Single Effective Complex Loading into Zero-Mode Waveguides Optimized with Fluorescence Evaluation at Quenching and Accumulation Checkpoints.

Single-molecule detection with high accuracy and specialty plays an important role in biomedical diagnosis and screening. Zero-mode waveguides (ZMWs) enable the possibility of single biological molecule detection in real time. Nevertheless, the absence of a reliable assessment for single effective complex loading has constrained further applications of ZMWs in complex interaction. Both the quantity and activity of the complex loaded into ZMWs have a critical effect on the efficiency of detection. Herein, a fluorescence evaluation at quenching and accumulation checkpoints was established to assess and optimize single effective complex loading into ZMWs. A primer-template-enzyme ternary complex was designed, and then an evaluation for quantity statistics at the quenching checkpoint and functional activity at the accumulation checkpoint was used to validate the effectiveness of complexes loaded into ZMWs. By optimizing the parameters such as loading time, procedures, and enzyme amount, the single-molecule effective occupancy was increased to 25.48%, achieving 68.86% of the theoretical maximum value (37%) according to Poisson statistics. It is of great significance to provide effective complex-loading validation for improving the sample-loading efficiency of single-molecule assays or sequencing in the future.

Self-correction of cycle threshold values by a normal distribution-based process to improve accuracy of quantification in real-time digital PCR.

The digital polymerase chain reaction (dPCR) is a new and developing nucleic acid detection technology with high sensitivity that can realize the absolute quantitative analysis of samples. In order to improve the accuracy of quantitative results, real-time digital PCR emphasizes the kinetic information during amplification to identify prominent abnormal data. However, it is challenging to use a unified standard to accurately classify the amplification curve of each well as negative and positive, due to the interference caused by various factors in the experiment. In this work, a normal distribution-based cycle threshold value self-correcting model (NCSM) was established, which focused on the feature of the cycle threshold values in amplification curves and conducted continuous detection and correction on the whole. The cycle threshold value distribution was closer to the ideal normal distribution to avoid the influence of interference. Thus, the model achieves a more accurate classification between positive and negative results. The corrective process was applied to plasmid samples and resulted in an accuracy improvement from 92 to 99%. The coefficient of variation was below 5% when considering the quantitation of a range between 100 and 10,000 copies. At the same time, by utilizing this model, the distribution of cycle threshold values at the endpoint can be predicted with fewer thermal cycles, which can reduce the cycling time by around 25% while maintaining a consistency of more than 98%. Therefore, using the NCSM can effectively enhance the quantitative accuracy and increase the detection efficiency based on the real-time dPCR platform.

Efficient Simultaneous Detection of Metabolites Based on Electroenzymatic Assembly Strategy.

Objective and Impact Statement: We describe an electroenzymatic mediator (EM) sensor based on an electroenzymatic assembly peak separation strategy, which can efficiently realize the simultaneous detection of 3 typical cardiovascular disease (CVD) metabolites in 5 µl of plasma under one test. This work has substantial implications toward improving the efficiency of chronic CVD assessment. Introduction: Monitoring CVD of metabolites is strongly associated with disease risk. Independent and time-consuming detection in hospitals is unfavorable for chronic CVD management. Methods: The EM was flexibly designed by the cross-linking of electron mediators and enzymes, and 3 EM layers with different characteristics were assembled on one electrode. Electrons were transferred under tunable potential; 3 metabolites were quantitatively detected by 3 peak currents that correlated with metabolite concentrations. Results: In this study, the EM sensor showed high sensitivity for the simultaneous detection of 3 metabolites with a lower limit of 0.01 mM. The linear correlation between the sensor and clinical was greater than 0.980 for 242 patients, and the consistency of risk assessment was 94.6%. Conclusion: Metabolites could be expanded by the EM, and the sensor could be a promising candidate as a home healthcare tool for CVD risk assessment.

Model-Based Feedback Control for an Automated Micro Liquid Dispensing System Based on Contacting Droplet Generation through Image Sensing.

