Super-resolution structured illumination microscopy(SR-SIM)relies heavily on post-processing reconstruction to obtain high-quality SR images from raw data.Although many SIM reconstruction algorithms have been develope...Super-resolution structured illumination microscopy(SR-SIM)relies heavily on post-processing reconstruction to obtain high-quality SR images from raw data.Although many SIM reconstruction algorithms have been developed to recover fine cellular structures with high fidelity even from the noisy data,whether the pixel intensities of reconstructed SR images are still proportional to the original fluorescence intensity has been less explored.The linearity between the intensity before and after reconstruction is de fined as the intensity fidelity.Here,we proposed a method to evaluate the reconstructed SR image intensity fidelity at different spatial frequencies.With the proposed metric,we systematically investigated the impact of the key factors on the intensity fidelity in the standard Wiener-SIM reconstructions with simulated data,then evaluated the intensity fidelity of the SR images reconstructed by representative open-source packages.Our work provides a reference for SR-SIM image intensity fidelity improvement.展开更多
Maintaining the s-polarization state of laser beams is important to achieve high modulation depth in a laser-interference-based super-resolution structured illumination microscope(SR-SIM).However,the imperfect optical...Maintaining the s-polarization state of laser beams is important to achieve high modulation depth in a laser-interference-based super-resolution structured illumination microscope(SR-SIM).However,the imperfect optical components can depolarize the laser beams hence degenerating the modulation depth.Here,we first presented a direct measurement method designed to estimate the modulation depth more precisely by shifting illumination patterns with equal phase steps.This measurement method greatly reduces the dependence of modulation depths on the samples,and then developed a polarization optimization method to achieve high modulation depth at all orientations by actively and quantitatively compensating for the additional phase difference using a combination of waveplate and a liquid crystal variable retarder(LCVR).Experimental results demonstrate that our method can achieve illumination patterns with modulation depth higher than 0.94 at three orientations with only one LCVR voltage,which enables isotropic resolution improvement.展开更多
Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scat...Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scattering cause shading of the light-sheet illumination,preventing the even 3D image of thick samples.Herein,we report a continuous-rotational light-sheet microscope(CR-LSM)that enables simultaneous 3D bright-field and fluorescence imaging.With a high-accuracy rotational stage,CR-LSM records the outline projections and the fluorescent images of the sample at multiple rotation angles.Then,3D morphology and fluorescent structure were reconstructed with a developed algorithm.Using CR-LSM,zebrafish’s whole-fish contour and blood vessel structures were obtained simultaneously.展开更多
The process of wound healing is routinely evaluated by histological evaluation in the clinic,which may cause scarring and secondary injury.Reflectance confocal microscopy(RCM)represents a noninvasive,real-time imaging...The process of wound healing is routinely evaluated by histological evaluation in the clinic,which may cause scarring and secondary injury.Reflectance confocal microscopy(RCM)represents a noninvasive,real-time imaging technique that allows in vivo evaluation of the skin.Traditional RCM was wide-probe-based,which limited its application on uneven and covered skin.In this study,we report the development of a portable reflectance confocal microscope(PRCM)in which all components were assembled in a handheld shell.Although the size and weight of the PRCM were reduced based on the use of a microelectromechanical system,the resolution was kept at 0.91μm,and the field of view of the system was 343μm×532μm.When used in vivo,the PRCM was able to visualize cellular and nuclear morphology for both mouse and human skin.PRCM evaluations were then performed on wounds after topically applied mesenchymal stem cells(MSCs)or saline treatment.The PRCM allowed visualization of the formation of collagen bundles,re-epithelization from the wound edge to the wound bed,and hair follicle regeneration,which were consistent with histological evaluations.Therefore,we offer new insights into monitoring the effects of topically applied MSCs on the process of wound healing by using PRCM.This study illustrates that the newly developed PRCM represents a promising device for real-time,noninvasive monitoring of the dynamic process of wound healing,which demonstrates its potential to diagnose,monitor,or predict disease in clinical wound therapy.展开更多
Objective and Impact Statement:We describe an electroenzymatic mediator(EM)sensor based on an electroenzymatic assembly peak separation strategy,which can efficiently realize the simultaneous detection of 3 typical ca...Objective and Impact Statement:We describe an electroenzymatic mediator(EM)sensor based on an electroenzymatic assembly peak separation strategy,which can efficiently realize the simultaneous detection of 3 typical cardiovascular disease(CVD)metabolites in 5μl of plasma under one test.This work has substantial implications toward improving the efficiency of chronic CVD assessment.Introduction:Monitoring CVD of metabolites is strongly associated with disease risk.Independent and time-consuming detection in hospitals is unfavorable for chronic CVD management.Methods:The EM was flexibly designed by the cross-linking of electron mediators and enzymes,and 3 EM layers with different characteristics were assembled on one electrode.Electrons were transferred under tunable potential;3 metabolites were quantitatively detected by 3 peak currents that correlated with metabolite concentrations.Results:In this study,the EM sensor showed high sensitivity for the simultaneous detection of 3 metabolites with a lower limit of 0.01 mM.The linear correlation between the sensor and clinical was greater than 0.980 for 242 patients,and the consistency of risk assessment was 94.6%.Conclusion:Metabolites could be expanded by the EM,and the sensor could be a promising candidate as a home healthcare tool for CVD risk assessment.展开更多
