagnosis and prognosis monitoring of cancer.

The accurate and rapid monitoring of the expression levels of enterovirus 71 (EV71)-related microRNAs (miRNAs) can contribute to diagnosis of hand, foot, and mouth disease (HFMD) at the early stage. However, there is currently a lack of convenient methods for simultaneous monitoring of multiplex miRNAs in one step. Herein a one-step method for the simultaneous monitoring of multiple EV71 infection-related miRNAs is developed based on core-satellite structure assembled with magnetic nanobeads and quantum dots (MNs-ssDNA-QDs). In the presence of target miRNAs, duplex-specific nuclease (DSN)-assisted target recycling can be triggered, resulting in the release of QDs and recycling of target miRNAs. Then the simultaneous quantification can be easily realized by recording the corresponding amplified fluorescence signal of QDs in the suspension. With this method, simultaneous detection of hsa-miRNA-296-5p and hsa-miRNA-16-5p, potential biomarkers of EV71 infection, can be easily achieved with femtomolar sensitivity and single-base mismatch specificity. Moreover, the method is successfully used for monitoring of the expression level of miRNAs in EV71-infected cells at different time points, demonstrating the potential for diagnostic applications. With the merits of one-step operation and single-nucleotide mismatch discrimination, this work opens a new avenue for multiplex miRNAs detection. As different nucleotide sequences and multicolor QDs can be employed, this work is expected to offer great potential for the development of high throughput diagnosis.

We demonstrate an effective approach to realize active and real-time temperature monitoring around the gold nanobipyramids (AuNBPs)-labeled cancer cell under 808 nm laser irradiation by combining optical tweezers and temperature-sensitive upconversion microparticles (UCMPs). On the one hand, the aptamer-modified AuNBPs that absorb laser at 808 nm not only act as an excellent photothermal reagent but also accurately and specifically bind the target cancer cells. On the other hand, the single optically trapped NaYF 4 :Yb 3+ , Er 3+ UCMPs with a 980 nm laser exhibit temperature-dependent luminescence properties, where the intensity ratio of emission 525 and 547 nm varies with the ambient temperature. Therefore, real-time temperature variation monitoring is performed by 3D manipulation of the trapped single UCMP to control its distance from the AuNBPs-labeled cancer cell while being photothermally killed. The results show distance-related thermal propagation because the temperature increase reaches as high as 10 °C at a distance of 5 μm from the cell, whereas the temperature difference drops rapidly to 5 °C when this distance increases to 15 μm. This approach shows that the photothermal conversion from AuNBPs is sufficient to kill the cancer cells, and the temperature increase can be controlled within the micrometer level at a certain period of time. Overall, we present a micrometer-size thermometer platform and provide an innovative strategy to measure temperature at the micrometer level during photothermal killing of cancer cells.

In vivo detection of circulating tumor cells (CTCs) which inspect all of the circulating blood in body seems to have more advantages on cell capture, especially in earlier cancer diagnosis. Herein, based on in vivo microfluidic chip detection system (IV-chip-system), an extracorporeal circulation was constructed to effectively detect and monitor CTCs in vivo. Combined with microfluidic chip and immunomagnetic nanosphere (IMN), this system not only acts as a window for CTC monitoring but also serves as a collector for further cancer diagnosis and research on CTCs. Compared with the current in vivo detection method, this system can capture and detect CTCs in the bloodstream without any pretreatments, and it also has a higher CTC capture efficiency. It is worth mentioning that this system is stable and biocompatible without any irreversible damage to living animals. Taking use of this system, the mimicked CTC cleanup process in the blood vessel is monitored, which may open new insights in cancer research and early cancer diagnosis.

