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.

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.

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.

Collagen 1 signaling at the central nervous system injury site and astrogliosis

Central nervous system （CNS） injuries are often devastating as func- tional recovery via axonal regrowth over the lesion site is very minimal.

Regeneration from a Cell Biological Perspective—Fascinating New Insights and Paradigms

Regeneration research is more focused on translational values. However, lying at its very foundation is an understanding of how tissues and organs repair and renew themselves at the cellular level. The past decade has witnessed paradigm changing advances in regenerative biology, many of these stems from novel insights into stemness, pluripotency, cell death and their related intra- and inter-cellular biochemical and molecular processes. Some of these new insights are highlighted in the paragraphs that follow. We now have a much better understanding of how regeneration occurs in lower organisms. We have also discovered tools and means of nuclear reprogramming to generate induced pluripotency and changes in cell fate in mammalian models. With further research, there is reasonable hope that various obstacles of regeneration in humans can be better understood and tackled. As regeneration research enters a new era, CellBio welcomes timely review articles and original papers on the theme of “The Cell Biology of Regeneration”.

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.

Triboelectric Nanogenerators and Hybridized Systems for Enabling Next-Generation IoT Applications

In the past few years,triboelectric nanogenerator-based(TENG-based)hybrid generators and systems have experienced a widespread and flourishing development,ranging among almost every aspect of our lives,e.g.,from industry to consumer,outdoor to indoor,and wearable to implantable applications.Although TENG technology has been extensively investigated for mechanical energy harvesting,most developed TENGs still have limitations of small output current,unstable power generation,and low energy utilization rate of multisource energies.To harvest the ubiquitous/coexisted energy forms including mechanical,thermal,and solar energy simultaneously,a promising direction is to integrate TENG with other transducing mechanisms,e.g.,electromagnetic generator,piezoelectric nanogenerator,pyroelectric nanogenerator,thermoelectric generator,and solar cell,forming the hybrid generator for synergetic single-source and multisource energy harvesting.The resultant TENG-based hybrid generators utilizing integrated transducing mechanisms are able to compensate for the shortcomings of each mechanism and overcome the above limitations,toward achieving a maximum,reliable,and stable output generation.Hence,in this review,we systematically introduce the key technologies of the TENG-based hybrid generators and hybridized systems,in the aspects of operation principles,structure designs,optimization strategies,power management,and system integration.The recent progress of TENG-based hybrid generators and hybridized systems for the outdoor,indoor,wearable,and implantable applications is also provided.Lastly,we discuss our perspectives on the future development trend of hybrid generators and hybridized systems in environmental monitoring,human activity sensation,human-machine interaction,smart home,healthcare,wearables,implants,robotics,Internet of things(IoT),and many other fields.

Upconversion Nanoparticles-Encoded Hydrogel Microbeads-Based Multiplexed Protein Detection

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.

Deep learning-enabled triboelectric smart socks for IoT-based gait analysis and VR applications

The era of artificial intelligence and internet of things is rapidly developed by recent advances in wearable electronics.Gait reveals sensory information in daily life containing personal information,regarding identification and healthcare.Current wearable electronics of gait analysis are mainly limited by high fabrication cost,operation energy consumption,or inferior analysis methods,which barely involve machine learning or implement nonoptimal models that require massive datasets for training.Herein,we developed low-cost triboelectric intelligent socks for harvesting waste energy from low-frequency body motions to transmit wireless sensory data.The sock equipped with self-powered functionality also can be used as wearable sensors to deliver information,regarding the identity,health status,and activity of the users.To further address the issue of ineffective analysis methods,an optimized deep learning model with an end-to-end structure on the socks signals for the gait analysis is proposed,which produces a 93.54%identification accuracy of 13 participants and detects five different human activities with 96.67%accuracy.Toward practical application,we map the physical signals collected through the socks in the virtual space to establish a digital human system for sports monitoring,healthcare,identification,and future smart home applications.

Mitochondrial homeostasis in Parkinson＇s disease-a triumvirate rule？

Mitochondrial dysfunction in Parkinson＇s disease：Mitochondria are the primary energy generator of the cell and they are important for cell survival and apoptosis.Defective mitochondrial homeostasis is frequently reported in human diseases especially those affecting the brain.

3D Printing of Next-generation Electrochemical Energy Storage Devices: from Multiscale to Multimaterial

The increasing energy requirements to power the modern world has driven active research into more advanced electrochemical energy storage devices(EESD)with both high energy densities and power densities.Wide range of newly discovered materials with promising electrochemical properties has shown great potential for next-generation devices,but their performance is normally associated with contradicting demands of thin electrodes and high mass loading that can be hardly achieved for practical applications.Design of three-dimensional(3D)porous electrodes can increase the mass loading while maintaining the effective charge transport even with thick electrodes,which has proven to be efficient to overcome the limitations.3D structures have also been demonstrated excellent structural stability to withstand strong strains and stresses generated during charge/discharge cycle.3D printing,which can fabricate various delicate and complex structural designs,thus offering brand-new opportunities for the rational design and facile construction of next-generation EESDs.The recent developments in 3D printing of next-generation EESDs with high performance are reviewed.Advanced/multiscale electrode structures,such as hierarchically porous structure that can be constructed via high-resolution 3D printing or with post-treatment,are further emphasized.The ability of current 3D printing techniques to fulfill multimaterial printing to fulfill simple packaging will be covered.