In recent years,significant progress has been made in the development of organoids,which offer promising opportunities for developmental and translational research.With advances in cell biology and bioengineering tech...In recent years,significant progress has been made in the development of organoids,which offer promising opportunities for developmental and translational research.With advances in cell biology and bioengineering techniques,skin models are evolving from conventional multilayered structures to appendage-bearing spheroids or 3D biomimetic models.This comprehensive review aims to provide an in-depth understanding of organoid models of the skin,covering topics such as skin development,construction strategies and key elements,types of organoid models,biomedical applications,and challenges.Embryonic skin development is briefly introduced to provide a foundational understanding of construction principles.Current engineering strategies are outlined,highlighting key elements such as cell sources,bioengineering techniques,3D scaffolds,and crucial signaling pathways.Furthermore,recent advances in generating organoids with structural and functional parallels to native skin are meticulously summarized.These developments facilitate the utilization of organoids in diverse applications,such as modeling skin disorders,developing regenerative solutions,and understanding skin development.Finally,the challenges and prospects in the field are discussed.The integration of state-of-the-art bioengineering techniques with a deep understanding of skin biology is promoting the production and biomedical application of these organoid models.展开更多
Photoacoustic imaging(PAI)employs short laser pulses to excite absorbing materials,producing ultrasonic waves spanning a broad spectrum of frequencies.These ultrasonic waves are captured surrounding the sample and uti...Photoacoustic imaging(PAI)employs short laser pulses to excite absorbing materials,producing ultrasonic waves spanning a broad spectrum of frequencies.These ultrasonic waves are captured surrounding the sample and utilized to reconstruct the initial pressure distribution tomographically.Despite the wide spectral range of the laser-generated photoacoustic signal,an individual transducer can only capture a limited segment of the signal due to its constrained bandwidth.Herein,we have developed a multi-bandwidth ring array photoacoustic computed tomography(PACT)system,incorporating a probe with two semi-ring arrays:one for high frequency and the other for low frequency.Utilizing the two semi-ring array PAIs,we have devised a specialized deep learning model,comprising two serially connected U-net architectures,to autonomously generate multi-bandwidth full-view PAIs.Preliminary results from simulations and in vivo experiments illustrate the system's robust multi-bandwidth imaging capabilities,achieving an excellent PSNR of 34.78 dB and a structural similarity index measure(SSIM)of 0.94 in the high-frequency reconstruction of complex mouse abdominal structures.This innovative PACT system is notable for its capability to seamlessly acquire multi-bandwidth full-view PAIs,thereby advancing the application of PAI technology in the biomedical domain.展开更多
The prediction of fundus fluorescein angiography(FFA)images from fundus structural images is a cutting-edge research topic in ophthalmological image processing.Prediction comprises estimating FFA from fundus camera im...The prediction of fundus fluorescein angiography(FFA)images from fundus structural images is a cutting-edge research topic in ophthalmological image processing.Prediction comprises estimating FFA from fundus camera imaging,single-phase FFA from scanning laser ophthalmoscopy(SLO),and three-phase FFA also from SLO.Although many deep learning models are available,a single model can only perform one or two of these prediction tasks.To accomplish three prediction tasks using a unified method,we propose a unified deep learning model for predicting FFA images from fundus structure images using a supervised generative adversarial network.The three prediction tasks are processed as follows:data preparation,network training under FFA supervision,and FFA image prediction from fundus structure images on a test set.By comparing the FFA images predicted by our model,pix2pix,and CycleGAN,we demonstrate the remarkable progress achieved by our proposal.The high performance of our model is validated in terms of the peak signal-to-noise ratio,structural similarity index,and mean squared error.展开更多
There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)...There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma surgery.Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments.After surgery,a subjective feedback survey about the user experience was taken.The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery.The custom-made instruments also solved the shadowing problem in OCT imaging.Surgeons preferred to use the system in their future practice.展开更多
As the key component of wireless data transmission and powering,stretchable antennas play an indispensable role in flexible/stretchable electronics.However,they often suffer from frequency detuning upon mechanical def...As the key component of wireless data transmission and powering,stretchable antennas play an indispensable role in flexible/stretchable electronics.However,they often suffer from frequency detuning upon mechanical deformations;thus,their applications are limited to wireless sensing with wireless transmission capabilities remaining elusive.Here,a hierarchically structured stretchable microstrip antenna with meshed patterns arranged in an arched shape showcases tunable resonance frequency upon deformations with improved overall stretchability.The almost unchanged resonance frequency during deformations enables robust on-body wireless communication and RF energy harvesting,whereas the rapid changing resonance frequency with deformations allows for wireless sensing.The proposed stretchable microstrip antenna was demonstrated to communicate wirelessly with a transmitter(input power of−3 dBm)efficiently(i.e.,the receiving power higher than−100 dBm over a distance of 100 m)on human bodies even upon 25%stretching.The flexibility in structural engineering combined with the coupled mechanical-electromagnetic simulations,provides a versatile engineering toolkit to design stretchable microstrip antennas and other potential wireless devices for stretchable electronics.展开更多
Atomic magnetometers operated in the spin-exchange relaxation-free(SERF)regime are the promising sensor to replace superconducting quantum interference devices(SQUIDs)in the biomagnetism field.The SERF magnetometer wi...Atomic magnetometers operated in the spin-exchange relaxation-free(SERF)regime are the promising sensor to replace superconducting quantum interference devices(SQUIDs)in the biomagnetism field.The SERF magnetometer with compact size and good performance is crucial to the new generation of wearable magnetoencephalography(MEG)system.In this paper,we developed a compact and closed-loop SERF magnetometer with the dimensions of 15.0×22.0×30.0 mm^(3)based on a single-beam configuration.The bandwidth of the magnetometer was extended to 675 Hz while the sensitivity was maintained at 22 f T/Hz^(1/2).A nearly 3-fold enhancement of the bandwidth was obtained in comparison with the open-loop control.The implementation of the closed-loop control also greatly improved the dynamic range,enabling the magnetometer to be robust against the disturbance of the ambient field.Moreover,the magnetometer was successfully applied for the detection of humanα-rhythm and auditory evoked fields(AEFs),which demonstrated the potential to be extended to multi-channel MEG measurements for future neuroscience studies.展开更多