Nanosized oncolytic viral light particles (L-particles), separated from progeny virions, are composed of envelopes and several tegument proteins of viruses, free of nucleocapsids. The noninfectious L-particles experience the same internalization process as mature oncolytic virions, which exhibits great potential to act as targeted therapeutic platforms. However, the clinical applications of L-particle-based theranostic platforms are rare due to the lack of effective methods to transform L-particles into nanovectors. Herein, a convenient and mild strategy has been developed to transform L-particles into near-infrared (NIR) fluorescence Ag 2 Se quantum dot (QD)-labeled active tumor-targeting nanovectors for real-time in situ imaging and drug delivery. Utilizing the electroporation technique, L-particles can be labeled with ultrasmall water-dispersible NIR fluorescence Ag 2 Se QDs with a labeling efficiency of ca . 85% and loaded with antitumor drug with a loading efficiency of ca . 87%. Meanwhile, by harnessing the infection mechanism of viruses, viral L-particles are able to recognize and enter tumor cells without further modification. In sum, a trackable and actively tumor-targeted theranostics nanovector can be obtained efficiently and simultaneously. Such multifunctional nanovectors transformed from viral L-particles have exhibited excellent properties of active tumor-targeting, in vivo tumor imaging, and antitumor efficacy, which opens a new window for the development of natural therapeutic nanoplatforms.

The functional groups and π-electron system of carbon dots (C-dots) were carefully controlled by several innovative chemical methods, without any changes in size, to unravel the relationship between the surface structure and photoluminescence (PL). The results of experiments and theoretical calculations reveal that the PL of C-dots is related to the surface state. The energy gap is determined by the coupling of the π-electron system and carbonyl group, and the quantum yield (QY) is dependent on the carbonyl group. The carbonyl group is the main factor increasing the ratio of nonradiation to radiation recombination, thereby leading to the low QY of C-dots. This work provides a strategy for effectively tuning the structure of C-dots, giving rise to the tunable PL emission wavelength and highly desirable QY, which enables us to further unravel the PL mechanism.

The rapid and sensitive detection of pathogens is extremely crucial for timely clinical diagnosis and diseases control. Here, by employing cellular beacons with in situ synthesized QDs created from Staphylococcus aureus ( S. aureus), we efficiently fabricated an antibody (Ab) and acetylcholinesterase (AChE)-functionalized nanobioprobe, i.e., multifunctional cellular beacons (MCBs), avoiding complicated modification. Coupled with magnetic separation, a novel method for pathogen detection with the naked eye is established. With this method, enterovirus 71 (EV71) can be detected by the naked eye through the aggregation of gold nanoparticles that is triggered by the product of AChE catalyzed acetylthiocholine, with a detection limit of 0.5 ng/mL. Moreover, due to the MCBs have high luminance with perfect uniformity, the detection can also be realized by counting the number of MCBs, with a detection limit of 1 ng/mL. The method is validated with human throat swabs, resulting in a complete consistence with reverse transcription-polymerase chain reaction results. This study reports the first cellular beacons-based method for pathogen detection by the naked eye and broadens the applicability of cell self-synthesized nanoparticles-based immunoassays. Moreover, the MCBs-based method will provide a powerful tool for clinical detection.

Different kinds of artificial drug delivery systems (DDS) have been widely exploited and utilized toward effective tumor therapy. Establishing a biocompatible DDS with a flexible release of the therapeutic agents has been a challenges and an impetus to the development of tumor diagnosis and therapy fields. Herein, the chemotherapeutic agents doxorubicin hydrochloride (DOX) and photosensitizer indocyanine green (ICG) were simultaneously packaged into the cavity of microvesicles (MVs) through the electroporation technique. With the aid of MVs-based DDS, the packaged therapeutic agents could be effectively delivered into the target tumor cells. The ambient temperature sharply increased because of controllable external near-infrared (NIR) laser irradiation, which induced the cracking of MVs-based DDS, directly accompanied by the dynamic and controllable release of DOX and ICG. Almost all the tumor cells could be killed by the synergistic effect of the released DOX and ICG. This research successfully established a smart DDS with NIR laser inducing controllable release of therapeutic agents for effective synergistic photochemotherapy toward cervical cancer.

Homologous recombination repair (HRR), a crucial approach in DNA damage repair, is an attractive target in cancer therapy and drug design. The Bloom syndrome protein (BLM) is a 3'-5' DNA helicase that performs an important role in HRR regulation. However, limited studies about BLM inhibitors and their biological effects have been reported. Here, we identified a class of isaindigotone derivatives as novel BLM inhibitors by synthesis, screening, and evaluating. Among them, compound 29 was found as an effective BLM inhibitor with a high binding affinity and good inhibitory effect on BLM. Cellular evaluation indicated that 29 effectively disrupted the recruitment of BLM at DNA double-strand break sites, promoted an accumulation of RAD51, and regulated the HRR process. Meanwhile, 29 significantly induced DNA damage responses, as well as apoptosis and proliferation arrest in cancer cells. Our finding provides a potential anticancer strategy based on interfering with BLM via small molecules.

