Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Humidity Sensing of Stretchable and Transparent Hydrogel Films for Wireless Respiration Monitoring

Respiratory monitoring plays a pivotal role in health assessment and provides an important application prospect for flexible humidity sensors.However,traditional humidity sensors suffer from a trade-off between deformability,sensitivity,and transparency,and thus the development of high-performance,stretchable,and low-cost humidity sensors is urgently needed as wearable electronics.Here,ultrasensitive,highly deformable,and transparent humidity sensors are fabricated based on cost-effective polyacrylamide-based double network hydrogels.Concomitantly,a general method for preparing hydrogel films with controllable thickness is proposed to boost the sensitivity of hydrogel-based sensors due to the extensively increased specific surface area,which can be applied to different polymer networks and facilitate the development of flexible integrated electronics.In addition,sustainable tapioca rich in hydrophilic polar groups is introduced for the first time as a second cross-linked network,exhibiting excellent water adsorption capacity.Through the synergistic optimization of structure and composition,the obtained hydrogel film exhibits an ultrahigh sensitivity of 13,462.1%/%RH,which is unprecedented.Moreover,the hydrogel film-based sensor exhibits excellent repeatability and the ability to work normally under stretching with even enhanced sensitivity.As a proof of concept,we integrate the stretchable sensor with a specially designed wireless circuit and mask to fabricate a wireless respiratory interruption detection system with Bluetooth transmission,enabling real-time monitoring of human health status.This work provides a general strategy to construct high-performance,stretchable,and miniaturized hydrogel-based sensors as next-generation wearable devices for real-time monitoring of various physiological signals.

Effects of Estrogen on ER, NGF, and ChAT Expression in Cerebellum of Aging Female Sprague-Dawley Rat

This article discusses the effects of estrogen on the expression of estrogen receptor （ER）, nerve growth factor （NGF）, and choline acetyltransferase （CHAT） in the cerebellum of rats. The model of aging female rat was established to study the expression and distribution of ER, NGF, and ChAT in the cerebellum following 17β-estradiol treatment using the technique of immunohistochemical ultrasensitive SP in sprague-dawley rat. The immunoreactive productions were distributed in stratum Purkinje cell, nucleus dentatus, nucleus interpositus, and nucleus fastigii of cerebellum, and the ER positive production was mainly located in the plasma, cytoplasmic membrane, and neurite, and also existed in nucleus. The general tendency of the expression of ER, NGF, and ChAT positive production in the cerebellum cortex and nuclei of aging rat significantly decreases, while the intensity and quantity of the immunoreactive production ascends predominantly after 17β-estradiol treatment. Simultaneously, the positive neurite of Purkinje cell shows a similar tendency. The above- mentioned results suggest that the estrogen upregulates the expression of NGF and CHAT, and plays a vital role in sustaining and protecting the structure and function of cerebellum neurons. Furthermore, the similarity of their changing tendency implies that they were correlated and cooperated during the course in effect of estrogen on cerebellum. It also showed that the action of estrogen in cerebellum could be via genomic and nongenomic mechanism.

Relay-type sensing mode:A strategy to push the limit on nanomechanical sensor sensitivity based on the magneto lever

Ultrasensitive molecular detection and quantization are crucial for many applications including clinical diagnostics,functional proteomics,and drug discovery;however,conventional biochemical sensors cannot satisfy the stringent requirements,and this has resulted in a long-standing dilemma regarding sensitivity improvement.To this end,we have developed an ultrasensitive relay-type nanomechanical sensor based on a magneto lever.By establishing the link between very weak molecular interaction and five orders of magnitude larger magnetic force,analytes at ultratrace level can produce a clearly observable mechanical response.Initially,proof-of-concept studies showed an improved detection limit up to five orders of magnitude when employing the magneto lever,as compared with direct detection using probe alone.In this study,we subsequently demonstrated that the relay-type sensing mode was universal in application ranging from micromolecule to macromolecule detection,which can be easily extended to detect enzymes,DNA,proteins,cells,viruses,bacteria,chemicals,etc.Importantly,we found that,sensitivity was no longer subject to probe affinity when the magneto lever was sufficiently high,theoretically,even reaching single-molecule resolution.

