Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue b...Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue bioimaging and non-invasive biodetection,owing to their superior advantages including good photochemical stability,sharp emission peaks,large penetration depth,and high signal-to-noise ratio[1].Conventionally,Yb3t-and Nd3t-sensitized NCs have been utilized as NIR-II luminescent nanoprobes for in vivo bioimaging upon excitation with 980 and 808 nm diode laser,respectively[2].展开更多
Recent advancements in artificial intelligence have transformed three-dimensional(3D)optical imaging and metrology,enabling high-resolution and high-precision 3D surface geometry measurements from one single fringe pa...Recent advancements in artificial intelligence have transformed three-dimensional(3D)optical imaging and metrology,enabling high-resolution and high-precision 3D surface geometry measurements from one single fringe pattern projection.However,the imaging speed of conventional fringe projection profilometry(FPP)remains limited by the native sensor refresh rates due to the inherent"one-to-one"synchronization mechanism between pattern projection and image acquisition in standard structured light techniques.Here,we present dual-frequency angular-multiplexed fringe projection profilometry(DFAMFPP),a deep learning-enabled 3D imaging technique that achieves high-speed,high-precision,and large-depth-range absolute 3D surface measurements at speeds 16 times faster than the sensor's native frame rate.By encoding multi-timeframe 3D information into a single multiplexed image using multiple pairs of dual-frequency fringes,high-accuracy absolute phase maps are reconstructed using specially trained two-stage number-theoretical-based deep neural networks.We validate the effectiveness of DFAMFPP through dynamic scene measurements,achieving 10,000 Hz 3D imaging of a running turbofan engine prototype with only a 625 Hz camera.By overcoming the sensor hardware bottleneck,DFAMFPP significantly advances high-speed and ultra-high-speed 3D imaging,opening new avenues for exploring dynamic processes across diverse scientific disciplines.展开更多
CRISPR homing gene drives have considerable potential for managing populations of medically and agriculturally significant insects.They operate by Cas9 cleavage followed by homology-directed repair,copying the drive a...CRISPR homing gene drives have considerable potential for managing populations of medically and agriculturally significant insects.They operate by Cas9 cleavage followed by homology-directed repair,copying the drive allele to the wild-type chromosome and thus increasing in frequency and spreading throughout a population.However,resistance alleles formed by end-joining repair pose a significant obstacle.To address this,we create a homing drive targeting the essential hairy gene in Drosophila melanogaster.Nonfunctional resistance alleles are recessive lethal,while drive carriers have a recoded“rescue”version of hairy.The drive inheritance rate is moderate,and multigenerational cage studies show drive spread to 96%–97%of the population.However,the drive does not reach 100%due to the formation of functional resistance alleles despite using four gRNAs.These alleles have a large deletion but likely utilize an alternate start codon.Thus,revised designs targeting more essential regions of a gene may be necessary to avoid such functional resistance.Replacement of the rescue element’s native 3'UTR with a homolog from another species increases drive inheritance by 13%–24%.This was possibly because of reduced homology between the rescue element and surrounding genomic DNA,which could also be an important design consideration for rescue gene drives.展开更多
Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in bio...Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in biological subjects.Current semi-implantable devices are mainly based on single-parameter detection.Miniaturized semi-implantable electrodes for multiparameter sensing have more restrictions on the electrode size due to biocompatibility considerations,but reducing the electrode surface area could potentially limit electrode sensitivity.This study developed a semi-implantable device system comprising a multiplexed microfilament electrode cluster(MMEC)and a printed circuit board for real-time monitoring of intra-tissue K^(+),Ca^(2+),and Na^(+)concentrations.The electrode surface area was less important for the potentiometric sensing mechanism,suggesting the feasibility of using a tiny fiber-like electrode for potentiometric sensing.The MMEC device exhibited a broad linear response(K^(+):2–32 mmol/L;Ca^(2+):0.5–4 mmol/L;Na^(+):10–160 mmol/L),high sensitivity(about 20–45 mV/decade),temporal stability(>2weeks),and good selectivity(>80%)for the above ions.In vitro detection and in vivo subcutaneous and brain experiment results showed that the MMEC system exhibits good multi-ion monitoring performance in several complex environments.This work provides a platform for the continuous real-time monitoring of ion fluctuations in different situations and has implications for developing smart sensors to monitor human health.展开更多
Laser absorption spectroscopy has proven to be an effective approach for gas sensing, which plays an important rolein the fields of military, industry, medicine and basic research. This paper presents a multiplexed ga...Laser absorption spectroscopy has proven to be an effective approach for gas sensing, which plays an important rolein the fields of military, industry, medicine and basic research. This paper presents a multiplexed gas sensing system basedon optical frequency comb (OFC) calibrated frequency-modulated continuous-wave (FMCW) tuning nonlinearity. Thesystem can be used for multi-parameter synchronous measurement of gas absorption spectrum and multiplexed opticalpath. Multi-channel parallel detection is realized by combining wavelength division multiplexing (WDM) and frequencydivision multiplexing (FDM) techniques. By introducing nonlinear optical crystals, broadband spectrum detection is simultaneouslyachieved over a bandwidth of hundreds of nanometers. An OFC with ultra-high frequency stability is used asthe frequency calibration source, which guarantees the measurement accuracy. The test samples involve H13C14N, C_(2)H_(2)and Rb vapor cells of varying densities and 5 parallel measurement experiments are designed. The results show that themeasurement accuracies of spectral absorption line and the optical path are 150 MHz and 20 m, respectively. The schemeoffers the advantages of multiplexed, multi-parameter, wide spectrum and high resolution detection, which can realize theidentification of multi-gas components and the high-precision inversion of absorption lines under different environments.The proposed sensor demonstrates great potential in the field of high-resolution absorption spectrum measurement for gassensing applications.展开更多