Over the past few decades, micro liquid dispensing technology has been widely used in biology, chemistry, material and environmental sciences due to its efficacy in processing multiple samples. For practical applications, precise and effective droplet generation is very important. Despite numerous droplet generation methods, the implementation of droplet-on-demand still faces challenges concerning system complexity, precision, cost, and robustness. In this work, a novel on-demand contacting droplet generation method incorporated with model-based feedback control with an image processing unit as a sensor was proposed. By studying droplet identification using image processing techniques, the model of droplet formation was simplified. Then model-based feedback control was implemented using volumes of dispensed samples as sensing signals by tuning related parameters adaptively to resist disturbances. The proposed method was integrated and applied to a homebuilt automated micro liquid dispensing system with droplets ranging from 20 nanoliter to 200 nanoliter. The experimental results demonstrated a high degree of accuracy and precision. Additionally, the proposed system's practical utility was evaluated by analyzing mutations in genes associated with sensorineural hearing loss, verifying its effectiveness.

Revealing the Binding Events of Single Proteins on Exosomes Using Nanocavity Antennas beyond Zero-Mode Waveguides.

Exosomes (EXOs) play a crucial role in biological action mechanisms. Understanding the biological process of single-molecule interactions on the surface of the EXO membrane is essential for elucidating the precise function of the EXO receptor. However, due to dimensional incompatibility, monitoring the binding events between EXOs of tens to hundreds of nanometers and biomolecules of nanometers using existing nanostructure antennas is difficult. Unlike the typical zero-mode waveguides (ZMWs), this work presents a nanocavity antenna (λvNAs) formed by nanocavities with diameters close to the visible light wavelength dimensions. Effective excitation volumes suitable for observing single-molecule fluorescence were generated in nanocavities of larger diameters than typical ZMWs; the optimal signal-to-noise ratio obtained was 19.5 when the diameter was 300 nm and the incident angle was ∼50°. EXOs with a size of 50-150 nm were loaded into λvNAs with an optimized diameter of 300-500 nm, resulting in appreciable occupancy rates that overcame the nanocavity size limitation for large-volume biomaterial loading. Additionally, this method identified the binding events between the single transmembrane CD9 proteins on the EXO surface and their monoclonal antibody anti-CD9, demonstrating that λvNAs expanded the application range beyond subwavelength ZMWs. Furthermore, the λvNAs provide a platform for obtaining in-depth knowledge of the interactions of single molecules with biomaterials ranging in size from tens to hundreds of nanometers.

Distinct ferrovalley characteristics of the Janus RuClX (X = F, Br) monolayer.

Two-dimensional ferrovalley materials should simultaneously possess three characteristics, that is, a Curie temperature beyond atmospheric temperature, perpendicular magnetic anisotropy, and large valley polarization for potential commercial applications. In this report, we predict two ferrovalley Janus RuClX (X = F, Br) monolayers by first-principles calculations and Monte Carlo simulations. The RuClF monolayer exhibited a valley-splitting energy as large as 194 meV, perpendicular magnetic anisotropy energy of 187 µeV per f.u., and Curie temperature of 320 K. Thus, spontaneous valley polarization at room temperature will be present in the RuClF monolayer, which is nonvolatile for spintronic and valleytronic devices. Although the valley-splitting energy of the RuClBr monolayer was as high as 226 meV with magnetic anisotropy energy of 1.852 meV per f.u., the magnetic anisotropy of the RuClBr monolayer was in-plane, and its Curie temperature was only 179 K. The orbital-resolved magnetic anisotropy energy revealed that the interaction between the occupied spin-up states of dyz and the unoccupied spin-down states of dz2 dominated the out-of-plane magnetic anisotropy in the RuClF monolayer, but the in-plane magnetic anisotropy of the RuClBr monolayer was mostly contributed by the coupling of the dxy and dx2-y2 orbitals. Interestingly, the valley polarizations in the Janus RuClF and RuClBr monolayers appeared in their valence band and conduction band, respectively. Thus, two anomalous valley Hall devices are proposed using the present Janus RuClF and RuClBr monolayers with hole and electron doping, respectively. This study provides interesting and alternative candidate materials for the development of valleytronic devices.

