Confocal laser speckle autocorrelation imaging of dynamic flow in microvasculature

Laser speckle imaging has been widely used for in-vivo visualization of blood perfusion in biological tissues.However,existing laser speckle imaging techniques suffer from limited quantification accuracy and spatial resolution.Here we re-port a novel design and implementation of a powerful laser speckle imaging platform to solve the two critical limitations.The core technique of our platform is a combination of line scan confocal microscopy with laser speckle autocorrelation imaging,which is termed Line Scan Laser Speckle Autocorrelation Imaging(LS-LSAI).The technical advantages of LS-LSAI include high spatial resolution(~4.4μm)for visualizing and quantifying blood flow in microvessels,as well as video-rate imaging speed for tracing dynamic flow.

Advanced optical microscopy methods for in vivo imaging of sub-cellular structures in thick biological tissuesl

Optical microscopy has become an indispensable tool for visualizing sub-cellular structures andbiological processes.However,scattering in biological tissues is a major obstacle that preventshigh-resolution images from being obtained from deep regions of tissue.We review commontechniques,such as multiphoton microscopy(MPM)and optical coherence microscopy(OCM),for diffraction limited imaging beyond an imaging depth of 0.5 mm.Novel implementations havebeen emerging in recent years giving higher imaging speed,deeper penetration,and better imagequality.Focal modulation microscopy(FMM)is a novel method that combines confocal spatialfltering with focal modulation to reject out-of-focus background.FMM has demonstrated animaging depth comparable to those of MPM and OCM,near-real-time image acquisition,and thecapability for multiple contrast mechanisms.

Effect of Changing Heart Rate on the Ocular Pulse and Optic Nerve Head Deformations

Objective To study the effect of changing heart rate on the ocular pulse and optic nerve head deformations with a viscoelastic lamina cribrosa.Methods An FE model of a healthy eye was reconstructed.The choroid was biphasic and consisted of a solid phase(connective tissues)and a fluid phase(blood).The LC was viscoelastic as characterized by a stress-relaxation test.We applied arterial pressures at 18 entry sites(posterior ciliary arteries)and venous pressures at 4 exit sites(vortex veins).The heart rate was varied from 60 bpm to 120 bpm(increment:20 bpm).We reported the ocular pulse amplitude(OPA),pulse volume,optic nerve head(ONH)deformations and the dynamic modulus of the LC at different heart rates.Results With an increasing heart rate,the OPA decreased by 0.04 mmHg for every 10 bpm increase.The pulse volume also exhibited a linear relationship with heart rate,and decreased by 0.13 L.In addition,the storage modulus and the loss modulus of the LC center increased by 0.014 MPa and 0.04 MPa,respectively for every 10 pm increase in heart rate.Conclusions Our model predicted that the OPA,the pulse volume the ONH deformation decreased at a faster heartrate.We also found that the viscoelastic LC became stiffer with an increasing heart rate.Further studies are required to explore the potential links with the vascular dysregulation and axonal loss in glaucoma.

Enhancing single-cell encapsulation in droplet microfluidics with fine-tunable on-chip sample enrichment

Single-cell encapsulation in droplet microfluidics is commonly hindered by the tradeoff between cell suspension density and on-chip focusing performance.In this study,we introduce a novel droplet microfluidic chip to overcome this challenge.The chip comprises a double spiral focusing unit,a flow resistance-based sample enrichment module with fine-tunable outlets,and a crossflow droplet generation unit.Utilizing a low-density cell/bead suspension(2×10^(6) objects/mL),cells/beads are focused into a near-equidistant linear arrangement within the double spiral microchannel.The excess water phase is diverted while cells/beads remain focused and sequentially encapsulated in individual droplets.Focusing performance was assessed through numerical simulations and experiments at three flow rates(40,60,80μL/min),demonstrating successful focusing at 40 and 80μL/min for beads and cells,respectively.In addition,both simulation and experimental results revealed that the flow resistance at the sample enrichment module is adjustable by punching different outlets,allowing over 50%of the aqueous phase to be removed.YOLOv8n-based droplet detection algorithms realized the counting of cells/beads in droplets,statistically demonstrating single-cell and bead encapsulation rates of 72.2%and 79.2%,respectively.All the results indicate that this on-chip sample enrichment approach can be further developed and employed as a critical component in single-cell encapsulation in water-in-oil droplets.