With advantages of small volume,high field strength,and compact stray field,the Halbach array magnet is of great potential in desktop NMR applications.However,field inhomogeneity poses a main obstacle to its applicati...With advantages of small volume,high field strength,and compact stray field,the Halbach array magnet is of great potential in desktop NMR applications.However,field inhomogeneity poses a main obstacle to its applications.Active shimming is necessary for improving the field homogeneity.An active shim coil design method for cylindrical Halbach magnet based on inverse boundary element method(iBEM)is introduced in this work.Shim coils targeting 1st~3rd and Z4/Z5/Z6 spherical harmonic(SH)terms were designed with constraints of field accuracy,resistance,inductance,and current density.Wire loops and symmetric property influence were discussed to further improve the performance of high-order shim coils.Finally,with the prototype of the shim coils constructed,field pattern and SH transformation proved that the coils designed could fit the target SH distribution,though contamination from low-order components existed in highorder terms.A practical shimming experiment on the Halbach magnet has improved the homogeneity from 40.3 ppm to 3.8 ppm in radius 2.5 mm,height 5 mm cylindrical sample space,verifying the coils'compensation ability.This work provides a flexible inverse coil design method for cylindrical Halbach magnet and discusses the high-order shim coil design and implementation,which is potential in nuclear magnetic resonance applications based on Halbach magnet arrays.展开更多
Objective The detection of RNA single nucleotide polymorphism(SNP)is of great importance due to their association with protein expression related to various diseases and drug responses.At present,splintR ligase-assist...Objective The detection of RNA single nucleotide polymorphism(SNP)is of great importance due to their association with protein expression related to various diseases and drug responses.At present,splintR ligase-assisted methods are important approaches for RNA direct detection,but its specificity will be limited when the fidelity of ligases is not ideal.The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection.Methods In this study,a dualcompetitive-padlock-probe(DCPLP)assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation.To verify the method,we employed dual competitive padlock probe-mediated rolling circle amplification(DCPLP-RCA)to genotype the CYP2C9 gene.Results The specificity was well improved through the competition and strand displacement of dual padlock probe,with an 83.26%reduction in nonspecific signal.By detecting synthetic RNA samples,the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L.Furthermore,clinical samples were applied to the method to evaluate its performance,and the genotyping results were consistent with those obtained using the qPCR method.Conclusion This study has successfully established a highly specific direct RNA SNP detection method,and provided a novel avenue for accurate identification of various types of RNAs.展开更多
Objective Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate ...Objective Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus(AAV)vector encodingβ-catenin to treat AMD in a mouse model.Methods Mice were intravitreally injected with AAV2/8-Y733F-VMD2-β-catenin for 2 or 4 weeks,andβ-catenin expression was measured using immunofluorescence staining,real-time quantitative reverse transcription polymerase chain reaction(PCR),and Western blotting.The function ofβ-catenin was determined using retinal flat mounts and laser-induced damage models.Finally,the safety of AAV2/8-Y733F-VMD2-β-catenin was evaluated by multiple intravitreal injections.Results AAV2/8-Y733F-VMD2-β-catenin induced the expression ofβ-catenin in RPE cells.It activated the proliferation of RPE cells and increased cyclin D1 expression.It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells.Furthermore,it could induce apoptosis of RPE cells by increasing the expression of Trp53,Bax and caspase3 while decreasing the expression of Bcl-2.Conclusion AAV2/8-Y733F-VMD2-β-catenin increasedβ-catenin expression in RPE cells,activated RPE cell proliferation,and helped mice heal from laser-induced eye injury.Furthermore,it could induce the apoptosis of RPE cells.Therefore,it may be a safe approach for AMD treatment.展开更多
Structured illumination microscopy(SIM)is a popular and powerful super-resolution(SR)technique in biomedical research.However,the conventional reconstruction algorithm for SIM heavily relies on the accurate prior know...Structured illumination microscopy(SIM)is a popular and powerful super-resolution(SR)technique in biomedical research.However,the conventional reconstruction algorithm for SIM heavily relies on the accurate prior knowledge of illumination patterns and signal-to-noise ratio(SNR)of raw images.To obtain high-quality SR images,several raw images need to be captured under high fluorescence level,which further restricts SIM’s temporal resolution and its applications.Deep learning(DL)is a data-driven technology that has been used to expand the limits of optical microscopy.In this study,we propose a deep neural network based on multi-level wavelet and attention mechanism(MWAM)for SIM.Our results show that the MWAM network can extract high-frequency information contained in SIM raw images and accurately integrate it into the output image,resulting in superior SR images compared to those generated using wide-field images as input data.We also demonstrate that the number of SIM raw images can be reduced to three,with one image in each illumination orientation,to achieve the optimal tradeoff between temporal and spatial resolution.Furthermore,our MWAM network exhibits superior reconstruction ability on low-SNR images compared to conventional SIM algorithms.We have also analyzed the adaptability of this network on other biological samples and successfully applied the pretrained model to other SIM systems.展开更多
Recently,a study on a 0.05 T,low-cost,low-power,and computing-driven shielding-free ultra-low-field(ULF)magnetic resonance imaging(MRI)scannerwas published.This work enhances the image quality of MRI and reduces the s...Recently,a study on a 0.05 T,low-cost,low-power,and computing-driven shielding-free ultra-low-field(ULF)magnetic resonance imaging(MRI)scannerwas published.This work enhances the image quality of MRI and reduces the scanning time based on deep learning methods,which is of great significance to enhancing the popularization and availability of MRI[1](https://www.science.org/doi/abs/10.1126/science.adm7168).展开更多