Detecting nanoparticles by“listening”

In the macroscopic world,we can obtain some important information through the vibration of objects,that is,listening to the sound.Likewise,we can also get some information of the nanoparticles that we want to know by the means of“listening”in the microscopic world.In this review,we will introduce two sensing methods(cavity optomechanical sensing and surface-enhanced Raman scattering sensing)which can be used to detect the nanoparticles.The cavity optomechanical systems are mainly used to detect sub-gigahertz nanoparticle or cavity vibrations,while surface-enhanced Raman scattering is a well-known technique to detect molecular vibrations whose frequency generally exceeds terahertz.Therefore,the vibrational information of nanoparticles from low-frequency to high-frequency could be obtained by these two methods.The size of the viruses is at the nanoscale and we can regard it as a kind of nanoparticles.Rapid and ultrasensitive detection of the viruses is the key strategies to break the spread of the viruses in the community.Cavity optomechanical sensing enables rapid,ultrasensitive detection of nanoparticles through the interaction of light and mechanical oscillators and surface-enhanced Raman scattering is an attractive qualitatively analytical technique for chemical sensing and biomedical applications,which has been used to detect the SARS-CoV-2 infected.Hence,investigation in these two fields is of vital importance in preventing the spread of the virus from affecting human’s life and health.

Ultrasensitive polarization-dependent terahertz modulation in hybrid perovskites plasmoninduced transparency devices

Active control of metamaterial properties with high tunability of both resonant intensity and frequency is essential for advanced terahertz(THz) applications, ranging from spectroscopy and sensing to communications.Among varied metamaterials, plasmon-induced transparency(PIT) has enabled active control with giant sensitivity by embedding semiconducting materials. However, there is still a stringent challenge to achieve dynamic responses in both intensity and frequency modulation. Here, an anisotropic THz active metamaterial device with an ultrasensitive modulation feature is proposed and experimentally studied. A radiative-radiative-coupled PIT system is established, with a frequency shift of 0.26 THz in its sharp transparent windows by polarization rotation. Enabled by high charge-carrier mobility and longer diffusion lengths, we utilize a straightforwardly spincoated MAPbI3 film acting as a photoactive medium to endow the device with high sensitivity and ultrafast speed.When the device is pumped by an ultralow laser fluence, the PIT transmission windows at 0.86 and 1.12 THz demonstrate a significant reduction for two polarizations, respectively, with a full recovery time of 561 ps. In addition, we numerically prove the validity that the investigated resonator structure is sensitive to the optically induced conductivity. The hybrid system not only achieves resonant intensity and frequency modulations simultaneously, but also preserves the all-optical-induced switching merits with high sensitivity and speed, which enriches multifunctional subwavelength metamaterial devices at THz frequencies.

Ultrasensitive Detection and Binding Mechanism of Cocaine in an Aptamer-based Single-molecule Device

Aptamer serves as a potential candidate for the micro-detection of cocaine due to its high specificity,high affinity and good stability.Although cocaine aptasensors have been extensively studied,the binding mechanism of cocaine-aptamer interactions is still unknown,which limits the structural refinement in the design of an aptamer to improve the performance of cocaine aptasensors.Herein,we report a label-free,ultrasensitive detection of single-molecule cocaine-aptamer interaction by using an electrical nanocircuit based on graphene-moleculegraphene single-molecule junctions (GMG-SMJs).Real-time recordings of cocaine-aptamer interactions have exhibited distinct current oscillations before and after cocaine treatment,revealing the dynamic mechanism of the conformational changes of aptamer upon binding with cocaine.Further concentration-dependent experiments have proved that these devices can act as a single-molecule biosensor with at least a limit of detection as low as 1 nmol·L^-1.The method demonstrated in this work provides a novel strategy for shedding light on the interaction mechanism of biomolecules as well as constructing new types of aptasensors toward practical applications.

DNA hybridization chain reaction and DNA supersandwich self-assembly for ultrasensitive detection

The fabrication of sensitive sensors with high selectivity is highly desirable for the detection of some important biomarkers,such as nucleic acids,proteins,small molecules and ions.DNA hybridization chain reaction(HCR) and DNA supersandwich self-assembly(SSA) are two prevalent enzyme-free signal amplification strategies to improve sensitivity of the sensors.In this review,we firstly describe the characteristics about DNA HCR and DNA SSA,and then summarize the advances in the one-dimensional DNA nanostructures assisted by HCR and SSA.This review has been divided into three parts according to the two signal amplification methods and highlights recent progress in these two strategies to improve the detection sensitivity of proteins,nucleic acids,small molecules and ions.