Fluorescently encoded microbeads are in demand for multiplexed applications in different fields.Compared to organic dye-based commercially available Luminex's x MAP technology, upconversion nanoparticles(UCNPs) ar...Fluorescently encoded microbeads are in demand for multiplexed applications in different fields.Compared to organic dye-based commercially available Luminex's x MAP technology, upconversion nanoparticles(UCNPs) are better alternatives due to their large antiStokes shift, photostability, nil background, and single wavelength excitation. Here, we developed a new multiplexed detection system using UCNPs for encoding poly(ethylene glycol) diacrylate(PEGDA) microbeads as well as for labeling reporter antibody. However, to prepare UCNPs-encoded microbeads, currently used swellingbased encapsulation leads to non-uniformity, which is undesirable for fluorescence-based multiplexing. Hence,we utilized droplet microfluidics to obtain encoded microbeads of uniform size, shape, and UCNPs distribution inside. Additionally, PEGDA microbeads lack functionality for probe antibodies conjugation on their surface.Methods to functionalize the surface of PEGDA microbeads(acrylic acid incorporation, polydopamine coating)reported thus far quench the fluorescence of UCNPs. Here,PEGDA microbeads surface was coated with silica followed by carboxyl modification without compromising the fluorescence intensity of UCNPs. In this study, droplet microfluidics-assisted UCNPs-encoded microbeads of uniform shape, size, and fluorescence were prepared.Multiple color codes were generated by mixing UCNPs emitting red and green colors at different ratios prior to encapsulation. UCNPs emitting blue color were used to label the reporter antibody. Probe antibodies were covalently immobilized on red UCNPs-encoded microbeads for specific capture of human serum albumin(HSA) as a model protein. The system was also demonstrated for multiplexed detection of both human C-reactive protein(hCRP) and HSA protein by immobilizing anti-h CRP antibodies on green UCNPs.展开更多
Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid biopsy.Because of their nanoscale size,complex biogenesis,and met...Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid biopsy.Because of their nanoscale size,complex biogenesis,and methodological limitations related to exosome isolation and detection,advancements in their analysis remain slow.Microfluidic technology offers a better analytic approach compared with conventional methods.Here,we developed a bead-based microarray for exosome isolation and multiplexed tumor marker detection.Using this method,exosomes are isolated by binding to antibodies on the bead surface,and tumor markers on the exosomes are detected through quantum dot(QD)probes.The beads are then uniformly trapped and queued among micropillars in the chip.This design benefits fluorescence observation by dispersing the signals into every single bead,thereby avoiding optical interference and enabling more accurate test results.We analyzed exosomes in the cell culture supernatant of lung cancer and endothelial cell lines,and different lung cancer markers labeled with three QD probes were used to conduct multiplexed detection of exosome surface protein markers.Lung cancer-derived samples showed much higher(~sixfold-tenfold)fluorescence intensity than endothelial cell samples,and different types of lung cancer samples showed distinctive marker expression levels.Additionally,using the chip to detect clinical plasma samples from cancer patients showed good diagnostic power and revealed a well consistency with conventional tests for serological markers.These results provide insight into a promising method for exosome tumor marker detection and early-stage cancer diagnosis.展开更多
Extracellular vesicles(EVs)are cell-derived membranous particles that play a crucial role in molecular trafficking,intercellular transport and the egress of unwanted proteins.They have been implicated in many diseases...Extracellular vesicles(EVs)are cell-derived membranous particles that play a crucial role in molecular trafficking,intercellular transport and the egress of unwanted proteins.They have been implicated in many diseases including cancer and neurodegeneration.EVs are detected in all bodily fluids,and their protein and nucleic acid content offers a means of assessing the status of the cells from which they originated.As such,they provide opportunities in biomarker discovery for diagnosis,prognosis or the stratification of diseases as well as an objective monitoring of therapies.The simultaneous assaying of multiple EV-derived markers will be required for an impactful practical application,and multiplexing platforms have evolved with the potential to achieve this.Herein,we provide a comprehensive overview of the currently available multiplexing platforms for EV analysis,with a primary focus on miniaturized and integrated devices that offer potential step changes in analytical power,throughput and consistency.展开更多
Multiplexed immunohistochemistry/fluorescence(mIHC/IF)in combination with multispectral unmixing is a novel multitarget histopathological staining and imaging technique.By simultaneously revealing expression level and...Multiplexed immunohistochemistry/fluorescence(mIHC/IF)in combination with multispectral unmixing is a novel multitarget histopathological staining and imaging technique.By simultaneously revealing expression level and spatial information for up to eight biomarkers in situ,in addition to a nuclear stain within a single formalin-fixed paraffin-embedded(FFPE)tissue section,this technology can analyze the phenotype,abundance,morphology and intercellular relationship of cells while providing statistically significant results.In recent years,technical improvements have brought new insight into mIHC/IF and multispectral imaging approaches,which have been successfully applied in the field of cancer immunotherapy,specifically in regard to tumor microenvironment research,immunotherapy drug discovery,and prognostic and metastatic risk evaluation.This review highlights the principle,workflow,advantages and disadvantages of the technology,and discusses the latest applications of mIHC/IF-based imaging technology in the field of TME-related research and immunotherapy drug discovery.展开更多