A Review on Deterministic Lateral Displacement for Particle Separation and Detection

The separation and detection of particles in suspension are essential for a wide spectrum of applications including medical diagnostics.In this field,microfluidic deterministic lateral displacement(DLD)holds a promise due to the ability of continuous separation of particles by size,shape,deformability,and electrical properties with high resolution.DLD is a passive microfluidic separation technique that has been widely implemented for various bioparticle separations from blood cells to exosomes.DLD techniques have been previously reviewed in 2014.Since then,the field has matured as several physics of DLD have been updated,new phenomena have been discovered,and various designs have been presented to achieve a higher separation performance and throughput.Furthermore,some recent progress has shown new clinical applications and ability to use the DLD arrays as a platform for biomolecules detection.This review provides a thorough discussion on the recent progress in DLD with the topics based on the fundamental studies on DLD models and applications for particle separation and detection.Furthermore,current challenges and potential solutions of DLD are also discussed.We believe that a comprehensive understanding on DLD techniques could significantly contribute toward the advancements in the field for various applications.In particular,the rapid,low-cost,and high-throughput particle separation and detection with DLD have a tremendous impact for point-of-care diagnostics.

A Novel Tele-Operated Flexible Robot Targeted for Minimally Invasive Robotic Surgery

In this paper, a novel flexible robot system with a constrained tendon-driven serpentine manipulator(CTSM) is presented. The CTSM gives the robot a larger workspace, more dexterous manipulation, and controllable stiffness compared with the da Vinci surgical robot and traditional flexible robots. The robot is tele-operated using the Novint Falcon haptic device. Two control modes are implemented, direct mapping and incremental mode. In each mode, the robot can be manipulated using either the highest stiffness scheme or the minimal movement scheme. The advantages of the CTSM are shown by simulation and experimental results.

Safety evaluation of nanodiamond-doxorubicin complexes in a Naïve Beagle canine model using hematologic,histological,and urine analysis

While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models.In addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates.Before the clinical translation of NDX,it is necessary to verify the safety of ND in large mammals.Studies of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical assessment.Herein,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle dogs.The study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection methods.The dogs are monitored for their health phenotype changes in continuous 5 days.Blood and urine obtained are for clinical pathology research.The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model.This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.

Cell biomechanics and its applications in human disease diagnosis

Certain diseases are known to cause changes in the physical and biomechanical properties of cells.These include cancer,malaria,and sickle cell anemia among others.Typically,such physical property changes can result in several fold increases or decreases in cell stiffness,which are significant and can result in severe pathology and eventual catastrophic breakdown of the bodily functions.While there are developed biochemical and biological assays to detect the onset or presence of diseases,there is always a need to develop more rapid,precise,and sensitive methods to detect and diagnose diseases.Biomechanical property changes can play a significant role in this regard.As such,research into disease biomechanics can not only give us an in-depth knowledge of the mechanisms underlying disease progression,but can also serve as a powerful tool for detection and diagnosis.This article provides some insights into opportunities for how significant changes in cellular mechanical properties during onset or progression of a disease can be utilized as useful means for detection and diagnosis.We will also showcase several technologies that have already been developed to perform such detection and diagnosis.