Sputum smear tests are critical for the diagnosis of respiratory diseases. Automatic segmentation of bacteria from spu-tum smear images is important for improving diagnostic efficiency. However, this remains a challen...Sputum smear tests are critical for the diagnosis of respiratory diseases. Automatic segmentation of bacteria from spu-tum smear images is important for improving diagnostic efficiency. However, this remains a challenging task owing to the high interclass similarity among different categories of bacteria and the low contrast of the bacterial edges. To explore more levels of global pattern features to promote the distinguishing ability of bacterial categories and main-tain sufficient local fine-grained features to ensure accurate localization of ambiguous bacteria simultaneously, we propose a novel dual-branch deformable cross-attention fusion network (DB-DCAFN) for accurate bacterial segmen-tation. Specifically, we first designed a dual-branch encoder consisting of multiple convolution and transformer blocks in parallel to simultaneously extract multilevel local and global features. We then designed a sparse and deformable cross-attention module to capture the semantic dependencies between local and global features, which can bridge the semantic gap and fuse features effectively. Furthermore, we designed a feature assignment fusion module to enhance meaningful features using an adaptive feature weighting strategy to obtain more accurate segmentation. We conducted extensive experiments to evaluate the effectiveness of DB-DCAFN on a clinical dataset comprising three bacterial categories: Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The experi-mental results demonstrate that the proposed DB-DCAFN outperforms other state-of-the-art methods and is effective at segmenting bacteria from sputum smear images.展开更多
1.Introduction Light-sheet fluorescence microscopy(LSFM),since it was first coined the term selective-plane-illumination microscopy(SPIM)by Huisken et al.[1],has been developed for nearly two decades,needless to menti...1.Introduction Light-sheet fluorescence microscopy(LSFM),since it was first coined the term selective-plane-illumination microscopy(SPIM)by Huisken et al.[1],has been developed for nearly two decades,needless to mention a landmark development of digitally scanned light-sheet microscopy(DSLM)innovated by Keller et al.[2].展开更多
Low-dose computed tomography(LDCT)has gained increasing attention owing to its crucial role in reducing radiation exposure in patients.However,LDCT-reconstructed images often suffer from significant noise and artifact...Low-dose computed tomography(LDCT)has gained increasing attention owing to its crucial role in reducing radiation exposure in patients.However,LDCT-reconstructed images often suffer from significant noise and artifacts,negatively impacting the radiologists’ability to accurately diagnose.To address this issue,many studies have focused on denoising LDCT images using deep learning(DL)methods.However,these DL-based denoising methods have been hindered by the highly variable feature distribution of LDCT data from different imaging sources,which adversely affects the performance of current denoising models.In this study,we propose a parallel processing model,the multi-encoder deep feature transformation network(MDFTN),which is designed to enhance the performance of LDCT imaging for multisource data.Unlike traditional network structures,which rely on continual learning to process multitask data,the approach can simultaneously handle LDCT images within a unified framework from various imaging sources.The proposed MDFTN consists of multiple encoders and decoders along with a deep feature transformation module(DFTM).During forward propagation in network training,each encoder extracts diverse features from its respective data source in parallel and the DFTM compresses these features into a shared feature space.Subsequently,each decoder performs an inverse operation for multisource loss estimation.Through collaborative training,the proposed MDFTN leverages the complementary advantages of multisource data distribution to enhance its adaptability and generalization.Numerous experiments were conducted on two public datasets and one local dataset,which demonstrated that the proposed network model can simultaneously process multisource data while effectively suppressing noise and preserving fine structures.The source code is available at https://github.com/123456789ey/MDFTN.展开更多
The widely used Shack-Hartmann wavefront sensor(SHWFS)is a wavefront measurement system.Its measurement accuracy is limited by the reference wavefront used for calibration and also by various residual errors of the se...The widely used Shack-Hartmann wavefront sensor(SHWFS)is a wavefront measurement system.Its measurement accuracy is limited by the reference wavefront used for calibration and also by various residual errors of the sensor itself.In this study,based on the principle of spherical wavefront calibration,a pinhole with a diameter of 1μm was used to generate spherical wavefronts with extremely small wavefront errors,with residual aberrations of 1.0×10^(−4)λRMS,providing a high-accuracy reference wavefront.In the first step of SHWFS calibration,we demonstrated a modified method to solve for three important parameters(f,the focal length of the microlens array(MLA),p,the sub-aperture size of the MLA,and s,the pixel size of the photodetector)to scale the measured SHWFS results.With only three iterations in the calculation,these parameters can be determined as exact values,with convergence to an acceptable accuracy.For a simple SHWFS with an MLA of 128×128 sub-apertures in a square configuration and a focal length of 2.8 mm,a measurement accuracy of 5.0×10^(−3)λRMS was achieved across the full pupil diameter of 13.8 mm with the proposed spherical wavefront calibration.The accuracy was dependent on the residual errors induced in manufacturing and assembly of the SHWFS.After removing these residual errors in the measured wavefront results,the accuracy of the SHWFS increased to 1.0×10^(−3)λRMS,with measured wavefronts in the range ofλ/4.Mid-term stability of wavefront measurements was confirmed,with residual deviations of 8.04×10^(−5)λPV and 7.94×10^(−5)λRMS.This study demonstrates that the modified calibration method for a high-accuracy spherical wavefront generated from a micrometer-scale pinhole can effectively improve the accuracy of an SHWFS.Further accuracy improvement was verified with correction of residual errors,making the method suitable for challenging wavefront measurements such as in lithography lenses,astronomical telescope systems,and adaptive optics.展开更多
基金supported by the National Natural Science Foundation of China[Grant Nos.62205367 and 62141506]Suzhou Basic Research Pilot Project[Grant Nos.SSD2023006 and SJC2021013]Jiangsu Provincial Key Research and Development Program[Grant No.BE2020664].
文摘Super-resolution structured illumination microscopy(SR-SIM)relies heavily on post-processing reconstruction to obtain high-quality SR images from raw data.Although many SIM reconstruction algorithms have been developed to recover fine cellular structures with high fidelity even from the noisy data,whether the pixel intensities of reconstructed SR images are still proportional to the original fluorescence intensity has been less explored.The linearity between the intensity before and after reconstruction is de fined as the intensity fidelity.Here,we proposed a method to evaluate the reconstructed SR image intensity fidelity at different spatial frequencies.With the proposed metric,we systematically investigated the impact of the key factors on the intensity fidelity in the standard Wiener-SIM reconstructions with simulated data,then evaluated the intensity fidelity of the SR images reconstructed by representative open-source packages.Our work provides a reference for SR-SIM image intensity fidelity improvement.
基金supported by the National Natural Science Foundation of China[Grant Nos.62205367 and 62141506]the Suzhou Basic Research Pilot Project[Grant Nos.SSD2023006 and SJC2021013]the National Key Research and Development Program of China[Grant No.2023YFF1205700].