A duplex-specific nuclease assisted photoelectrochemical biosensor based on MoS2@ReS2/Ti3C2 hybrid for ultrasensitive detection of colorectal cancer-related piRNA-31,143.

piR-31,143 has been identified as a potential biomarker for the diagnosis of colorectal cancer (CRC). However, the current detection methods have complicated operations and high cost, which restrict its clinical application. In the present work, we reported a new photoelectrochemical (PEC) biosensor based on MoS2@ReS2/Ti3C2 hybrid and duplex-specific nuclease (DSN) assisted signal amplification mechanism for ultrasensitive detection of piRNA-31,143 from human serum. The formation of the type I heterostructure between MoS2 and ReS2 and the doping of Ti3C2 contributed to high photocurrent response. The presence of piR-31,143 triggered the chain displacement reaction and enzymatic cyclic amplification reaction on the electrode surface with the assistance of DSN, leading to the collapse of the composite probe system. Consequently, the photocurrent of the PEC biosensor was proportional to the concentration of piR-31,143. The linear detection range and calculated detection limit of the PEC biosensor were 10-1-106 fM and 23 aM, respectively. The stability of the photocurrent under 15 consecutive on-off irradiations (with a relative standard deviation of 1.17%) and the specific response to piR-31,143 demonstrated the reliability of the PEC biosensor. In addition, the practicability of the PEC biosensor was verified by batch detection of human serum. The area under the receiver operating characteristic curve used to distinguish CRC patients from healthy controls was 0.942 with 100% specificity, demonstrating the developed method is a promising approach for the diagnosis of CRC. STATEMENT OF SIGNIFICANCE: The clinical translation of piRNAs for cancer diagnosis is hindered by efficacy of detection techniques due to tedious sample processing and costly instrumentation. Herein, we fabricated a photoelectrochemical biosensor for the ultrasensitive detection of piR-31,143 with 10 µL serum in vitro. MoS2@ReS2/Ti3C2 greatly enhances the photocurrent response while duplex-specific nuclease improves the detection sensitivity and avoids false positives. By transforming the recognition sequence of the probe, the sensor can be applied to a variety of piRNAs detection for different diseases. In addition, the electrode can be recycled which is beneficial to reduce the cost of detection. With suitable automation and further optimization, our work may serve as core component in the development of an accurate and efficient diagnosis method.

Highly Sensitive Exosome Detection for Early Diagnosis of Pancreatic Cancer Using Immunoassay Based on Hierarchical Surface-Enhanced Raman Scattering Substrate.

Exosomes have emerged as potential biomarkers for pancreatic cancer (PaC). However, it is still challenging to get quantitative detection of exosomes with the specific surface receptors. In this study, a highly sensitive detection system is first constructed for the direct quantitation of specific exosomes in real samples using hierarchical surface-enhanced Raman scattering substrate (H-SERS substrate) and rapid enrichment strategy magnetic beads @ exosomes @ SERS detection probes (MEDP). It is found that the detection system (MEDP @ H-SERS substrate) could provide a 3.5 times higher SERS intensity compared with MEDP sandwich immunocomplex only. Moreover, LRG1-positive exosomes (LRG1-Exos) and GPC1-positive exosomes (GPC1-Exos) are chosen to distinguish PaC through exosome proteomics and database screening. The lower limit of detection (LOD) is 15 particles µL-1 using the MEDP @ H-SERS substrate. Significantly, the detection in clinical samples shows that the innovative combination of LRG1-Exos and GPC1-Exos could improve the diagnostic efficiency of PaC, with an area under the operating characteristic curve (AUC) of 0.95. Even for the early-stage PaC, the diagnostic accuracy is still high (AUC = 0.95). Collectively, the findings indicate that the MEDP @ H-SERS substrate has great potential for the early diagnosis of PaC.