Ultrasensitive terahertz metamaterial sensor based on vertical split ring resonators

An ultrasensitive metamaterial sensor based on double-slot vertical split ring resonators(DVSRRs) is designed and numerically calculated in the terahertz frequency. This DVSRR design produces a fundament LC resonance with a quality factor of about 20 when the incidence magnetic field component normal to the DVSRR array. The resonant characteristics and sensing performance of the DVSRR array design are systematically analyzed employing a contrast method among three similar vertical split ring resonator(SRRs) structures. The research results show that the elimination of bianisotropy, induced by the structural symmetry of the DVSRR design, helps to achieve LC resonance of a high quality factor. Lifting the SRRs up from the substrate sharply reduces the dielectric loss introduced by the substrate. All these factors jointly result in superior sensitivity of the DVSRR to the attributes of analytes. The maximum refractive index sensitivity is 788 GHz/RIU or 1.04 × 10~5 nm∕RIU.Also, the DVSRR sensor maintains its superior sensing performance for fabrication tolerance ranging from -4% to 4% and wide range incidence angles up to 50° under both TE and TM illuminations.

Ultrasensitive magnetic field sensor based on an in-fiber Mach–Zehnder interferometer with a magnetic fluid component

An ultrasensitive magnetic field sensor based on a compact in-fiber Mach–Zehnder interferometer(MZI) created in twin-core fiber(TCF) is proposed, and its performance is experimentally demonstrated. A section of TCF was spliced between two sections of standard single-mode fibers, and then a microchannel was drilled through one core of the TCF by means of femtosecond laser micromachining. The TCF with one microchannel was then immersed in a water-based Fe_3O_4 magnetic fluid(MF), forming a direct component of the light propagation path,and then sealed in a capillary tube, achieving a magnetic sensing element, which merges the advantages of an MZI with an MF. Experiments were conducted to investigate the magnetic response of the proposed sensor. The developed magnetic field sensor exhibits a linear response within a measurement range from 5 to 9.5 m T and an ultrahigh sensitivity of 20.8 nm/m T, which, to our best knowledge, is 2 orders of magnitude greater than other previously reported magnetic sensors. The proposed sensor is expected to offer significant potential for detecting weak magnetic fields.

Ultrasensitive biosensors based on long-range surface plasmon polariton and dielectric waveguide modes

An ultrasensitive biosensor based on hybrid structure and composed of long-range surface plasmon polariton(LRSPP) and dielectric planar waveguide(PWG) modes is proposed. Both PWG and LRSPP modes have strong resonances to form strong coupling between the two modes, and the two modes can couple to enhance sensitivity of sensors. In the hybrid structure, PWG is composed of cytop–Si–cytop multilayers and the LRSPP configuration is composed of cytop–metal–sensing medium multilayer slabs. The highest imaging sensitivities of 2264 and3619 RIU-1were realized in the proposed sensors based on Au and Al-monolayer graphene, respectively, which are nearly 1.2 and 1.9 times larger than the 1910 RIU-1sensitivity of the conventional LRSPR sensor(LRSPP sensor). Moreover, it is demonstrated that the PWG-coupled LRSPP biosensor is applicable to the sensing medium,with refractive index in the vicinity of 1.34.

基于离子导电双网络水凝胶薄膜的超灵敏、可拉伸、透明湿度传感器

本工作中,我们在可拉伸的弹性基底上集成了厚度可控的可拉伸、透明的双网络导电水凝胶薄膜,它具有很好的环境稳定性以及对湿度极高的响应灵敏度(78,785.5%/%RH).与块体水凝胶相比,基于水凝胶薄膜的湿度传感器对98%RH的响应提高了2×10^(5)倍,另外,响应和恢复速度分别提高了5.9倍和7.6倍.这得益于水凝胶薄膜超高的比表面积,丰富的活性吸附位点以及短的扩散距离.研究发现水凝胶的湿度传感性能具有显著的厚度依赖性.系统的湿敏机理研究表明:水分子的吸附提高了水凝胶的离子迁移率和介电常数,并且形成了双电层,从而实现了对湿度的超高电学响应.此外,该传感器能够实现非接触式人机交互以及实时地检测人体呼吸.这项工作为实现器件性能的突破以及推动水凝胶基集成微电子技术的发展提供了新策略.

Ultrasensitive and accurate diagnosis of urothelial cancer by plasmonic AuNRs-enhanced fluorescence of near-infrared Ag_(2)S quantum dots

Urothelial carcinoma(UC)is a common malignant tumor in the urinary system with high recurrence rate and low survival rate 5 years after surgery.At present,imaging examination and other diagnostic methods have some shortcomings such as invasiveness and non-specificity.Therefore,it is urgent to develop a simple,rapid,noninvasive,highly sensitive and highly specific strategy to diagnose UC.Herein,a high-performance fluorescence sensor was constructed by the plasmonic gold nanorods(AuNRs)-enhanced near-infrared(NIR)fluorescence of silver sulfide quantum dots(Ag_(2)S QDs).The designed sensor can be used for the fast and accurate detection of small molecule single-transmembrane protein(FXYD3),which is overexpressed in 90%of ureteral cancers and 84%of high-grade bladder cancers.Due to its high specificity,the NIR fluorescence sensor achieves the detection of FXYD3 in the range of 0.25-150 ng·ml^(-1)with a detection limit of 0.2 ng·ml^(-1).Importantly,it also can be used for accurate diagnosis of FXYD3 in the urine of patients with relevant cancers,and the results are consistent with clinical cystoscopy and pathological analysis.The proposed fluorescence sensor provides a simple,ultrasensitive,reliable method for UC screening,tumor-grade classification and postoperative monitoring and will have great potential for clinical applications.