文摘Maintaining the s-polarization state of laser beams is important to achieve high modulation depth in a laser-interference-based super-resolution structured illumination microscope(SR-SIM).However,the imperfect optical components can depolarize the laser beams hence degenerating the modulation depth.Here,we first presented a direct measurement method designed to estimate the modulation depth more precisely by shifting illumination patterns with equal phase steps.This measurement method greatly reduces the dependence of modulation depths on the samples,and then developed a polarization optimization method to achieve high modulation depth at all orientations by actively and quantitatively compensating for the additional phase difference using a combination of waveplate and a liquid crystal variable retarder(LCVR).Experimental results demonstrate that our method can achieve illumination patterns with modulation depth higher than 0.94 at three orientations with only one LCVR voltage,which enables isotropic resolution improvement.
基金the National Natural Science Foundation of China(62205368)the Key Research and Development Program of Jiangsu Province(BE2020664).
文摘Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scattering cause shading of the light-sheet illumination,preventing the even 3D image of thick samples.Herein,we report a continuous-rotational light-sheet microscope(CR-LSM)that enables simultaneous 3D bright-field and fluorescence imaging.With a high-accuracy rotational stage,CR-LSM records the outline projections and the fluorescent images of the sample at multiple rotation angles.Then,3D morphology and fluorescent structure were reconstructed with a developed algorithm.Using CR-LSM,zebrafish’s whole-fish contour and blood vessel structures were obtained simultaneously.
基金the National Key Research andDevelopment Program of China(No.2021YFA1101100)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16020807)+3 种基金the Major Innovative Research Team of Suzhou,China(No.ZXT2019007)Suzhou Institute of Biomedical Engineering and Technology(SIBET)Jilin City Science and Technology Cooperation Project(No.E0550104)Science and Technology Innovation Talents in Universities of Henan Province and Doctor of Entrepreneurship and Innovation Program of Jiangsu Province in the year of 2020.
文摘The process of wound healing is routinely evaluated by histological evaluation in the clinic,which may cause scarring and secondary injury.Reflectance confocal microscopy(RCM)represents a noninvasive,real-time imaging technique that allows in vivo evaluation of the skin.Traditional RCM was wide-probe-based,which limited its application on uneven and covered skin.In this study,we report the development of a portable reflectance confocal microscope(PRCM)in which all components were assembled in a handheld shell.Although the size and weight of the PRCM were reduced based on the use of a microelectromechanical system,the resolution was kept at 0.91μm,and the field of view of the system was 343μm×532μm.When used in vivo,the PRCM was able to visualize cellular and nuclear morphology for both mouse and human skin.PRCM evaluations were then performed on wounds after topically applied mesenchymal stem cells(MSCs)or saline treatment.The PRCM allowed visualization of the formation of collagen bundles,re-epithelization from the wound edge to the wound bed,and hair follicle regeneration,which were consistent with histological evaluations.Therefore,we offer new insights into monitoring the effects of topically applied MSCs on the process of wound healing by using PRCM.This study illustrates that the newly developed PRCM represents a promising device for real-time,noninvasive monitoring of the dynamic process of wound healing,which demonstrates its potential to diagnose,monitor,or predict disease in clinical wound therapy.
基金This work was supported by the National Key R&D Program of China(2021YFB3201202)the National Natural Science Foundation of China(nos.22005331,52275581,and 82372142)+3 种基金the Key Research and Development Program of Jiang su Province(nos.BE2022739,BE2020768,and SBE2022780090)the Youth Innovation Promotion Association of CAS(nos.2019322 and Y2022088)the Instrument Developing Project of the Chinese Academy of Sciences(nos.YJKYYQ20200046 and ZDKYYQ20210004)the Science and Technology Development Program of Suzhou(no.SJC2021019).
文摘Objective and Impact Statement:We describe an electroenzymatic mediator(EM)sensor based on an electroenzymatic assembly peak separation strategy,which can efficiently realize the simultaneous detection of 3 typical cardiovascular disease(CVD)metabolites in 5μl of plasma under one test.This work has substantial implications toward improving the efficiency of chronic CVD assessment.Introduction:Monitoring CVD of metabolites is strongly associated with disease risk.Independent and time-consuming detection in hospitals is unfavorable for chronic CVD management.Methods:The EM was flexibly designed by the cross-linking of electron mediators and enzymes,and 3 EM layers with different characteristics were assembled on one electrode.Electrons were transferred under tunable potential;3 metabolites were quantitatively detected by 3 peak currents that correlated with metabolite concentrations.Results:In this study,the EM sensor showed high sensitivity for the simultaneous detection of 3 metabolites with a lower limit of 0.01 mM.The linear correlation between the sensor and clinical was greater than 0.980 for 242 patients,and the consistency of risk assessment was 94.6%.Conclusion:Metabolites could be expanded by the EM,and the sensor could be a promising candidate as a home healthcare tool for CVD risk assessment.
基金funded by the National Key Research and Development Program of China(grant/award number:2021YFA1101100,2022YFA1104800)National Natural Science Foundation of China(grant/award number:82271522)Basic Research Priorities Program of Jiangsu Province(grant/award number:BK20243003).
文摘In recent years,significant progress has been made in the development of organoids,which offer promising opportunities for developmental and translational research.With advances in cell biology and bioengineering techniques,skin models are evolving from conventional multilayered structures to appendage-bearing spheroids or 3D biomimetic models.This comprehensive review aims to provide an in-depth understanding of organoid models of the skin,covering topics such as skin development,construction strategies and key elements,types of organoid models,biomedical applications,and challenges.Embryonic skin development is briefly introduced to provide a foundational understanding of construction principles.Current engineering strategies are outlined,highlighting key elements such as cell sources,bioengineering techniques,3D scaffolds,and crucial signaling pathways.Furthermore,recent advances in generating organoids with structural and functional parallels to native skin are meticulously summarized.These developments facilitate the utilization of organoids in diverse applications,such as modeling skin disorders,developing regenerative solutions,and understanding skin development.Finally,the challenges and prospects in the field are discussed.The integration of state-of-the-art bioengineering techniques with a deep understanding of skin biology is promoting the production and biomedical application of these organoid models.