Integrated microdevice with a windmill-like hole array for the clog-free, efficient, and self-mixing enrichment of circulating tumor cells.

Circulating tumor cells (CTCs) have tremendous potential to indicate disease progression and monitor therapeutic response using minimally invasive approaches. Considering the limitations of affinity strategies based on their cost, effectiveness, and simplicity, size-based enrichment methods that involve low-cost, label-free, and relatively simple protocols have been further promoted. Nevertheless, the key challenges of these methods are clogging issues and cell aggregation, which reduce the recovery rates and purity. Inspired by the natural phenomenon that the airflow around a windmill is disturbed, in this study, a windmill-like hole array on the SU-8 membrane was designed to perturb the fluid such that cells in a fluid would be able to self-mix and that the pressure acting on cells or the membrane would be dispersed to allow a greater velocity. In addition, based on the advantages of fluid coatings, a lipid coating was used to modify the membrane surface to prevent cell aggregation and clogging of the holes. Under the optimal conditions, recovery rates of 93% and 90% were found for A549 and HeLa cells in a clinical simulation test of our platform with a CTC concentration of 20-100 cells per milliliter of blood. The white blood cell (WBC) depletion rate was 98.7% (n = 15), and the CTC detection limit was less than 10 cells per milliliter of blood (n = 6). Moreover, compared with conventional membrane filtration, the advantages of the proposed device for the rapid (2 mL/min) and efficient enrichment of CTCs without clogging were shown both experimentally and theoretically. Due to its advantages in the efficient, rapid, uniform, and clog-free enrichment of CTCs, our platform offers great potential for metastatic detection and therapy analyses.

The heparinase-linked differential time method allows detection of heparin potency in whole blood with high sensitivity and dynamic range.

Anticoagulation therapy with heparin is an effective treatment against thrombosis. Heparin tends to cause spontaneous bleeding and requires regular monitoring during therapy. Most high-sensitivity heparin sensors have focused on the concentration detection in clarified buffer solution. However, the pharmacodynamics of heparin vary depending on individual patient or disease, while potency detection with high sensitivity and dynamic range outperforms concentration detection in clinical diagnosis. In this study, a novel heparinase-linked differential time (HLDT) method was established with a two-zone of Graphene modified Carbon (GR-C) sensor, which was utilized to evaluate heparin potency in whole blood. It was based on electrochemical measurement of clotting time shifting associated with presence or absence of heparinase. Heparinase inhibits the anticoagulant ability of heparin by forming a heparin-antithrombin-thrombin complex during coagulation. And the intensity and peak time of electrochemical current were associated with thrombin activity and clotting on the electrode. The results demonstrated that the sensor had high selectivity for heparin potency in 10 µL of whole blood with a detection limit of 0.1 U/mL, and the linear detection range was 0.1-5 U/mL. The coefficient of variation (CV) of the peak time was less than 5%, and linear correlation between the GR-C sensor and the TEG-5000 instrument was 0.987. Thus, the HLDT method has better clinical application due to its good repeatability, high sensitivity and wide range in heparin potency evaluation.

The development of real-time digital PCR technology using an improved data classification method.

For digital polymerase chain reaction (PCR), data classification is always a crucial task. The dynamic real-time amplification process information of each partition is always ignored in typical digital PCR analysis, which can easily lead to inaccurate outcomes. In this work, an integrated device that offers real-time chip-based digital PCR analysis was established. In addition, an enhanced process-based classification model (PAM) was built and trained. And then the device and the analytical model were employed in classification tasks for different concentrations of Epstein-Barr Virus (EBV) plasmid quantification assays. The results indicated that the real-time analysis device achieved a linearity of 0.97, the classification method was able to distinguish the false-positive curves, and the recognition error of positive wells was decreased by 64.4% compared with typical static analysis techniques when low concentrations of samples were tested. With these advantages, it is supposed that the real-time digital PCR analysis apparatus and the improved classification method can be employed to enhance the performance of digital PCR technology.