To study the selective erasure and rewriting of the multiplexed holographic storage inphotorefractive crystals.According to the mechanism on forming of phase hologram in photore-fractive crystal,by incoherently additi...To study the selective erasure and rewriting of the multiplexed holographic storage inphotorefractive crystals.According to the mechanism on forming of phase hologram in photore-fractive crystal,by incoherently addition of the complementary hologram and the original holo-gram,the selective erasure and rewriting were accomplished.The complementary holography isan effective and convenient technique for selective erasure and rewriting of multiplexed holo-graphic storage in photorefractive crystals.展开更多
Optical orbital angular momentum(OAM)multiplexed holography has been implemented as an effective method for information encryption and storage.Multiramp helicoconical-OAM multiplexed holography is proposed and experim...Optical orbital angular momentum(OAM)multiplexed holography has been implemented as an effective method for information encryption and storage.Multiramp helicoconical-OAM multiplexed holography is proposed and experimentally implemented.The mode selectivity of the multiramp mixed screw-edge dislocations,constant parameter K,and normalized factor are investigated,respectively,which demonstrates that those parameters can be used as additional coding degrees of freedom for holographic multiplexing.The combination of the topological charge and the other three parameters can provide a four-dimensional multiplexed holography and can enhance information capacity.展开更多
This paper presents the fundamental technique of phase generated carrier （PGC） and its realization on compact reconfigurable input and output （RIO） which adopts real-time and field programmable grate array （FPGA...This paper presents the fundamental technique of phase generated carrier （PGC） and its realization on compact reconfigurable input and output （RIO） which adopts real-time and field programmable grate array （FPGA） techniques. Improvement of the PGC technique is also introduced by using peak-to-peak value detection method to reduce the influence of variation of the light intensity. A four-element fibre Bragg gratings （FBG） laser sensor system is conducted in the experiment and the demodulated results demonstrate correlation coefficient as high as 0.995 with the reference signal and the dynamic range to be 120dB@63Hz.展开更多
Efforts have been made to establish various human pluripotent stem cell lines.However,such methods have not yet been duplicated in non-human primate cells.Here,we introduce a multiplexed single-cell sequencing techniq...Efforts have been made to establish various human pluripotent stem cell lines.However,such methods have not yet been duplicated in non-human primate cells.Here,we introduce a multiplexed single-cell sequencing technique to profile the molecular features of monkey pluripotent stem cells in published culture conditions.The results demonstrate suboptimized maintenance of pluripotency and show that the selected signaling pathways for resetting human stem cells can also be interpreted for establishing monkey cell lines.Overall,this work legitimates the translation of novel human cell line culture conditions to monkey cells and provides guidance for exploring chemical cocktails for monkey stem cell line derivation.展开更多
Monitoring multiplexed biochemical markers is beneficial for the comprehensive evaluation of diabetes-associated complications.Techniques for multiplexed analyses in interstitial fluids have often been restricted by t...Monitoring multiplexed biochemical markers is beneficial for the comprehensive evaluation of diabetes-associated complications.Techniques for multiplexed analyses in interstitial fluids have often been restricted by the difficulties of electrode materials in accurately detecting chemicals in complex subcutaneous spaces.In particular,the signal stability of enzyme-based sensing electrodes often inevitably decreases due to enzyme degradation or interference in vivo.In this study,we developed a self-calibrating multiplexed microneedle(MN)electrode array(SC-MMNEA)capable of continuous,real-time monitoring of multiple types of bioanalytes(glucose,cholesterol,uric acid,lactate,reactive oxygen species[ROSs],Na+,K+,Ca2+,and pH)in the subcutaneous space.Each type of analyte was detected by a discrete MN electrode assembled in an integrated array with single-MN resolution.Moreover,this device utilized an MN-delivery-mediated self-calibration technique to address the inherent problem of decreased accuracy of implantable electrodes caused by long-term tissue variation and enzyme degradation,and this technique might increase the reliability of the MN sensors.Our results indicated that SC-MMNEA could provide real-time monitoring of multiplexed analyte concentrations in a rat model with good accuracy,especially after self-calibration.SC-MMNEA has the advantages of in situ and minimally invasive monitoring of physiological states and the potential to promote wearable devices for long-term monitoring of chemical species in vivo.展开更多
A laser sensing system based on beat frequency demodulation is proposed. The sensor uses a single-longitudinal-mode distributed Bragg reflector （DBR） fiber laser as a sensing element. This laser sensor has great mul...A laser sensing system based on beat frequency demodulation is proposed. The sensor uses a single-longitudinal-mode distributed Bragg reflector （DBR） fiber laser as a sensing element. This laser sensor has great multiplexing capability due to its wide free spectral range. Wavelength-division-multiplex （WDM） and frequency-division-multiplex （FDM） techniques are studied. The sensing system has high sensitivity and multiplexing channels.展开更多
Nanocrossbar is a potential memory architecture to integrate memristor to achieve large scale and high density mem- ory. However, based on the currently widely-adopted parallel reading scheme, scalability of the nanoc...Nanocrossbar is a potential memory architecture to integrate memristor to achieve large scale and high density mem- ory. However, based on the currently widely-adopted parallel reading scheme, scalability of the nanocrossbar memory is limited, since the overhead of the reading circuits is in proportion with the size of the nanocrossbar component. In this paper, a multiplexed reading scheme is adopted as the foundation of the discussion. Through HSPICE simulation, we reanalyze scalability of the nanocrossbar memristor memory by investigating the impact of various circuit parameters on the output voltage swing as the memory scales to larger size. We find that multiplexed reading maintains sufficient noise margin in large size nanocrossbar memristor memory. In order to improve the scalability of the memory, memristors with nonlinear I-V characteristics and high LRS （low resistive state） resistance should be adopted.展开更多