基金supported by the National Key R&D Program of China[Grant No.2023YFF0713600]the National Natural Science Foundation of China[Grant No.62275062]+2 种基金the Project of Shandong Innovation and Startup Community of High-end Medical Apparatus and Instruments[Grant No.2021-SGTTXM-005]the Shandong Province Technology Innovation Guidance Plan(Central Leading Local Science and Technology Development Fund)[Grant No.YDZX2023115]the Taishan Scholar Special Funding Project of Shandong Province,and the Shandong Laboratory of Advanced Biomaterials and Medical Devices in Weihai[Grant No.ZL202402].
文摘Photoacoustic imaging(PAI)employs short laser pulses to excite absorbing materials,producing ultrasonic waves spanning a broad spectrum of frequencies.These ultrasonic waves are captured surrounding the sample and utilized to reconstruct the initial pressure distribution tomographically.Despite the wide spectral range of the laser-generated photoacoustic signal,an individual transducer can only capture a limited segment of the signal due to its constrained bandwidth.Herein,we have developed a multi-bandwidth ring array photoacoustic computed tomography(PACT)system,incorporating a probe with two semi-ring arrays:one for high frequency and the other for low frequency.Utilizing the two semi-ring array PAIs,we have devised a specialized deep learning model,comprising two serially connected U-net architectures,to autonomously generate multi-bandwidth full-view PAIs.Preliminary results from simulations and in vivo experiments illustrate the system's robust multi-bandwidth imaging capabilities,achieving an excellent PSNR of 34.78 dB and a structural similarity index measure(SSIM)of 0.94 in the high-frequency reconstruction of complex mouse abdominal structures.This innovative PACT system is notable for its capability to seamlessly acquire multi-bandwidth full-view PAIs,thereby advancing the application of PAI technology in the biomedical domain.
基金supported in part by the Gusu Innovation and Entrepreneurship Leading Talents in Suzhou City,grant numbers ZXL2021425 and ZXL2022476Doctor of Innovation and Entrepreneurship Program in Jiangsu Province,grant number JSSCBS20211440+6 种基金Jiangsu Province Key R&D Program,grant number BE2019682Natural Science Foundation of Jiangsu Province,grant number BK20200214National Key R&D Program of China,grant number 2017YFB0403701National Natural Science Foundation of China,grant numbers 61605210,61675226,and 62075235Youth Innovation Promotion Association of Chinese Academy of Sciences,grant number 2019320Frontier Science Research Project of the Chinese Academy of Sciences,grant number QYZDB-SSW-JSC03Strategic Priority Research Program of the Chinese Academy of Sciences,grant number XDB02060000.
文摘The prediction of fundus fluorescein angiography(FFA)images from fundus structural images is a cutting-edge research topic in ophthalmological image processing.Prediction comprises estimating FFA from fundus camera imaging,single-phase FFA from scanning laser ophthalmoscopy(SLO),and three-phase FFA also from SLO.Although many deep learning models are available,a single model can only perform one or two of these prediction tasks.To accomplish three prediction tasks using a unified method,we propose a unified deep learning model for predicting FFA images from fundus structure images using a supervised generative adversarial network.The three prediction tasks are processed as follows:data preparation,network training under FFA supervision,and FFA image prediction from fundus structure images on a test set.By comparing the FFA images predicted by our model,pix2pix,and CycleGAN,we demonstrate the remarkable progress achieved by our proposal.The high performance of our model is validated in terms of the peak signal-to-noise ratio,structural similarity index,and mean squared error.
基金support of the foundations:National Key R&D Program of China,Grant Nos.2022YFC2404201CAS Project for Young Scientists in Basic Research,Grant Nos.YSBR-067+2 种基金The Gusu Innovation and Entrepreneurship Leading Talents in Suzhou City,Grant Nos.ZXL2021425Jiangsu Science and Technology Plan Program,Grant Nos.BK20220263National Key R&D Program of China,Grant Nos.2021YFF0700503.
文摘There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma surgery.Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments.After surgery,a subjective feedback survey about the user experience was taken.The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery.The custom-made instruments also solved the shadowing problem in OCT imaging.Surgeons preferred to use the system in their future practice.
基金This work was in part supported by the International Partnership Program of Chinese Academy of Science(Grant No.154232KYSB20200016)the Suzhou Science and Technology Support Project(Grant No.SYG201905)+2 种基金the National Key Research and Development Program of China(Grant No.2020YFC2007400)H.C.acknowledges the supports provided by the National Science Foundation(NSF)(Grant No.ECCS-1933072)the National Heart,Lung,And Blood Institute of the National Institutes of Health under Award Number R61HL154215,and Penn State University.The partial support from the Center for Biodevices,the College of Engineering,and the Center for Security Research and Education at Penn State is also acknowledged.
文摘As the key component of wireless data transmission and powering,stretchable antennas play an indispensable role in flexible/stretchable electronics.However,they often suffer from frequency detuning upon mechanical deformations;thus,their applications are limited to wireless sensing with wireless transmission capabilities remaining elusive.Here,a hierarchically structured stretchable microstrip antenna with meshed patterns arranged in an arched shape showcases tunable resonance frequency upon deformations with improved overall stretchability.The almost unchanged resonance frequency during deformations enables robust on-body wireless communication and RF energy harvesting,whereas the rapid changing resonance frequency with deformations allows for wireless sensing.The proposed stretchable microstrip antenna was demonstrated to communicate wirelessly with a transmitter(input power of−3 dBm)efficiently(i.e.,the receiving power higher than−100 dBm over a distance of 100 m)on human bodies even upon 25%stretching.The flexibility in structural engineering combined with the coupled mechanical-electromagnetic simulations,provides a versatile engineering toolkit to design stretchable microstrip antennas and other potential wireless devices for stretchable electronics.