Full-Electrical Writing and Reading of Magnetization States in a Magnetic Junction with Symmetrical Structure and Antiparallel Magnetic Configuration.

Full-electrical writing and reading of magnetization states are vital for the development of next-generation spintronic devices with high density and ultralow-power consumption. Here, we proposed a method to realize the full-electrical writing and reading of magnetization states via a structural design, which only requires a symmetrical device structure and an antiparallel magnetic configuration. CrBr3, h-BN, and 1T-MnSe2 were selected to construct the device of CrBr3/h-BN/1T-MnSe2/h-BN/CrBr3, where the magnetization of two CrBr3 layers was fixed to the antiparallel state. By changing the direction and magnitude of the applied electric field, it is proved that the magnetization of 1T-MnSe2 could be reversed. Moreover, the device energies before and after the magnetization reversal are the same when the applied electric field is removed due to the structural symmetry. Meanwhile, the magnetic anisotropy energy of 1T-MnSe2 could induce an energy barrier, to guarantee the nonvolatile magnetization reversal in the present device. In addition, the tunnel magnetoresistance ratio was found up to 421%, showing a promising application to full-electrically write and read magnetization in spintronics. The present study likely promotes the development of full-electrical and ultralow-power spintronics devices.

A rapid variant-tolerant reverse transcription loop-mediated isothermal amplification assay for the point of care detection of HIV-1.

Human immunodeficiency virus (HIV) continues to be a major burden on public health globally with on-going increases in the number of new infections each year. Rapid and sensitive point-of-care tests allow timely interventions and are essential to control the spread of the disease. However the highly variable nature of the virus, resulting in the evolution of many subtypes and inter-subtype recombinants, poses important challenges for its diagnosis. Here we describe a variant-tolerant reverse-transcription RT-LAMP amplification of the virus's INT gene, providing a simple to use, rapid (<30 min) in vitro point-of-care diagnostic test with a limit of detection <18 copies/reaction. The assay was first validated in clinical studies of patient samples, using both established RT-LAMP and RT-qPCR assays for reference, with results showing that this new variant-tolerant HIV-1 RT-LAMP diagnostic test is highly sensitive without compromising its high specificity for HIV-1 subtypes. The diagnostic test was subsequently configured within an easy-to-read paper microfluidic lateral flow test and was validated clinically using patient samples, demonstrating its future potential for use in timely, effective, low cost HIV diagnostics in global regions where healthcare resources may be limited.

A Novel 2-dimensional Multiplex qPCR Assay for Single-Tube Detection of Nine Human Herpesviruses.

Human herpesviruses are double-stranded DNA viruses that are classified into nine species. More than 90% of adults are ever infected with one or more herpesviruses. The symptoms of infection with different herpesviruses are diverse ranging from mild or asymptomatic infections to deadly diseases such as aggressive lymphomas and sarcomas. Timely and accurate detection of herpesvirus infection is critical for clinical management and treatment. In this study, we established a single-tube nonuple qPCR assay for detection of all nine herpesviruses using a 2-D multiplex qPCR method with a house-keeping gene as the internal control. The novel assay can detect and distinguish different herpesviruses with 30 to 300 copies per 25 µL single-tube reaction, and does not cross-react with 20 other human viruses, including DNA and RNA viruses. The robustness of the novel assay was evaluated using 170 clinical samples. The novel assay showed a high consistency (100%) with the single qPCR assay for HHVs detection. The features of simple, rapid, high sensitivity, specificity, and low cost make this assay a high potential to be widely used in clinical diagnosis and patient treatment.

Cadmium chloride-induced transgenerational neurotoxicity in zebrafish development.