Development and testing of a serially multiplexed fiber optic sensor system is described.The sensor differs from conventional fiber optic acoustic systems,as it is capable of sensing AE emissions at several points alo...Development and testing of a serially multiplexed fiber optic sensor system is described.The sensor differs from conventional fiber optic acoustic systems,as it is capable of sensing AE emissions at several points along the length of a single fiber.Multiplexing provides for single channel detection of cracks and their locations in large structural systems. An algorithm was developed for signal recognition and tagging of the AE waveforms for detection of' crack locations,Labora- tory experiments on plain concrete beams and post-tensioned FRP tendons were pcrlormed to evaluate the crack detection capability of the sensor system.The acoustic emission sensor was able to detect initiation,growth and location of the cracks in concrete as well as in the FRP tendons.The AE system is potentially suitable lot applications involving health monitoring of structures following an earthquake.展开更多
During the last decades the whispering gallery mode based sensors have become a prominent solution for label-free sensing of various physical and chemical parameters.At the same time,the widespread utilization of the ...During the last decades the whispering gallery mode based sensors have become a prominent solution for label-free sensing of various physical and chemical parameters.At the same time,the widespread utilization of the approach is hindered by the restricted applicability of the known configurations for ambient variations quantification outside the laboratory conditions and their low affordability,where necessity on the spectrally-resolved data collection is among the main limiting factors.In this paper we demonstrate the first realization of an affordable whispering gallery mode sensor powered by deep learning and multi-resonator imaging at a fixed frequency.It has been shown that the approach enables refractive index unit(RIU)prediction with an absolute error at 3×10^(-6) level for dynamic range of the RIU variations from 0 to 2×10^(-3) with temporal resolution of several milliseconds and instrument-driven detection limit of 3×10−5.High sensing accuracy together with instrumental affordability and production simplicity places the reported detector among the most cost-effective realizations of the whispering gallery mode approach.The proposed solution is expected to have a great impact on the shift of the whole sensing paradigm away from the model-based and to the flexible self-learning solutions.展开更多
Atmospheric turbulence（AT） induced crosstalk can significantly impair the performance of a free-space optical（FSO）communication link using orbital angular momentum（OAM） multiplexing.In this paper,we propose a mu...Atmospheric turbulence（AT） induced crosstalk can significantly impair the performance of a free-space optical（FSO）communication link using orbital angular momentum（OAM） multiplexing.In this paper,we propose a multiple-user detection（MUD） turbulence mitigation scheme in an OAM-multiplexed FSO communication link.First,we present a MUD equivalent communication model for an OAM-multiplexed FSO communication link under AT.In the equivalent model,each input bit stream represents one user＇s information.The deformed OAM spatial modes caused by AT,instead of the pure OAM spatial modes,are used as information carriers,and the overlapping between the deformed OAM spatial modes are computed as the correlation coefficients between the users.Then,we present a turbulence mitigation scheme based on MUD idea to enhance AT tolerance of the OAM-multiplexed FSO communication link.In the proposed scheme,the crosstalk caused by AT is used as a useful component to deduce users＇ information.The numerical results show that the performance of the OAM-multiplexed communication link has greatly improved by the proposed scheme.When the turbulence strength C_n^2 is 1 × 10^（-15） m^（-2/3）,the transmission distance is 1000 m and the channel signal-to-noise ratio（SNR）is 26 dB,the bit-error-rate（BER） performance of four spatial multiplexed OAM modes l_m = ＋ 1,＋2,＋3,＋4 are all close to 10-5,and there is a 2-3 fold increase in the BER performance in comparison with those results without the proposed scheme.In addition,the proposed scheme is more effective for an OAM-multiplexed FSO communication link with a larger OAM mode topological charge interval.The proposed scheme is a promising direction for compensating the interference caused by AT in the OAM-multiplexed FSO communication link.展开更多
In this paper, we experimentally investigate the dark diffusional enhancement of the optimized multiplexed grating in the phenanthrenequinone doped poly （methyl methacrylate） （PQ-PMMA） photopolymer. The possibilit...In this paper, we experimentally investigate the dark diffusional enhancement of the optimized multiplexed grating in the phenanthrenequinone doped poly （methyl methacrylate） （PQ-PMMA） photopolymer. The possibility of improving the holographic characteristics of the material through the dark enhancement is demonstrated. The optimal preillumination exposure and the optimal time interval between exposures are extracted to obtain the optimized diffraction efficiency, and their values are 3.4×103 mJ/cm2 and 2 min, respectively. The dark enhancement of the multiplexed grating is presented as an effective method to improve the response region and the dynamic range and to prevent saturation of the material. The dependence of the phenanthrenequinone concentration on the increment of the refractive index modulation is quantitatively studied, which provides a significant basis for improving the homogeneity in the multiplexed gratings using a quantitative strategy. Finally, a simple experimental procedure using the dark enhancement is introduced to improve the homogeneity of the diffraction efficiency and to avoid the complex schedule exposure.展开更多
基金supported by the National Natural Science Foundation of China(Nos.12474418,U22A20398,and 22135008).
文摘Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue bioimaging and non-invasive biodetection,owing to their superior advantages including good photochemical stability,sharp emission peaks,large penetration depth,and high signal-to-noise ratio[1].Conventionally,Yb3t-and Nd3t-sensitized NCs have been utilized as NIR-II luminescent nanoprobes for in vivo bioimaging upon excitation with 980 and 808 nm diode laser,respectively[2].