基金Project supported by Ji Hua Laboratory(Grant No.X190131TD190)the Research and Development Project for Equipment of Chinese Academy of Sciences(Grant No.YJKYYQ20210051)+1 种基金the Suzhou pilot project of basic research(Grant No.SJC2021024)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20200215)。
文摘Atomic magnetometers operated in the spin-exchange relaxation-free(SERF)regime are the promising sensor to replace superconducting quantum interference devices(SQUIDs)in the biomagnetism field.The SERF magnetometer with compact size and good performance is crucial to the new generation of wearable magnetoencephalography(MEG)system.In this paper,we developed a compact and closed-loop SERF magnetometer with the dimensions of 15.0×22.0×30.0 mm^(3)based on a single-beam configuration.The bandwidth of the magnetometer was extended to 675 Hz while the sensitivity was maintained at 22 f T/Hz^(1/2).A nearly 3-fold enhancement of the bandwidth was obtained in comparison with the open-loop control.The implementation of the closed-loop control also greatly improved the dynamic range,enabling the magnetometer to be robust against the disturbance of the ambient field.Moreover,the magnetometer was successfully applied for the detection of humanα-rhythm and auditory evoked fields(AEFs),which demonstrated the potential to be extended to multi-channel MEG measurements for future neuroscience studies.
基金Chinese Academy of Sciences MRI Technology Alliance under Grant 2020GZ1004partly by Natural Science Foundation of Shandong Province under Grant ZR2021QA091+1 种基金partly by the Major Innovative Research Team of Suzhou under Grant ZXT2019007partly by the Natural Science Foundation of Tianjin under Grant 17JCYBJC43400.
文摘With advantages of small volume,high field strength,and compact stray field,the Halbach array magnet is of great potential in desktop NMR applications.However,field inhomogeneity poses a main obstacle to its applications.Active shimming is necessary for improving the field homogeneity.An active shim coil design method for cylindrical Halbach magnet based on inverse boundary element method(iBEM)is introduced in this work.Shim coils targeting 1st~3rd and Z4/Z5/Z6 spherical harmonic(SH)terms were designed with constraints of field accuracy,resistance,inductance,and current density.Wire loops and symmetric property influence were discussed to further improve the performance of high-order shim coils.Finally,with the prototype of the shim coils constructed,field pattern and SH transformation proved that the coils designed could fit the target SH distribution,though contamination from low-order components existed in highorder terms.A practical shimming experiment on the Halbach magnet has improved the homogeneity from 40.3 ppm to 3.8 ppm in radius 2.5 mm,height 5 mm cylindrical sample space,verifying the coils'compensation ability.This work provides a flexible inverse coil design method for cylindrical Halbach magnet and discusses the high-order shim coil design and implementation,which is potential in nuclear magnetic resonance applications based on Halbach magnet arrays.
文摘Objective The detection of RNA single nucleotide polymorphism(SNP)is of great importance due to their association with protein expression related to various diseases and drug responses.At present,splintR ligase-assisted methods are important approaches for RNA direct detection,but its specificity will be limited when the fidelity of ligases is not ideal.The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection.Methods In this study,a dualcompetitive-padlock-probe(DCPLP)assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation.To verify the method,we employed dual competitive padlock probe-mediated rolling circle amplification(DCPLP-RCA)to genotype the CYP2C9 gene.Results The specificity was well improved through the competition and strand displacement of dual padlock probe,with an 83.26%reduction in nonspecific signal.By detecting synthetic RNA samples,the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L.Furthermore,clinical samples were applied to the method to evaluate its performance,and the genotyping results were consistent with those obtained using the qPCR method.Conclusion This study has successfully established a highly specific direct RNA SNP detection method,and provided a novel avenue for accurate identification of various types of RNAs.
基金supported by the National Natural Science Foundation of China(No.61675226).
文摘Objective Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus(AAV)vector encodingβ-catenin to treat AMD in a mouse model.Methods Mice were intravitreally injected with AAV2/8-Y733F-VMD2-β-catenin for 2 or 4 weeks,andβ-catenin expression was measured using immunofluorescence staining,real-time quantitative reverse transcription polymerase chain reaction(PCR),and Western blotting.The function ofβ-catenin was determined using retinal flat mounts and laser-induced damage models.Finally,the safety of AAV2/8-Y733F-VMD2-β-catenin was evaluated by multiple intravitreal injections.Results AAV2/8-Y733F-VMD2-β-catenin induced the expression ofβ-catenin in RPE cells.It activated the proliferation of RPE cells and increased cyclin D1 expression.It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells.Furthermore,it could induce apoptosis of RPE cells by increasing the expression of Trp53,Bax and caspase3 while decreasing the expression of Bcl-2.Conclusion AAV2/8-Y733F-VMD2-β-catenin increasedβ-catenin expression in RPE cells,activated RPE cell proliferation,and helped mice heal from laser-induced eye injury.Furthermore,it could induce the apoptosis of RPE cells.Therefore,it may be a safe approach for AMD treatment.
基金supported by the National Natural Science Foundation of China(Grant Nos.62005307 and 61975228).
文摘Structured illumination microscopy(SIM)is a popular and powerful super-resolution(SR)technique in biomedical research.However,the conventional reconstruction algorithm for SIM heavily relies on the accurate prior knowledge of illumination patterns and signal-to-noise ratio(SNR)of raw images.To obtain high-quality SR images,several raw images need to be captured under high fluorescence level,which further restricts SIM’s temporal resolution and its applications.Deep learning(DL)is a data-driven technology that has been used to expand the limits of optical microscopy.In this study,we propose a deep neural network based on multi-level wavelet and attention mechanism(MWAM)for SIM.Our results show that the MWAM network can extract high-frequency information contained in SIM raw images and accurately integrate it into the output image,resulting in superior SR images compared to those generated using wide-field images as input data.We also demonstrate that the number of SIM raw images can be reduced to three,with one image in each illumination orientation,to achieve the optimal tradeoff between temporal and spatial resolution.Furthermore,our MWAM network exhibits superior reconstruction ability on low-SNR images compared to conventional SIM algorithms.We have also analyzed the adaptability of this network on other biological samples and successfully applied the pretrained model to other SIM systems.