As an important environmental pollutant, the heavy metal cadmium has a significant negative impact on the stability of the ecological environment and on organismal health. Previous studies have shown that cadmium chloride can damage the nervous, skeletal, endocrine, and reproductive systems, but to our knowledge, the effects of cadmium on the behavior, neurotransmitter levels, and neuronal development in the offspring of exposed animals have not been reported. In the present study, sexually-mature zebrafish were exposed to cadmium chloride at different concentrations for 60 days, and in this background, behavior, neurotransmitters level, neuro-development and neurotransmitter metabolism was investigated in the F1 offspring. The results showed that exposure of the parental zebrafish to cadmium chloride resulted swimming speed and distance of F1 offspring significantly reduced; the levels of neurotransmitters, such as dopamine, serotonin, and acetylcholine is disrupted. neuro-development and neurotransmitter metabolism related genes expression pattern was altered, which cause zebrafish F1 offspring developmental neurotoxicity. These findings provide further insights into the harm posed by cadmium chloride to the aquatic ecosystems.

High filling rate digital PCR through-hole array chip with double independent S-shaped flow channels.

Sample digital technology is a powerful method for absolute quantification of target molecules such as nucleic acids and proteins. The excellent sample stability and mass production capability has enabled the development of microwell array-based sample digitizing methods. However, in current microwell array chips, samples are loaded by the liquid scraping method, which requires complex manual operation and results in a low filling rate and limited hole filling uniformity. Here, we perform sample loading of a through-hole array chip by a microfluidics-driven method and design a double independent S-shaped flow channels sandwiched through-hole array chip. Because of the capillary force and capillary burst pressure, the sample flowing in the channel can be trapped into through-holes, but cannot flow through the other side. Via air flow and displacement of the remaining sample in the channel, the sample can be partitioned consistently, with zero surplus sample residue in the channel. We evaluated the actual performance of the sample-loading process: the chip enables 99.10% filling rate of 18 500 through-holes, with a grayscale coefficient of variation value of 6.03% determined from fluorescence images. In performing digital polymerase chain reaction on chip, the chip demonstrates good performance for the absolute quantification of target DNA. The simple and robust design of our chip, with excellent filling rate and microsample uniformity, indicates potential for use in a variety of sample digitization applications.

Interface hybridization and spin filter effect in metal-free phthalocyanine spin valves.

Spin-orbit coupling (SOC) has long been regarded as the core interaction to determine the efficiency of spin conserved transport in semiconductor spintronics. In this report, a spin-valve device with a Co/metal-free phthalocyanine (H2Pc)/Co stacking structure is fabricated. The magnetoresistance effect was successfully obtained in the device. It is also found that the magnetoresistance response is relatively smaller than that of metallic phthalocyanines, clearly implying that SOC is not the key factor to affect the magnetoresistance in phthalocyanine spin-valves. The dominant mechanism that determines the spin transport efficiency in the present H2Pc devices was systemically explored by combining both experimental measurements and first-principles calculation analysis. It was noticed that both the crystalline structure and molecular orientation of the H2Pc layer could be modified by the contact under-layer materials, which changes the magnetization intensity of the ferromagnetic metallic electrode due to the strong interface hybridization of Co/H2Pc. Meanwhile, the theoretical calculations clearly demonstrated that the spin filter effect from the second H2Pc layer should be responsible for the decrease of the magnetoresistance response in the present spin-valves compared to those using metallic phthalocyanine layers. This investigation may trigger new insights into the role of SOC strength and interface hybridization in organic spintronics.

Parental exposure to cadmium chloride causes developmental toxicity and thyroid endocrine disruption in zebrafish offspring.