基金supported by National Key Research and Development Program of China(2022YFB2804603,2022YFB2804605)National Natural Science Foundation of China(U21B2033)+4 种基金Fundamental Research Funds forthe Central Universities(2023102001,2024202002)National Key Laborato-ry of Shock Wave and Detonation Physics(JCKYS2024212111)China Post-doctoral Science Fund(2023T160318)Open Research Fund of JiangsuKey Laboratory of Spectral Imaging&Intelligent Sense(JSGP202105,JSGP202201)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX25_0695,SJCX25_0188)。
文摘Recent advancements in artificial intelligence have transformed three-dimensional(3D)optical imaging and metrology,enabling high-resolution and high-precision 3D surface geometry measurements from one single fringe pattern projection.However,the imaging speed of conventional fringe projection profilometry(FPP)remains limited by the native sensor refresh rates due to the inherent"one-to-one"synchronization mechanism between pattern projection and image acquisition in standard structured light techniques.Here,we present dual-frequency angular-multiplexed fringe projection profilometry(DFAMFPP),a deep learning-enabled 3D imaging technique that achieves high-speed,high-precision,and large-depth-range absolute 3D surface measurements at speeds 16 times faster than the sensor's native frame rate.By encoding multi-timeframe 3D information into a single multiplexed image using multiple pairs of dual-frequency fringes,high-accuracy absolute phase maps are reconstructed using specially trained two-stage number-theoretical-based deep neural networks.We validate the effectiveness of DFAMFPP through dynamic scene measurements,achieving 10,000 Hz 3D imaging of a running turbofan engine prototype with only a 625 Hz camera.By overcoming the sensor hardware bottleneck,DFAMFPP significantly advances high-speed and ultra-high-speed 3D imaging,opening new avenues for exploring dynamic processes across diverse scientific disciplines.
基金supported by laboratory startup funds from Peking University and the Center for Life Sciences,as well as the grants from the National Science Foundation of China(32302455 and 32270672)。
文摘CRISPR homing gene drives have considerable potential for managing populations of medically and agriculturally significant insects.They operate by Cas9 cleavage followed by homology-directed repair,copying the drive allele to the wild-type chromosome and thus increasing in frequency and spreading throughout a population.However,resistance alleles formed by end-joining repair pose a significant obstacle.To address this,we create a homing drive targeting the essential hairy gene in Drosophila melanogaster.Nonfunctional resistance alleles are recessive lethal,while drive carriers have a recoded“rescue”version of hairy.The drive inheritance rate is moderate,and multigenerational cage studies show drive spread to 96%–97%of the population.However,the drive does not reach 100%due to the formation of functional resistance alleles despite using four gRNAs.These alleles have a large deletion but likely utilize an alternate start codon.Thus,revised designs targeting more essential regions of a gene may be necessary to avoid such functional resistance.Replacement of the rescue element’s native 3'UTR with a homolog from another species increases drive inheritance by 13%–24%.This was possibly because of reduced homology between the rescue element and surrounding genomic DNA,which could also be an important design consideration for rescue gene drives.
基金The authors would like to acknowledge financial support from the National Key R&D Program of China(Nos.2021YFF1200700 and 2021YFA0911100)the National Natural Science Foundation of China(Nos.T2225010,32171399,and 32171456)+4 种基金the Fundamental Research Funds for the Central Universities,Sun Yat-Sen University(No.22dfx02)Pazhou Lab,Guangzhou(No.PZL2021KF0003)The authors also would like to thank the funding support from the Opening Project of Key Laboratory of Microelectronic Devices&Integrated Technology,Institute of Microelectronics,Chinese Academy of Sciences,and State Key Laboratory of Precision Measuring Technology and Instruments(No.pilab2211)QQOY would like to thank the China Postdoctoral Science Foundation(No.2022M713645)JL would like to thank the National Natural Science Foundation of China(No.62105380)and the China Postdoctoral Science Foundation(No.2021M693686).
文摘Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in biological subjects.Current semi-implantable devices are mainly based on single-parameter detection.Miniaturized semi-implantable electrodes for multiparameter sensing have more restrictions on the electrode size due to biocompatibility considerations,but reducing the electrode surface area could potentially limit electrode sensitivity.This study developed a semi-implantable device system comprising a multiplexed microfilament electrode cluster(MMEC)and a printed circuit board for real-time monitoring of intra-tissue K^(+),Ca^(2+),and Na^(+)concentrations.The electrode surface area was less important for the potentiometric sensing mechanism,suggesting the feasibility of using a tiny fiber-like electrode for potentiometric sensing.The MMEC device exhibited a broad linear response(K^(+):2–32 mmol/L;Ca^(2+):0.5–4 mmol/L;Na^(+):10–160 mmol/L),high sensitivity(about 20–45 mV/decade),temporal stability(>2weeks),and good selectivity(>80%)for the above ions.In vitro detection and in vivo subcutaneous and brain experiment results showed that the MMEC system exhibits good multi-ion monitoring performance in several complex environments.This work provides a platform for the continuous real-time monitoring of ion fluctuations in different situations and has implications for developing smart sensors to monitor human health.
基金the National Natural Science Foun-dation of China(Grant No.52375546)the National Key Research and Development Program of China(Grant No.2022YFF0705701).
文摘Laser absorption spectroscopy has proven to be an effective approach for gas sensing, which plays an important rolein the fields of military, industry, medicine and basic research. This paper presents a multiplexed gas sensing system basedon optical frequency comb (OFC) calibrated frequency-modulated continuous-wave (FMCW) tuning nonlinearity. Thesystem can be used for multi-parameter synchronous measurement of gas absorption spectrum and multiplexed opticalpath. Multi-channel parallel detection is realized by combining wavelength division multiplexing (WDM) and frequencydivision multiplexing (FDM) techniques. By introducing nonlinear optical crystals, broadband spectrum detection is simultaneouslyachieved over a bandwidth of hundreds of nanometers. An OFC with ultra-high frequency stability is used asthe frequency calibration source, which guarantees the measurement accuracy. The test samples involve H13C14N, C_(2)H_(2)and Rb vapor cells of varying densities and 5 parallel measurement experiments are designed. The results show that themeasurement accuracies of spectral absorption line and the optical path are 150 MHz and 20 m, respectively. The schemeoffers the advantages of multiplexed, multi-parameter, wide spectrum and high resolution detection, which can realize theidentification of multi-gas components and the high-precision inversion of absorption lines under different environments.The proposed sensor demonstrates great potential in the field of high-resolution absorption spectrum measurement for gassensing applications.