文摘Recently,a study on a 0.05 T,low-cost,low-power,and computing-driven shielding-free ultra-low-field(ULF)magnetic resonance imaging(MRI)scannerwas published.This work enhances the image quality of MRI and reduces the scanning time based on deep learning methods,which is of great significance to enhancing the popularization and availability of MRI[1](https://www.science.org/doi/abs/10.1126/science.adm7168).
基金the Natural Science Foundation of Shandong Province,No.ZR2021MH213and in part by the Suzhou Science and Technology Bureau,No.SJC2021023.
文摘Sputum smear tests are critical for the diagnosis of respiratory diseases. Automatic segmentation of bacteria from spu-tum smear images is important for improving diagnostic efficiency. However, this remains a challenging task owing to the high interclass similarity among different categories of bacteria and the low contrast of the bacterial edges. To explore more levels of global pattern features to promote the distinguishing ability of bacterial categories and main-tain sufficient local fine-grained features to ensure accurate localization of ambiguous bacteria simultaneously, we propose a novel dual-branch deformable cross-attention fusion network (DB-DCAFN) for accurate bacterial segmen-tation. Specifically, we first designed a dual-branch encoder consisting of multiple convolution and transformer blocks in parallel to simultaneously extract multilevel local and global features. We then designed a sparse and deformable cross-attention module to capture the semantic dependencies between local and global features, which can bridge the semantic gap and fuse features effectively. Furthermore, we designed a feature assignment fusion module to enhance meaningful features using an adaptive feature weighting strategy to obtain more accurate segmentation. We conducted extensive experiments to evaluate the effectiveness of DB-DCAFN on a clinical dataset comprising three bacterial categories: Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The experi-mental results demonstrate that the proposed DB-DCAFN outperforms other state-of-the-art methods and is effective at segmenting bacteria from sputum smear images.
文摘1.Introduction Light-sheet fluorescence microscopy(LSFM),since it was first coined the term selective-plane-illumination microscopy(SPIM)by Huisken et al.[1],has been developed for nearly two decades,needless to mention a landmark development of digitally scanned light-sheet microscopy(DSLM)innovated by Keller et al.[2].
基金supported in part by the National Key Research and Development Program of China,No.2022YFC2404103in part by the Jiangsu Provincial Key Research and Development Program Social Development Project,No.BE2022720+1 种基金in part by the Natural Science Foundation of China,No.62001471in part by the Suzhou Science and Technology Plan Project,No.SYG202345.
文摘Low-dose computed tomography(LDCT)has gained increasing attention owing to its crucial role in reducing radiation exposure in patients.However,LDCT-reconstructed images often suffer from significant noise and artifacts,negatively impacting the radiologists’ability to accurately diagnose.To address this issue,many studies have focused on denoising LDCT images using deep learning(DL)methods.However,these DL-based denoising methods have been hindered by the highly variable feature distribution of LDCT data from different imaging sources,which adversely affects the performance of current denoising models.In this study,we propose a parallel processing model,the multi-encoder deep feature transformation network(MDFTN),which is designed to enhance the performance of LDCT imaging for multisource data.Unlike traditional network structures,which rely on continual learning to process multitask data,the approach can simultaneously handle LDCT images within a unified framework from various imaging sources.The proposed MDFTN consists of multiple encoders and decoders along with a deep feature transformation module(DFTM).During forward propagation in network training,each encoder extracts diverse features from its respective data source in parallel and the DFTM compresses these features into a shared feature space.Subsequently,each decoder performs an inverse operation for multisource loss estimation.Through collaborative training,the proposed MDFTN leverages the complementary advantages of multisource data distribution to enhance its adaptability and generalization.Numerous experiments were conducted on two public datasets and one local dataset,which demonstrated that the proposed network model can simultaneously process multisource data while effectively suppressing noise and preserving fine structures.The source code is available at https://github.com/123456789ey/MDFTN.
基金supported by the National Key Research and Development Program of China(2021YFF0700700)the National Natural Science Foundation of China(62075235)+2 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2019320)Entrepreneurship and Innovation Talents in Jiangsu Province(Innovation of Scientific Research Institutes)the Jiangsu Provincial Key Research and Development Program(BE2019682).
文摘The widely used Shack-Hartmann wavefront sensor(SHWFS)is a wavefront measurement system.Its measurement accuracy is limited by the reference wavefront used for calibration and also by various residual errors of the sensor itself.In this study,based on the principle of spherical wavefront calibration,a pinhole with a diameter of 1μm was used to generate spherical wavefronts with extremely small wavefront errors,with residual aberrations of 1.0×10^(−4)λRMS,providing a high-accuracy reference wavefront.In the first step of SHWFS calibration,we demonstrated a modified method to solve for three important parameters(f,the focal length of the microlens array(MLA),p,the sub-aperture size of the MLA,and s,the pixel size of the photodetector)to scale the measured SHWFS results.With only three iterations in the calculation,these parameters can be determined as exact values,with convergence to an acceptable accuracy.For a simple SHWFS with an MLA of 128×128 sub-apertures in a square configuration and a focal length of 2.8 mm,a measurement accuracy of 5.0×10^(−3)λRMS was achieved across the full pupil diameter of 13.8 mm with the proposed spherical wavefront calibration.The accuracy was dependent on the residual errors induced in manufacturing and assembly of the SHWFS.After removing these residual errors in the measured wavefront results,the accuracy of the SHWFS increased to 1.0×10^(−3)λRMS,with measured wavefronts in the range ofλ/4.Mid-term stability of wavefront measurements was confirmed,with residual deviations of 8.04×10^(−5)λPV and 7.94×10^(−5)λRMS.This study demonstrates that the modified calibration method for a high-accuracy spherical wavefront generated from a micrometer-scale pinhole can effectively improve the accuracy of an SHWFS.Further accuracy improvement was verified with correction of residual errors,making the method suitable for challenging wavefront measurements such as in lithography lenses,astronomical telescope systems,and adaptive optics.