Aptamers for Ebola virus (EBOV) offer a powerful means for prevention and diagnostics. Unfortunately, few aptamers for EBOV have been discovered yet. Herein, assisted by magnetism-controlled selection chips to strictly manipulate selection conditions, a highly efficient aptamer selection platform for EBOV is proposed. With highly stringent selection conditions of rigorous washing, manipulation of minuscule amounts of magnetic beads, and real-time evaluation of the selection effectiveness, the selection performance of the platform was improved significantly. In only three rounds of selection, the high-performance aptamers for EBOV GP and NP proteins were obtained simultaneously, with dissociation constants ( K d ) in the nanomolar range. The aptamer was further applied to the detection of EBOV successfully, with a detection limit of 4.2 ng/mL. The whole detection process that consisted of sample mixing, separation, and signal acquisition was highly integrated and conducted in a magnetism-controlled detection chip, showing high biosafety and great potential for point-of-care detection. The method may open up new avenues for prevention and control of EBOV.

The fluorescence method has made great progress in the construction of sensitive sensors but the background fluorescence of the matrix and photobleaching limit its broad application in clinical diagnosis. Here, we propose a digital single virus immunoassay for multiplex virus detection by using fluorescent magnetic multifunctional nanospheres as both capture carriers and signal labels. The superparamagnetism and strong magnetic response ability of nanospheres can realize efficient capture and separation of targets without sample pretreatment. Due to their distinguishable fluorescence imaging and photostability, the nanospheres enable single-particle counting for ultrasensitive multiplexed detection. Furthermore, the integration of digital analysis provided a reliable quantitative strategy for the detection of rare targets. Based on multifunctional nanospheres and digital analysis, a digital single virus immunoassay was proposed for simultaneous detection of H9N2, H1N1, and H7N9 avian influenza virus without complex signal amplification, whose detection limits were 0.02 pg/mL. Owing to its good specificity and anti-interference ability, the method showed great potential in single biomolecules, multiplexed detection, and early diagnosis of diseases.

Rapid and sensitive foodborne pathogen detection assay, which can be applied in multiple fields, is essential to timely diagnosis. Herein, we proposed a multisignal readout lateral flow immunoassay for Salmonella typhimurium ( S. typhi) detection. The assay employs colorimetric-fluorescent-magnetic nanospheres (CFMNs) as labels, which possess multifunctional target separation and enrichment, multisignal readout, and two formats of quantitation. The assay for S. typhi detection involves magnetic separation and chromatography. First, the S. typhi were separated and enriched from matrix by antibody labeled CFMNs, and then the S. typhi-containing suspension is added onto the sample pad to flow up the test strip. The introduction of magnetic separation enhances anti-interference ability and 10-fold sensitivity, making the assay possible for practical application. The assay has realized naked eye detection of 1.88 × 10 4 CFU/mL S. typhi, and 3.75 × 10 3 CFU/mL S. typhi can be detected with a magnetic assay reader, which is 2-4 orders of magnitude lower than other label-based LFIAs, with a quantitation range of 1.88 × 10 4 to 1.88 × 10 7 CFU/mL by measuring the fluorescence intensity and magnetic signal. Moreover, the successful detection of S. typhi in complex matrix (tap water, milk, fetal bovine serum, and whole blood) indicated its potential application in real samples.