一种以上转换和Fe_(3)O_(4)纳米粒子为基础的超灵敏ctDNA检测系统

ctDNA是重要的肿瘤标志物之一,在肿瘤疾病的早期诊断和临床监控方面发挥着重要作用.目前,常用的ct DNA检测方法通常都缺乏足够的灵敏性和特异性,不能满足实际诊疗的需要.因此,我们急需一种新型的、超灵敏的ct DNA检测方法.上转换纳米粒子是一种优异的发光材料,因其独特的发光特性在生物医学方面具有重要应用.因此,我们设计了一种以上转换和Fe_(3)O_(4)纳米粒子为基础的ct DNA检测方法.在该检测系统中,上转换和Fe_(3)O_(4)纳米粒子通过DNA碱基互补配对原则自组装在一起.目标序列可以通过熵驱动链置换(ESDR)反应将连着上转换纳米粒子的核酸链释放出来.经磁性分离后,上清液中上转换纳米粒子在980 nm激光器激发下的荧光强度与目标序列的浓度在1 nmol L^(-1)–100 amol L^(-1)的范围内具有非常好的线性关系,经计算,最低检出浓度为1.6 amol L^(-1).此外,该检测系统在识别单碱基突变、实际细胞和血清样本的检测中均有较好的应用.因此,该检测系统因为其灵敏性和特异性在肿瘤早期诊断、疾病进行过程监控、治疗方法评价和愈后风险评估等方面具有重大应用潜力.

Conducting polymer engineered covalent organic framework as a novel electrochemical amplifier for ultrasensitive detection of acetaminophen

Two-dimensional covalent organic framework(COF)has distinctive properties that offer potential opportunities for developing advanced electrode materials.In this work,a core-shell material composed of TAPB-DMTP-COF(TAPB,1,3,5-tris(4-aminophenyl)benzene;DMTP,2,5-dimethoxyterephaldehyde)core and conducting polymer shell,TAPB-DMTP-COF@PANI,was synthesized solvothermally using a polymerization method.The structural cha racteristics of the prepared composite were revealed by X-ray diffraction patterns(XRD),fourier transform infrared spectra(FTIR),X-ray photoelectron spectroscopy(XPS),transmission electron microscopy(TEM).The electrochemical analyses were verified by subsequent monitoring of trace levels of acetaminophen.This resultant composite not only facilitated acetaminophen to interact with absorption sites byπ-πstacking effect and hydrogen bonding but also overcame the poor conductivity of COF.Under the optimal conditions,a low limit of detection of 0.032μmol/L and wide linear range of 0.10-500μmol/L were obtained.The electrochemical platform was almost unaffected by other interfering substances,and successfully applied for the practical detection of acetaminophen in commercial tablet,human blood serum and urine.The enhanced performance makes this COF based core-shell composite a promising material in electrochemical senso r.

Ultrasensitive determination of intracellular hydrogen peroxide by equipping quantum dots with a sensing layer via self-passivation

Abnormal expression of hydrogen peroxide(H_(2)O_(2))indicates the disorder of cell functions and is able to induce the occurrence and deterioration of numerous diseases.However,limited by its low concentration under pathophysiological conditions,intracellular H_(2)O_(2) is still difficult to be determined to date.Herein,to achieve sensitive quantification of H_(2)O_(2) in cells,CIS/ZnS/ZnS quantum dots(CIS/d-ZnS QDs)are retrofitted with ZnO shells via self-passivation.Different from the traditional self-passivation of QDs,self-passivation of CIS/d-ZnS QDs is realized facilely without the assistance of additional cation ions,which improves optical properties of QDs and equips the QDs with a sensing layer.As a result,the CIS/d-ZnS/ZnO QDs exhibit enhanced fluorescence emission and stability.Relying on the decomposition of ZnO and ZnS shells in the presence of H_(2)O_(2),aggregated QDs reveal exciton energy transfer effect,resulting in fluorescence quenching.On a basis of this principle,a fluorescence H_(2)O_(2) sensor is further established with the CIS/d-ZnS/ZnO QDs.To be noted,since the equipped ZnO shells are more susceptible to H2O2 than original ZnS shells,analytical performance of the fluorescence sensor is remarkably promoted by the self-passivation of QDs.Accordingly,H_(2)O_(2) can be measured in 5 orders of magnitude with a limit of detection(LOD)of 0.46 nM.Furthermore,because the ZnO shells improve H2O2-responsive selectivity and sensitivity,variation of H_(2)O_(2) in cells can also be quantified with the CIS/d-ZnS/ZnO QDs.In this work,sensitive detection of intracellular H_(2)O_(2) is enabled by equipping QDs with a sensing layer,which provides an alternative perspective of functionalizing nanomaterials for analytical applications.