Modular micro-PCR system for the onsite rapid diagnosis of COVID-19

Effective containment of the COVID-19 pandemic requires rapid and accurate detection of the pathogen.Polymerase chain reaction(PCR)remains the gold standard for COVID-19 confirmation.In this article,we report the performance of a cost-effective modular microfluidic reverse transcription(RT)-PCR and RT-loop mediated isothermal amplification(RTLAMP)platform,Epidax®,for the point-of-care testing and confirmation of SARS-CoV-2.This platform is versatile and can be reconfigured either for screening using endpoint RT-PCR or RT-LAMP tests or for confirmatory tests using realtime RT-PCR.Epidax®is highly sensitive and detects as little as 1 RNA copy perµL for real-time and endpoint RT-PCR,while using only half of the reagents.We achieved comparable results with those of a commercial platform when detecting SARS-CoV-2 viruses from 81 clinical RNA extracts.Epidax®can also detect SARS-CoV-2 from 44 nasopharyngeal samples without RNA extraction by using a direct RT-PCR assay,which shortens the sample-to-answer time to an hour with minimal user steps.Furthermore,we validated the technology using an RT-LAMP assay on 54 clinical RNA extracts.Overall,our platform provides a sensitive,cost-effective,and accurate diagnostic solution for lowresource settings.

Multiple Unmanned Underwater Vehicles Consensus Control with Unmeasurable Velocity Information and Environmental Disturbances Under Switching Directed Topologies

A consensus algorithm proposed in the paper is applied to tackle remarkable problems of unmeasurable velocities,the environmental disturbances, and the limited communication environment for the multiple unmanned underwater vehicles(multi-UUVs). Firstly, for a complex nonlinear and coupled model of the unmanned underwater vehicle(UUV), a technique of feedback linearization is developed to transform the nonlinear UUV model into a secondorder integral UUV model. Secondly, to address the problem of the unavailable velocity information and environmental disturbances for the multi-UUVs system, we design a distributed extended state observer(DESO) to estimate the unmeasurable velocities and environmental disturbances using the relative position information. Finally,we propose a protocol based on the estimation information from the DESO and demonstrate that the multi-UUVs system with the switching directed topologies under the protocol can reach consensus asymptotically. The theoretical result proposed in the literature is verified by one numerical example.

Printable Kirigami-inspired Flexible and Soft Anthropomorphic Robotic Hand

We present a kirigami-inspired design scheme for a robotic hand by 3D printable folds and cuts.The unique contribution is the printable flexible hand,which provides flexibility and maneuverability that is unavailable in rigid robotic systems.The integration of sensors in the robotic system enables force adjustment for robotic systems applicable in the future.The experimental results have shown that this design can perform everyday tasks through grasping and pinching different items.The fingers can bend from 40 to 100 degrees.Furthermore,the direct printable kirigami cuts and folds from soft elastic printable materials have significant potential for prosthetic devices.The printable kirigami design framework opens the possibility for future developments and modifications in numerous robotic applications.

Biomechanical analysis of the placement of fixation lag screw in different intertrochanteric hip fracture angles

The common surgical method for fracture fixation in the femoral neck and intertrochanteric region is the implantation a dynamic lag screw into the femoral head.However,failure rates of this fixation are high due to a cut-out of the lag screw from the femoral head.It is unclear if the lag screw positions will affect the stabilisation of the intertrochanteric fracture with different fracture angles.This study aimed to examine the influence of lag screw placement in the fixation of hip fractures with different fracture angles in healthy and osteoporotic femurs using three-dimensional finite element analysis.Two screw positions at the centre and inferior-posterior(IP)of the femoral head with three fracture angles(30°,45°,60°)were studied.The results showed that varying fracture angles and the onset of disease(osteoporosis)have influenced the optimal placement of the lag screw.The lag screw in the IP position in the healthy femur with 30°and 45°fracture angles and osteoporotic femur with 30°fracture angle induced lower periprosthetic bone strains.For a healthy femur with 60°fracture angle and osteoporotic bone with 45°and 60°fracture angles,a centralised placement of the lag screw in the femoral neck was preferred.