Influenza A virus (IAV), a risk to public health, is enveloped and contains viral ribonucleoprotein (vRNP) complexes, where vRNP complexes are central to every aspect of the IAV life cycle. Labeling both the vRNP complexes and viral envelope with quantum dots (QDs) is conducive to achieving global long-term tracking of a single IAV infecting host cell, which has potential to provide valuable information for revealing mechanisms of IAV infection. However, even though some strategies for labeling of the viral envelope with QDs have been developed, there are few strategies for coupling of QDs to the vRNP complexes inside IAV so far. Herein, we devised a convenient electroporation-based strategy, coupled with antibody binding, to transfer green QDs-labeled nucleoprotein antibodies (GQDs-NPAb) into H1N1 and achieved the labeling of vRNP complexes with QDs [H1N1(GQDs)]. Under the optimal condition of 20 nM GQDs-NPAb and a single pulse with 20 ms duration and 750 V/cm pulse intensity, the actual efficiency of labeling is ca. 34% and H1N1(GQDs) can retain 93% infectivity. Then, dual labeling of H1N1 was realized by labeling the envelope of H1N1(GQDs) with red QDs (RQDs) via a mild and efficient hydrazine-aldehyde-based strategy. At the optimal RQDs concentration of 5 nM, the actual efficiency of dual labeling can reach to 11% and the dual-labeled H1N1 can retain 93% infectivity. Because of the similar components and structure of different IAV subtypes, this dual-labeling strategy is applicable to other subtypes of IAV, e.g., H9N2.

Profiling the heterogeneous phenotypes of individual circulating tumor cells (CTCs) from patients is a very challenging task, but it paves new ways for cancer management, especially personalized anticancer therapy. Herein, we propose a chip-assisted multifunctional-nanosphere system for efficient and reliable biomarker phenotype analysis of individual heterogeneous CTCs. Red fluorescent magnetic biotargeting multifunctional nanospheres and green fluorescent biotargeting nanospheres targeting to two kinds of CTC biomarkers are used for convenient dual-fluorescence labeling of CTCs along with magnetic tags. By integrating magnetic enrichment with a size-selective single-cell-trapping microfluidic chip (SCT-chip), over 90% of CTCs, even when the concentrations is as low as 10 CTCs per milliliter of blood, can be individually trapped at highly ordered micropillars, spatially separated from the minimal residual blood cells. Such single CTCs offer easy-readout fluorescence signals, facilitating efficient identification and reliable phenotype analysis in accordance with their biomarker expressions. Therefore, the phenotypes of breast tumor cells in terms of the expression level of human epidermal-growth-factor receptor 2, an important target of clinical anticancer drugs, are accurately assessed, and over 82% of them can be classified into corresponding cell subpopulations. Furthermore, this system demonstrates successful detection and subpopulation analysis of heterogeneous CTCs from seven breast cancer patients, which provides a promising new means for single-cell profiling of CTC-biomarker phenotypes and guiding of personalized anticancer therapy.

Ebola virus (EBOV) disease is a complex zoonosis that is highly virulent in humans and has caused many deaths. Highly sensitive detection of EBOV is of great importance for early-stage diagnosis for increasing the probability of survival. Herein, we established a cellular-beacon-mediated counting strategy for an ultrasensitive EBOV assay on a micromagnetic platform. The detection platform, which was assisted by on-demand magnetic-field manipulation, showed high integration and enhanced complex-sample pretreatment by magnetophoretic separation and continuous-flow washing. Cellular beacons (i.e., fluorescent cells) with superior optical properties were used as reporters, and each cellular beacon was used as a fluorescent tracking unit to quantify EBOV by counting the numbers of individual fluorescent signals on the micromagnetic platform. This method achieves high sensitivity with a detection limit as low as 2.6 pg/mL, and the detection limit shows little difference in a complex matrix. In addition, it has excellent specificity and good reproducibility. These results indicate that this method proposes an ultrasensitive detection strategy for early diagnosis of the disease.

As a wise and profound teacher, nature provides numerous creatures with rich colors to us. To biomimic structural colors in nature as well as color changes responsive to environmental stimuli, there is a long way to go for the development of free-standing photonic films from natural polymers. Herein, a highly flexible, controllably iridescent, and multistimuli-responsive cellulose nanocrystal (CNC) film is prepared by simply introducing a small molecule as both plasticizer and hygroscopic agent. The presence of the additive does not block the self-assembly of CNC in aqueous solution but results in the enhancement of its mechanical toughness, making it possible to obtain free-standing iridescent CNC films with tunable structural colors. In response to environmental humidity and mechanical compression, such films can change structural colors smoothly by modulating their chiral nematic structures. Notably, the chromism is reversible by alternately changing relative humidity between 16 and 98%, mimicking the longhorn beetle Tmesisternus isabellae. This chromic effect enables various applications of the biofilms in colorimetric sensors, anticounterfeiting technology, and decorative coatings.

