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.

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.

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.

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 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.

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,stretchable,and transparent humidity sensor based on ionconductive double-network hydrogel thin films

Ion-conductive hydrogels with intrinsic biocompatibility,stretchability,and stimuli-responsive capability have attracted considerable attention because of their extensive application potential in wearable sensing devices.The miniaturization and integration of hydrogel-based devices are currently expected to achieve breakthroughs in device performance and promote their practical application.However,currently,hydrogel film is rarely reported because it can be easily wrinkled,torn,and dehydrated,which severely hinders its development in microelectronics.Herein,thin,stretchable,and transparent ion-conductive double-network hydrogel films with controllable thickness are integrated with stretchable elastomer substrates,which show good environmental stability and ultrahigh sensitivity to humidity(78,785.5%/% relative humidity(RH)).Benefiting from the ultrahigh surface-area-to-volume ratio,abundant active sites,and short diffusion distance,the hydrogel film humidity sensor exhibits2×10^(5)times increased response to 98% RH,as well as 5.9 and7.6 times accelerated response and recovery speeds compared with the bulk counterpart,indicating its remarkable thicknessdependent humidity-sensing properties.The humidity-sensing mechanism reveals that the adsorption of water improves the ion migration and dielectric constant,as well as establishes the electrical double layer.Furthermore,the noncontact human-machine interaction and real-time respiratory frequency detection are enabled by the sensors.This work provides an innovative strategy to achieve further breakthroughs in device performance and promote the development of hydrogel-based miniaturized and integrated electronics.

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.

Entropy-driven strand displacement reaction for ultrasensitive detection of circulating tumor DNA based on upconversion and Fe_(3)O_(4) nanocrystals

Early detection of cancer biomarkers applied in real-time disease diagnosis and therapies can increase the survival rate of patients.Circulating tumor DNA(ct DNA)as a typical cancer biomarker plays a great role in the process of tumor disease monitoring,especially in early diagnosis.Unfortunately,most ct DNA detection systems have not been widely used due to their low sensitivity,poor specificity,and high cost.Herein,we developed an alternative ct DNA detection system to present the levels of ct DNA by recording the fluorescence signals of the system containing upconversion nanoparticles(UCNPs),Fe_(3)O_(4),and entropy-driven strand displacement reaction.The method has a practical sensitivity with a wide linear range from 100 amol L^(-1)to 1 nmol L^(-1)and a low detection limit of 1.6 amol L^(-1).Furthermore,the system demonstrates a practical application in mouse blood serum samples and meets the requirements for rapid,sensitive,specific,and economical diagnosis of cancers.Thus,this ct DNA detection system may have great potential for ct DNAdetection and clinical diagnosis.

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.

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.

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.

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.

Loss-induced phase transition in mid-infrared plasmonic metamaterials for ultrasensitive vibrational spectroscopy

Metamaterials have proven their ability to possess extraordinary physical properties distinct from naturally available materials,leading to exciting sensing functionalities and applications.However,metamaterial-based sensing applications suffer from severe performance limitations due to noise interference and design constraints.Here,we propose a dual-phase strategy that leverages loss-induced different Fano-resonant phases to access both destructive and constructive signals of molecular vibration.When the two reverse signals are innovatively combined,the noise in the detection system is effectively suppressed,thereby breaking through the noise-related limitations.Additionally,by utilizing loss optimization of the plasmon-molecule coupling system,our dual-phase strategy enhances the efficiency of infrared energy transfer into the molecule without any additional fabrication complex,thereby overcoming the trade-off dilemma between performance and fabrication cost.Thanks to the pioneering breakthroughs in the limitations,our dual-phase strategy possesses an overwhelming competitive advantage in ultrasensitive vibrational spectroscopy over traditional metamaterial technology,including strong signal strength(×4),high sensitivity(×4.2),effective noise suppression(30%),low detection limit(13 ppm),and excellent selectivity among CO_(2),NH_(3),and CH_(4) mixtures.This work not only opens the door to various emerging ultrasensitive detection applications,including ultrasensitive in-breath diagnostics and high-information analysis of molecular information in dynamic reactions,but also gains new insights into the plasmon-molecule interactions in advanced metamaterials.

Structural basis of the ultrasensitive calcium indicator GCaMP6

GCaMP is one of the most widely used calcium indicators in neuronal imaging and calcium cell biology. The newly developed GCaMP6 shows superior brightness and ultrasensitivity to calcium concentration change. In this study, we determined crystal structures of CaZ＋-bound GCaMP6 monomer and dimer and presented detailed structural analyses in comparison with its par- ent version GCaMP5G. Our analyses reveal the structural basis for the outperformance of this newly developed Ca2＋ indicator. Three substitution mutations and the resulting changes of local structure and interaction explain the ultrasensitivity and in- creased fluorescence intensity common to all three versions of GCaMP6. Each particular substitution in the three GCaMP6 is also structurally consistent with their differential sensitivity and intensity, maximizing the potential of using GCaMP6 in solving diverse problems in neuronal research and calcium signaling. Our studies shall also be beneficial to further structure-guided optimization of GCaMP and facilitate the design of novel calcium indicators.

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.