Ultrasensitive detection of IgE levels based on magnetic nanocapturer linked immunosensor assay for early diagnosis of cancer

Rapid and accurate detection of immunoglobulin E(Ig E) in serum and reduction of serum dosage are of great significance for clinical detection. Herein, we described a rapid magnetic separation of Ig E from patient serum based on Fe3 O4@Si O2-NTA@026 sdab as the capture probe and multiple horseradish peroxidase(HRP)-labeled antibodies linked gold nanoparticles(Au NPs) as chemiluminescence(CL) signal amplifier for ultrasensitive detection of total Ig E. Results showed that the limit of detection of our immunosensor system in serum samples was 0.03 k U/L, which is lowest in comparison with current methods, and far lower than that of Immuno CAP for Ig E detection(0.1 k U/L). Furthermore, our immunosensor possessed satisfied repeatability and accuracy, as well as good stability. In comparison with the Immuno CAP for the quantitative detection of Ig E, highly consistent results were achieved in 20 serum samples. Specially, this method was also successfully utilized for assessing the Ig E traces in breast cancer patients,which provides a new idea for the diagnosis of early cancer. Therefore, we believe that such versatile immunosensor will offer an alternative method for the on-site monitoring and determination of various Ig E-related diseases.

Ultrasensitive Label-free Detection of miRNA with Asymmetric Hairpin Probe, Exonuclease I and SYBR Green I

Detection of miRNAs presents a particular challenge because of their limited size, high sequence homo- logy and greatly various expression level. In this work, an ultrasensitive, label-free and isothermal miRNA detection was developed based on asymmertric hairpin probe, exonuclease I（Exo I） and SYBR Green I. The method employed asymmetric hairpin probe to perform cycled polymerization and Exo I to reduce background signal. In the presence of the target miRNA, the target triggers probe-mediated cycled polymerization reactions to generate lots of dsDNA products. The dsDNA product effectively prevents itself from being degraded by Exo I and permitted the insertion of more fluorescence dye into it to enlarge the fluorescence signal. In the absence of the target miRNA, there was no probe-mediated polymerization reaction, and the probe was digested by Exo I added, which minimized the intercala- tion of fluorescence dye to reduce the background signal. The combination of the probe-mediated cycled polymeriza- tion with the Exo 1-assisted background reduction allows us to achieve a detection limit of 5× 10^-18 mol/L. Owing to its ultrasensitivity, excellent specificity, convenience and low-cost, this method might hold out great promise in miRNA detection.

Supramolecular polymer materials based on pillar[5]arene:Ultrasensitive detection and efficient removal of cyanide

An ultrasensitive detection and effective removal material was successfully developed by using a pillar[n]arene-based supramolecular polymer gel(MTP5?HB).The MTP5?HB can ultrasensitively recognize Cu^2+and Fe^3+,and the limits of detection(LODs)for Cu^2+and Fe^3+are 1.55 and 2.68 nmol/L,respectively.Additionally,the in-situ generated metallogel MTP5?HB-Cu can exclusively detect CN,and the LOD for CN is 1.13 nmol/L.Noticeably,the xerogel of MTP5?HB-Cu can effectively remove CN from aqueous solution with 94.40%removal rate.Test kit based on MTP5?HB-Cu is also prepared for convenient detection of CN.

Asymmetric polymerase chain reaction and loop-mediated isothermal amplification(AP-LAMP) for ultrasensitive detection of microRNAs

In this manuscript,we first report an ultrasensitive detection assay of microRNA by combing asymmetric polymerase chain reaction(A-PCR)and loop-mediated isothermal amplification(LAMP)technology.Using A-PCR obtained an extended single strand to form LAMP stem-loop structure under isothermal amplification conditions.We used miRNAs as a loop primer probe in LAMP reaction and completed its ultrasensitive and rapid detection.The established method furnished a fast,specific and efficient detection of target miRNA with a detection limit as low as 10 amol/L in 90 min.