Electrochemistry has been widely used to explore fundamental properties of single molecules due to its fast response and high specificity. However, the lack of efficient signal amplification strategies and quantitative method limit its clinical application. Here, we proposed a digital single virus electrochemical enzyme-linked immunoassay (digital ELISA) for H7N9 avian influenza virus (H7N9 AIV) counting by integration of digital analysis, bifunctional fluorescence magnetic nanospheres (bi-FMNs) with monolayer gold nanoparticles (Au NPs) modified microelectrode array (MA). Bi-FMNs are fabricated by coimmobilizing polyclonal antibody (pAb) and alkaline phosphatase (ALP). At most, one target will be captured per bi-FMNs by controlling the proportion of bi-FMNs to target concentrations (≥5:1). The introduction of digital analysis can solve signal fluctuation and the reliability of single virus detection, enabling the digital ELISA to be sensitively and accurately applied for H7N9 AIV detection with a low detection limit of 7.8 fg/mL, which is greatly promising in single biomolecular detection, early diagnosis of disease, and practical application.

When infecting host cells, influenza virus must move on microfilaments (MFs) at the cell periphery and then move along microtubules (MTs) through the cytosol to reach the perinuclear region for genome release. But how viruses switch from the actin roadway to the microtubule highway remains obscure. To settle this issue, we systematically dissected the role of related motor proteins in the transport of influenza virus between cytoskeletal filaments in situ and in real-time using quantum dot (QD)-based single-virus tracking (SVT) and multicolor imaging. We found that the switch between MF- and MT-based retrograde motor proteins, myosin VI (myoVI) and dynein, was responsible for the seamless transport of viruses from MFs to MTs during their infection. After virus entry by endocytosis, both the two types of motor proteins are attached to virus-carrying vesicles. MyoVI drives the viruses on MFs with dynein on the virus-carrying vesicle hitchhiking. After role exchanges at actin-microtubule intersections, dynein drives the virus along MTs toward the perinuclear region with myoVI remaining on the vesicle moving together. Such a "driver switchover" mechanism has answered the long-pending question of how viruses switch from MFs to MTs for their infection. It will also facilitate in-depth understanding of endocytosis.

Rapid detection of highly contagious pathogens is the key to increasing the probability of survival and reducing infection rates. We developed a sensitive and quantitative lateral flow assay for detection of Ebola virus (EBOV) glycoprotein with a novel multifunctional nanosphere (RNs@Au) as a reporter. Each RNs@Au contains hundreds of quantum dots and dozens of Au nanoparticles and can achieve enhanced dual-signal readout (fluorescence signal for quantitative detection and colorimetric signal for visual detection). Antibody (Ab) and streptavidin (SA) were simultaneously modified onto the RNs@Au to label the target and act as signal enhancer. After the target was labeled by the Ab-RNs@Au-SA and captured on the test line, biotin-modified RNs@Au was used to amplify the dual signal by the reaction of SA with biotin. The assay enables naked-eye detection of 2 ng/mL glycoprotein within 20 min, and the quantitative detection limit is 0.18 ng/mL. Additionally, the assay has been successfully tested in field work for detecting EBOV in spiked urine, plasma, and tap water samples and is thus a promising candidate for early diagnosis of suspect infections in EBOV-stricken areas.

Monodisperse hydrophilic quantum dots (QDs) are promising labeling materials for biomedical applications. However, the controllable preparation of monodisperse hydrophilic QDs with amphiphilic polymers remains a challenge. Herein, the molecular structures of amphiphilic polymers assembled on different-sized QDs are investigated. Both the experimental results and the molecular dynamics (MD) calculation suggest that the grafting ratio of amphiphilic polymers assembled on QDs increases as the size of QDs increases. Thus, the controllable preparation of different-sized monodisperse hydrophilic QDs can be achieved by simply varying the grafting ratio of amphiphilic molecules and applied in the simultaneous labeling of three tumor biomarkers.