Emerging flexible and wearable physical sensing platforms for healthcare and biomedical applications

There are now numerous emerging flexible and wearable sensing technologies that can perform a myriad of physical and physiological measurements.Rapid advances in developing and implementing such sensors in the last several years have demonstrated the growing significance and potential utility of this unique class of sensing platforms.Applications include wearable consumer electronics,soft robotics,medical prosthetics,electronic skin,and health monitoring.In this review,we provide a state-ofthe-art overview of the emerging flexible and wearable sensing platforms for healthcare and biomedical applications.We first introduce the selection of flexible and stretchable materials and the fabrication of sensors based on these materials.We then compare the different solid-state and liquid-state physical sensing platforms and examine the mechanical deformation-based working mechanisms of these sensors.We also highlight some of the exciting applications of flexible and wearable physical sensors in emerging healthcare and biomedical applications,in particular for artificial electronic skins,physiological health monitoring and assessment,and therapeutic and drug delivery.Finally,we conclude this review by offering some insight into the challenges and opportunities facing this field.

How far is Lignin from being a biomedical material?

Lignin is a versatile biomass that possesses many different desirable properties such as antioxidant,antibacterial,anti-UV,and good biocompatibility.Natural lignin can be processed through several chemical processes.The processed lignin can be modified into functionalized lignin through chemical modifications to develop and enhance biomaterials.Thus,lignin is one of the prime candidate for various biomaterial applications such as drug and gene delivery,biosensors,bioimaging,3D printing,tissue engineering,and dietary supplement additive.This review presents the potential of developing and utilizing lignin in the outlook of new and sustainable biomaterials.Thereafter,we also discuss on the challenges and outlook of utilizing lignin as a biomaterial.

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties.Conventional cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers,but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected in vivo.To overcome these challenges,in this work,we describe a 3D dynamic hydrogel using magneto-stimulation for direct MSC manufacturing to therapy.With our technology,we found that dynamic mechanical stimulation(DMS)enhanced matrix-integrinβ1 interactions which induced MSCs spreading and proliferation.In addition,DMS could modulate MSC biofunctions including directing MSC differentiation into specific lineages and boosting paracrine activities(e.g.,growth factor secretion)through YAP nuclear localization and FAK-ERK pathway.With our magnetic hydrogel,complex procedures from MSC manufacturing to final clinical use,can be integrated into one single platform,and we believe this‘all-in-one’technology could offer a paradigm shift to existing standards in MSC therapy.

Soy, soil and beyond

Summary Soy and its quest for future food production.Soy,or soybean(Glycine max),is a leguminous plant that has played a significant role in various civilizations throughout human history.Soybeans are native to East Asia and have been cultivated in China for thousands of years.As a food source,soy has a wide range of uses,they include tofu,tempeh,soy milk,soy sauce,miso,soy-based meat alternatives,desserts and snacks.These products serve as alternatives to animal-based proteins and dairy products for vegetarians,vegans,and individuals with dietary restrictions.In addition,soybean oil is one of the most widely consumed cooking oils globally.It is used for frying,baking,sautéing,and salad dressings due to its mild flavour and high smoke point.Soybean oil is also used as an ingredient in margarine,mayonnaise,and other food products.

Microbial resistance to nanotechnologies:An important but understudied consideration using antimicrobial nanotechnologies in orthopaedic implants

Microbial resistance to current antibiotics therapies is a major cause of implant failure and adverse clinical outcomes in orthopaedic surgery.Recent developments in advanced antimicrobial nanotechnologies provide numerous opportunities to effective remove resistant bacteria and prevent resistance from occurring through unique mechanisms.With tunable physicochemical properties,nanomaterials can be designed to be bactericidal,antifouling,immunomodulating,and capable of delivering antibacterial compounds to the infection region with spatiotemporal accuracy.Despite its substantial advancement,an important,but under-explored area,is potential microbial resistance to nanomaterials and how this can impact the clinical use of antimicrobial nanotechnologies.This review aims to provide a better understanding of nanomaterial-associated microbial resistance to accelerate bench-to-bedside translations of emerging nanotechnologies for effective control of implant associated infections.