Cadmium is a common heavy metal pollutant. Previous studies have found that long-term cadmium exposure can cause damage to multiple organs/systems in humans and experimental animals; however, there are few studies that elucidate its effects on offspring development, discuss whether it can be transmitted to offspring from the parent, and debate whether it affects the functional development of the thyroid hormone system in offsprings. In this study, sexually mature zebrafish were exposed to different concentrations of cadmium chloride (0.01 µmol/L, 0.1 µmol/L, and 1 µmol/L) to study reproductive toxicity. It was found that parental zebrafish exposed to 1 µmol/L of cadmium chloride produced offsprings with different degrees of malformation. At 5 days post-fertilization (dpf), the levels of 3,5,3'-triiododenosine (T3) and thyroxine (T4) in the zebrafish were decreased. At 10 dpf, the T4 and T3 levels in the zebrafish of the offspring were significantly reduced. At the same time, the expression of thyroid receptor (trα and trß) genes in five dpf larvae was significantly up-regulated in the 1 µmol/L treatment group relative to the control group. The mRNAs of thyroid hormone synthesis and metabolism-related genes (tshß, dio1, dio2, ugt1ab, and ttr) were significantly up-regulated in the 0.1 µmol/L and 1 µmol/L treatment groups. This study demonstrates that parental cadmium chloride exposure produces reproductive toxicity in zebrafish and that the effects can be transferred from the parent to the offspring, resulting in developmental toxicity in the thyroid endocrine system.

Heterogeneous modification of through-hole microwell chips for ultralow cross-contamination digital polymerase chain reaction.

Chip-based dPCR (cdPCR) with a physical boundary between micro-units allows for high parallelism, robustness and sensitivity. However, cross-contamination between micro-units is still a problem that affects the accuracy of results. To overcome this problem, we introduced a heterogeneous modification strategy by microcontact printing to prepare a through-hole microwell chip (TMC) with a hydrophobic exterior surface and hydrophilic interior surface. The modified TMC can reduce cross-contamination (sample residual rate (SRR) of (4.9 ± 1.5)%) by an efficient partitioning yield (unit filling rate (UFR) of (91.1 ± 2.2)%). The sample-residual properties of modified TMCs could be tuned by the reaction conditions. As the contact time increased, the surface CA of the TMC increased, which caused decreases of the SRR and UFR. However, prolonging the contact time to 25 s would cause a sharp reduction of the UFR. The modified TMCs with high UFRs were used for further dPCR studies. The fluorescence images of dPCR chips were collected by fluorescence microscopy and a self-developed optical system, followed by image processing and data statistics to obtain quantitative results. The copy number variation results of the surface hydrophobic TMC was closer to the true value compared to that of the hydrophilic TMC. The results indicated that the sample residue on the hydrophilic TMC would increase the number of positive points, which would cause false positives and clustering error. The absolute quantitative results of gradient dilution plasmid DNA of JAK2 gene using modified TMC also proved that heterogeneous modification made the quantitative results more accurate. The heterogeneous modified TMC is expected to be used for high-throughput, high-sensitivity and high-specificity biological analyses, such as circulating tumor DNA and cell analysis.

Surface/Interface Engineering for Constructing Advanced Nanostructured Photodetectors with Improved Performance: A Brief Review.

Semiconductor-based photodetectors (PDs) convert light signals into electrical signals via a photon-matter interaction process, which involves surface/interface carrier generation, separation, and transportation of the photo-induced charge media in the active media, as well as the extraction of these charge carriers to external circuits of the constructed nanostructured photodetector devices. Because of the specific electronic and optoelectronic properties in the low-dimensional devices built with nanomaterial, surface/interface engineering is broadly studied with widespread research on constructing advanced devices with excellent performance. However, there still exist some challenges for the researchers to explore corresponding mechanisms in depth, and the detection sensitivity, response speed, spectral selectivity, signal-to-noise ratio, and stability are much more important factors to judge the performance of PDs. Hence, researchers have proposed several strategies, including modification of light absorption, design of novel PD heterostructures, construction of specific geometries, and adoption of specific electrode configurations to modulate the charge-carrier behaviors and improve the photoelectric performance of related PDs. Here, in this brief review, we would like to introduce and summarize the latest research on enhancing the photoelectric performance of PDs based on the designed structures by considering their surface/interface engineering and how to obtain advanced nanostructured photo-detectors with improved performance, which could be applied to design and fabricate novel low-dimensional PDs with ideal properties in the near future.