基金the funding support from the Singapore Ministry of Education Academic Research Fund (AcRF Tier 3 Grant MOE2016-T3-1-004, R-397-000274-112 AcRF Tier 1 Grant R-397-000-270-114)
文摘Fluorescently encoded microbeads are in demand for multiplexed applications in different fields.Compared to organic dye-based commercially available Luminex's x MAP technology, upconversion nanoparticles(UCNPs) are better alternatives due to their large antiStokes shift, photostability, nil background, and single wavelength excitation. Here, we developed a new multiplexed detection system using UCNPs for encoding poly(ethylene glycol) diacrylate(PEGDA) microbeads as well as for labeling reporter antibody. However, to prepare UCNPs-encoded microbeads, currently used swellingbased encapsulation leads to non-uniformity, which is undesirable for fluorescence-based multiplexing. Hence,we utilized droplet microfluidics to obtain encoded microbeads of uniform size, shape, and UCNPs distribution inside. Additionally, PEGDA microbeads lack functionality for probe antibodies conjugation on their surface.Methods to functionalize the surface of PEGDA microbeads(acrylic acid incorporation, polydopamine coating)reported thus far quench the fluorescence of UCNPs. Here,PEGDA microbeads surface was coated with silica followed by carboxyl modification without compromising the fluorescence intensity of UCNPs. In this study, droplet microfluidics-assisted UCNPs-encoded microbeads of uniform shape, size, and fluorescence were prepared.Multiple color codes were generated by mixing UCNPs emitting red and green colors at different ratios prior to encapsulation. UCNPs emitting blue color were used to label the reporter antibody. Probe antibodies were covalently immobilized on red UCNPs-encoded microbeads for specific capture of human serum albumin(HSA) as a model protein. The system was also demonstrated for multiplexed detection of both human C-reactive protein(hCRP) and HSA protein by immobilizing anti-h CRP antibodies on green UCNPs.
基金supported by Grants from National Key Research and Development Program of China(Nos.2018YFA0108202 and 2017YFA0205300)National Science Foundation of China(Nos.61571429,61571077,61801464,and 61801465)+1 种基金the STS Project of the Chinese Academy of Sciences(No.KFJ-STS-SCYD-120)the Science and Technology Commission of Shanghai Municipality(Nos.16410711800 and 4391901900).
文摘Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid biopsy.Because of their nanoscale size,complex biogenesis,and methodological limitations related to exosome isolation and detection,advancements in their analysis remain slow.Microfluidic technology offers a better analytic approach compared with conventional methods.Here,we developed a bead-based microarray for exosome isolation and multiplexed tumor marker detection.Using this method,exosomes are isolated by binding to antibodies on the bead surface,and tumor markers on the exosomes are detected through quantum dot(QD)probes.The beads are then uniformly trapped and queued among micropillars in the chip.This design benefits fluorescence observation by dispersing the signals into every single bead,thereby avoiding optical interference and enabling more accurate test results.We analyzed exosomes in the cell culture supernatant of lung cancer and endothelial cell lines,and different lung cancer markers labeled with three QD probes were used to conduct multiplexed detection of exosome surface protein markers.Lung cancer-derived samples showed much higher(~sixfold-tenfold)fluorescence intensity than endothelial cell samples,and different types of lung cancer samples showed distinctive marker expression levels.Additionally,using the chip to detect clinical plasma samples from cancer patients showed good diagnostic power and revealed a well consistency with conventional tests for serological markers.These results provide insight into a promising method for exosome tumor marker detection and early-stage cancer diagnosis.
基金funded by grants from the EPSRC(EP/M006204/1)the Michael J Fox Foundation+2 种基金the Selfridges Group Foundationthe NIHR Oxford Biomedical Research Centre to G.K.T and J.J.Dsupport from the John Fell Fund(HMD00470).
文摘Extracellular vesicles(EVs)are cell-derived membranous particles that play a crucial role in molecular trafficking,intercellular transport and the egress of unwanted proteins.They have been implicated in many diseases including cancer and neurodegeneration.EVs are detected in all bodily fluids,and their protein and nucleic acid content offers a means of assessing the status of the cells from which they originated.As such,they provide opportunities in biomarker discovery for diagnosis,prognosis or the stratification of diseases as well as an objective monitoring of therapies.The simultaneous assaying of multiple EV-derived markers will be required for an impactful practical application,and multiplexing platforms have evolved with the potential to achieve this.Herein,we provide a comprehensive overview of the currently available multiplexing platforms for EV analysis,with a primary focus on miniaturized and integrated devices that offer potential step changes in analytical power,throughput and consistency.