Aptamers have attracted much attention as the next generation of affinity reagents. Unfortunately, the selection efficiency remains a critical bottleneck for the widespread application of aptamers. Herein, to accelerate aptamers discovery, a multifunctional microfluidic selection platform was developed, on which the selection efficiency was greatly improved and high-affinity and -specificity aptamers were generated within two round selections. The multifunctional screening platform, precisely manipulating magnetic beads on the micrometer scale, improved selection performance based on microfluidic continuous flow and enhanced the selection process control via in situ monitoring and real-time evaluation. This method could suppress ∼50-fold nonspecific binding nucleic acids compared to the conventional methods, further eliminate weakly bound nucleic acids within 9 min, and simultaneously perform the negative selection and positive selection. And the selection effectiveness was in situ and real-time monitoring. Three aptamers showed high affinity and specificity toward mucin 1 (MUC1) with dissociation constants (K d ) in nanomolar range (from 22 to 65 nM). Furthermore, the selected aptamer was able to specially label cancer cells and efficiently capture exosomes with 64% capture efficiency. It demonstrated that the multifunctional screening platform was an efficient method to generate high-quality aptamers in a rapid and economic manner.

Entry is the first critical step for the infection of influenza A virus and of great significance for the research and development of antiflu drugs. Influenza A virus depends on exploitation of cellular endocytosis to enter its host cells, and its entry behaviors in distinct routes still need further investigation. With the aid of a single-virus tracking technique and quantum dots, we have realized real-time and multicolor visualization of the endocytic process of individual viruses and comprehensive dissection of two distinct dynamin-dependent endocytic pathways of influenza A virus, either dependent on clathrin or not. Based on the sequential progression of protein recruitment and viral motility, we have revealed the asynchronization in the recruitments of clathrin and dynamin during clathrin-dependent entry of the virus, with a large population of events for short-lived recruitments of these two proteins being abortive. In addition, the differentiated durations of dynamin recruitment and responses to inhibitors in these two routes have evidenced somewhat different roles of dynamin. Besides promoting membrane fission in both entry routes, dynamin also participates in the maturation of a clathrin-coated pit in the clathrin-dependent route. Collectively, the current study displays a dynamic and precise image of the entry process of influenza A virus and elucidates the mechanisms of distinct entry routes. This quantum dot-based single-virus tracking technique is proven to be well-suited for investigating the choreographed interactions between virus and cellular proteins.

As an ideal nanovector candidate, microvesicles (MVs) have been gradually utilized for packaging kinds of functional molecules for effective tumor diagnosis and therapy; however, the deficiency of their tumor targeting influenced their therapy efficacy. Through a facile phospholipid substitution strategy, MVs-based drug delivery system (DDS) was apparently endowed with high tumor targeting toward breast cancer thanks to the modified folate onto the membrane of MVs, simultaneously possessing a synergistic antitumor effect, and in vivo tumor imaging attributed to the SA-QDs labeling. Tumor killing effect could be improved up to 15 percentages with the help of the improved tumor targeting ability.

The 2014-16 Ebola virus (EBOV) outbreak in West Africa has attracted widespread concern. Rapid and sensitive detection methods are urgently needed for diagnosis and treatment of the disease. Here, we propose a novel method for EBOV detection based on efficient amplification of electroluminescent nanospheres (ENs) coupled with immunomagnetic separation. Uniform ENs are made by embedding abundant amounts of CdSe/ZnS quantum dots (QDs) into copolymer nanospheres through simple ultrasound. Compared to QDs, ENs can enhance electroluminescence (ECL) signals by approximately 85-fold, achieving a signal-to-background ratio high enough for EBOV detection. The introduction of magnetic nanobeads (MBs) can selectively separate targets from complex samples, simplifying the operation process and saving time. The presence of MBs can amplify ECL by approximately 3-fold, improving detection sensitivity. By integration of ENs with MBs, a sensitive electroluminescence biosensor is established for EBOV detection. The linear range is 0.02-30 ng/mL with a detection limit of 5.2 pg/mL. This method provides consistent reproducibility, specificity, and anti-interference ability and is highly promising in clinical diagnosis applications.

With unique and tunable photoluminescence (PL) properties, carbon nanodots (CNDs) as a new class of optical tags have been extensively studied. Because of their merits of controllability and sensitivity to the surface of nanomaterials, electrochemical methods have already been adopted to study the intrinsic electronic structures of CNDs. In this review, we mainly deal with the electrochemical researches of CNDs, including preparation, PL mechanism, and biosensing.