基金supported by State Key Laboratory of Natural and Biomimetic Drugs,Peking University。
文摘Multiplexed immunohistochemistry/fluorescence(mIHC/IF)in combination with multispectral unmixing is a novel multitarget histopathological staining and imaging technique.By simultaneously revealing expression level and spatial information for up to eight biomarkers in situ,in addition to a nuclear stain within a single formalin-fixed paraffin-embedded(FFPE)tissue section,this technology can analyze the phenotype,abundance,morphology and intercellular relationship of cells while providing statistically significant results.In recent years,technical improvements have brought new insight into mIHC/IF and multispectral imaging approaches,which have been successfully applied in the field of cancer immunotherapy,specifically in regard to tumor microenvironment research,immunotherapy drug discovery,and prognostic and metastatic risk evaluation.This review highlights the principle,workflow,advantages and disadvantages of the technology,and discusses the latest applications of mIHC/IF-based imaging technology in the field of TME-related research and immunotherapy drug discovery.
文摘To study the selective erasure and rewriting of the multiplexed holographic storage inphotorefractive crystals.According to the mechanism on forming of phase hologram in photore-fractive crystal,by incoherently addition of the complementary hologram and the original holo-gram,the selective erasure and rewriting were accomplished.The complementary holography isan effective and convenient technique for selective erasure and rewriting of multiplexed holo-graphic storage in photorefractive crystals.
基金supported by the National Natural Science Foundation of China(Grant No.61775153)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Optical orbital angular momentum(OAM)multiplexed holography has been implemented as an effective method for information encryption and storage.Multiramp helicoconical-OAM multiplexed holography is proposed and experimentally implemented.The mode selectivity of the multiramp mixed screw-edge dislocations,constant parameter K,and normalized factor are investigated,respectively,which demonstrates that those parameters can be used as additional coding degrees of freedom for holographic multiplexing.The combination of the topological charge and the other three parameters can provide a four-dimensional multiplexed holography and can enhance information capacity.
基金supported by the National 863 Program under Grant No 2007AA03Z415.
文摘This paper presents the fundamental technique of phase generated carrier （PGC） and its realization on compact reconfigurable input and output （RIO） which adopts real-time and field programmable grate array （FPGA） techniques. Improvement of the PGC technique is also introduced by using peak-to-peak value detection method to reduce the influence of variation of the light intensity. A four-element fibre Bragg gratings （FBG） laser sensor system is conducted in the experiment and the demodulated results demonstrate correlation coefficient as high as 0.995 with the reference signal and the dynamic range to be 120dB@63Hz.
基金supported by the National Key R&D Program of China(Nos.2021YFA0805700 and 2021YFA1102000)the National Natural Science Foundation of China(No.U2102204)the Natural Science Foundation of Yunnan Province,China(Nos.202001BC070001 and 202102AA100053)。
文摘Efforts have been made to establish various human pluripotent stem cell lines.However,such methods have not yet been duplicated in non-human primate cells.Here,we introduce a multiplexed single-cell sequencing technique to profile the molecular features of monkey pluripotent stem cells in published culture conditions.The results demonstrate suboptimized maintenance of pluripotency and show that the selected signaling pathways for resetting human stem cells can also be interpreted for establishing monkey cell lines.Overall,this work legitimates the translation of novel human cell line culture conditions to monkey cells and provides guidance for exploring chemical cocktails for monkey stem cell line derivation.
基金support from the National Natural Sci-ence Foundation of China(grant nos.T2225010,32171399,and 32171456)Guangdong Basic and Applied Basic Research Foundation(grant no.2023A1515011267)+1 种基金Science and Technalogy Program of Guangzhou,China(grant nos.2024B03J0121 and 2024B03J1284)the Independent Fund of the State Key Laboratory of Optoelectronic Ma-terials and Technologies(Sun YatSen University)under grant no.
文摘Monitoring multiplexed biochemical markers is beneficial for the comprehensive evaluation of diabetes-associated complications.Techniques for multiplexed analyses in interstitial fluids have often been restricted by the difficulties of electrode materials in accurately detecting chemicals in complex subcutaneous spaces.In particular,the signal stability of enzyme-based sensing electrodes often inevitably decreases due to enzyme degradation or interference in vivo.In this study,we developed a self-calibrating multiplexed microneedle(MN)electrode array(SC-MMNEA)capable of continuous,real-time monitoring of multiple types of bioanalytes(glucose,cholesterol,uric acid,lactate,reactive oxygen species[ROSs],Na+,K+,Ca2+,and pH)in the subcutaneous space.Each type of analyte was detected by a discrete MN electrode assembled in an integrated array with single-MN resolution.Moreover,this device utilized an MN-delivery-mediated self-calibration technique to address the inherent problem of decreased accuracy of implantable electrodes caused by long-term tissue variation and enzyme degradation,and this technique might increase the reliability of the MN sensors.Our results indicated that SC-MMNEA could provide real-time monitoring of multiplexed analyte concentrations in a rat model with good accuracy,especially after self-calibration.SC-MMNEA has the advantages of in situ and minimally invasive monitoring of physiological states and the potential to promote wearable devices for long-term monitoring of chemical species in vivo.
基金supported by the National 863 Program under Grant No. 2006AA01Z217the National Natural Science Foundation of China under Grant No. 60736039College Science Research Foundation of Tianjin and the Key Laboratory of Optoelectronic Information Technical Science, Ministry of Education of China under Grant No. 2006BA28
文摘A laser sensing system based on beat frequency demodulation is proposed. The sensor uses a single-longitudinal-mode distributed Bragg reflector （DBR） fiber laser as a sensing element. This laser sensor has great multiplexing capability due to its wide free spectral range. Wavelength-division-multiplex （WDM） and frequency-division-multiplex （FDM） techniques are studied. The sensing system has high sensitivity and multiplexing channels.
基金Project supported by the National Natural Science Foundation of China (Grant No.61003082)
文摘Nanocrossbar is a potential memory architecture to integrate memristor to achieve large scale and high density mem- ory. However, based on the currently widely-adopted parallel reading scheme, scalability of the nanocrossbar memory is limited, since the overhead of the reading circuits is in proportion with the size of the nanocrossbar component. In this paper, a multiplexed reading scheme is adopted as the foundation of the discussion. Through HSPICE simulation, we reanalyze scalability of the nanocrossbar memristor memory by investigating the impact of various circuit parameters on the output voltage swing as the memory scales to larger size. We find that multiplexed reading maintains sufficient noise margin in large size nanocrossbar memristor memory. In order to improve the scalability of the memory, memristors with nonlinear I-V characteristics and high LRS （low resistive state） resistance should be adopted.
基金National Science Foundation,Grant number CMS-9900338
文摘Development and testing of a serially multiplexed fiber optic sensor system is described.The sensor differs from conventional fiber optic acoustic systems,as it is capable of sensing AE emissions at several points along the length of a single fiber.Multiplexing provides for single channel detection of cracks and their locations in large structural systems. An algorithm was developed for signal recognition and tagging of the AE waveforms for detection of' crack locations,Labora- tory experiments on plain concrete beams and post-tensioned FRP tendons were pcrlormed to evaluate the crack detection capability of the sensor system.The acoustic emission sensor was able to detect initiation,growth and location of the cracks in concrete as well as in the FRP tendons.The AE system is potentially suitable lot applications involving health monitoring of structures following an earthquake.
文摘During the last decades the whispering gallery mode based sensors have become a prominent solution for label-free sensing of various physical and chemical parameters.At the same time,the widespread utilization of the approach is hindered by the restricted applicability of the known configurations for ambient variations quantification outside the laboratory conditions and their low affordability,where necessity on the spectrally-resolved data collection is among the main limiting factors.In this paper we demonstrate the first realization of an affordable whispering gallery mode sensor powered by deep learning and multi-resonator imaging at a fixed frequency.It has been shown that the approach enables refractive index unit(RIU)prediction with an absolute error at 3×10^(-6) level for dynamic range of the RIU variations from 0 to 2×10^(-3) with temporal resolution of several milliseconds and instrument-driven detection limit of 3×10−5.High sensing accuracy together with instrumental affordability and production simplicity places the reported detector among the most cost-effective realizations of the whispering gallery mode approach.The proposed solution is expected to have a great impact on the shift of the whole sensing paradigm away from the model-based and to the flexible self-learning solutions.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61271238 and 61475075)the Open Research Fund of Key Lab of Broadband Wireless Communication and Sensor Network Technology,Ministry of Education,China(Grant No.NYKL2015011)+1 种基金the Postgraduate Innovation Research Plan of Jiangsu Province,China(Grant No.CXZZ13_0489)the University Natural Science Foundation of Jiangsu Province,China(Grant No.16KJB510037)
文摘Atmospheric turbulence（AT） induced crosstalk can significantly impair the performance of a free-space optical（FSO）communication link using orbital angular momentum（OAM） multiplexing.In this paper,we propose a multiple-user detection（MUD） turbulence mitigation scheme in an OAM-multiplexed FSO communication link.First,we present a MUD equivalent communication model for an OAM-multiplexed FSO communication link under AT.In the equivalent model,each input bit stream represents one user＇s information.The deformed OAM spatial modes caused by AT,instead of the pure OAM spatial modes,are used as information carriers,and the overlapping between the deformed OAM spatial modes are computed as the correlation coefficients between the users.Then,we present a turbulence mitigation scheme based on MUD idea to enhance AT tolerance of the OAM-multiplexed FSO communication link.In the proposed scheme,the crosstalk caused by AT is used as a useful component to deduce users＇ information.The numerical results show that the performance of the OAM-multiplexed communication link has greatly improved by the proposed scheme.When the turbulence strength C_n^2 is 1 × 10^（-15） m^（-2/3）,the transmission distance is 1000 m and the channel signal-to-noise ratio（SNR）is 26 dB,the bit-error-rate（BER） performance of four spatial multiplexed OAM modes l_m = ＋ 1,＋2,＋3,＋4 are all close to 10-5,and there is a 2-3 fold increase in the BER performance in comparison with those results without the proposed scheme.In addition,the proposed scheme is more effective for an OAM-multiplexed FSO communication link with a larger OAM mode topological charge interval.The proposed scheme is a promising direction for compensating the interference caused by AT in the OAM-multiplexed FSO communication link.
基金supported by the National Basic Research Program of China(Grant No.2007CB3070001)the Fundamental Research Funds for the Central Universities,China(Grant No.HIT.NSRIF.2010009)+1 种基金the Program of Excellent Team in Harbin Institute of Technology,Chinathe Research Startup Foundation of Civil Aviation University of China(Grant No.2010QN03X)
文摘In this paper, we experimentally investigate the dark diffusional enhancement of the optimized multiplexed grating in the phenanthrenequinone doped poly （methyl methacrylate） （PQ-PMMA） photopolymer. The possibility of improving the holographic characteristics of the material through the dark enhancement is demonstrated. The optimal preillumination exposure and the optimal time interval between exposures are extracted to obtain the optimized diffraction efficiency, and their values are 3.4×103 mJ/cm2 and 2 min, respectively. The dark enhancement of the multiplexed grating is presented as an effective method to improve the response region and the dynamic range and to prevent saturation of the material. The dependence of the phenanthrenequinone concentration on the increment of the refractive index modulation is quantitatively studied, which provides a significant basis for improving the homogeneity in the multiplexed gratings using a quantitative strategy. Finally, a simple experimental procedure using the dark enhancement is introduced to improve the homogeneity of the diffraction efficiency and to avoid the complex schedule exposure.