Combating the Coronavirus Pandemic:Early Detection,Medical Treatment,and a Concerted Effort by the Global Community

The World Health Organization(WHO)has declared the outbreak of 2019 novel coronavirus,known as 2019-nCoV,a pandemic,as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fatalities as of April 23,2020.Coronavirus disease 2019(COVID-19)causes a respiratory illness with symptoms such as dry cough,fever,sudden loss of smell,and,in more severe cases,difficulty breathing.To date,there is no specific vaccine or treatment proven effective against this viral disease.Early and accurate diagnosis of COVID-19 is thus critical to curbing its spread and improving health outcomes.Reverse transcription-polymerase chain reaction(RT-PCR)is commonly used to detect the presence of COVID-19.Other techniques,such as recombinase polymerase amplification(RPA),loopmediated isothermal amplification(LAMP),clustered regularly interspaced short palindromic repeats(CRISPR),and microfluidics,have allowed better disease diagnosis.Here,as part of the effort to expand screening capacity,we review advances and challenges in the rapid detection of COVID-19 by targeting nucleic acids,antigens,or antibodies.We also summarize potential treatments and vaccines against COVID-19 and discuss ongoing clinical trials of interventions to reduce viral progression.

Expanding chiral metamaterials for retrieving fingerprints via vibrational circular dichroism

Circular dichroism(CD)spectroscopy has been widely demonstrated for detecting chiral molecules.However,the determination of chiral mixtures with various concentrations and enantiomeric ratios can be a challenging task.To solve this problem,we report an enhanced vibrational circular dichroism(VCD)sensing platform based on plasmonic chiral metamaterials,which presents a 6-magnitude signal enhancement with a selectivity of chiral molecules.Guided by coupled-mode theory,we leverage both in-plane and out-of-plane symmetry-breaking structures for chiral metamaterial design enabled by a two-step lithography process,which increases the near-field coupling strengths and varies the ratio between absorption and radiation loss,resulting in improved chiral light-matter interaction and enhanced molecular VCD signals.Besides,we demonstrate the thin-film sensing process of BSA andβ-lactoglobulin proteins,which contain secondary structures a-helix andβ-sheet and achieve a limit of detection down to zeptomole level.Furthermore,we also,for the first time,explore the potential of enhanced VCD spectroscopy by demonstrating a selective sensing process of chiral mixtures,where the mixing ratio can be successfully differentiated with our proposed chiral metamaterials.Our findings improve the sensing signal of molecules and expand the extractable information,paving the way toward label-free,compact,small-volume chiral molecule detection for stereochemical and clinical diagnosisapplications.

Mobile augmented reality visualization and collaboration techniques for on-site finite element structural analysis

In this paper,a mobile augmented reality(AR)framework for on-site finite element analysis(FEA)is proposed.The proposed framework is achieved using a client–server architecture.The performance of FEA relies on several important components,namely,computational power,visualization technique,and numerical analysis.AR renders intuitive computer-generated contents directly on a user’s surroundings.Integrating FEA with AR helps users through enhancing their perception and interaction with the engineering problems.Correct and effective visualization of these data using an AR platform can reduce the misinterpretation in spatial and logical aspects.Over the past decade,AR has undergone a transition from desktop to phablet computing.Mobile platforms enable user exploration of FEA results in situ.The client side uses a hybrid method to visualize FEA results in the mobile AR environment.In addition,a user can collaborate with other users by using the result sharing function.A prototype with basic functions has been built and a case study has been implemented to demonstrate the visualization method and evaluate the overall performance.

Fitness profiling links topoisomeraseⅡregulation of centromeric integrity to doxorubicin resistance in fission yeast

OBJECTIVE To address the molecular implication of Top2 in the context of its interaction with doxorubicin resistance(DXR)genes.METHODS To perform epistasis analyses of top2 with 63genes representing doxorubicin resistance(DXR)genes in fission yeast.Fission yeast cells with single and double mutants were serial diluted and spotted to plates containing 15-75μg·mL-1 doxorubicin.Plates were scanned after 3and 7d.Cell growth was measured and compared between single mutants and double mutants.Nucleus morphology was performed by staining the cells with 4′,6-diamidino-2-phenylindole(DAPI)to observe chromosome segregation.Reverse transcriptase PCR(RT-PCR)was employed to visualize the changes in transcription level and evaluate the stability of chromatin structure.RESULTS Our findings revealed a subset that synergistically collaborate with Top2 to confer DXR and showed that the chromatin-regulating RSC and SAGA complexes act with Top2 in a cluster that is functionally distinct from the Ino80 complex.In various DXR mutants,doxorubicin hypersensitivity was unexpectedly suppressed by a concomitant top2 mutation.Several DXR proteins showed centromeric localization,and their disruption resulted in centromeric defects and chromosome missegregation.An additional top2 mutation could restore centromeric chromatin integrity,suggesting a counterbalance between Top2 and these DXR factors in conferring doxorubicin resistance.CONCLUSION The findings reported here show a functional interaction between Top2 and factors that confer genomic stability at centromeric chromatin under doxorubicin condition.Overall,this molecular basis for mitotic catastrophe associated with doxorubicin treatment will help to facilitate drug combinatorial usage in Doxorubicin-related chemotherapeutic regimens.

Discovery of novel thieno[3,2-b]pyrrole 5-carboxamides as potent inhibitors of Chikungunya virus

Chikungunya fever(CHIKF)is an arboviral disease that typically consists of an acute illness with fever,skin rash,and incapacitating arthralgia.The causative agent of CHIKF is Chikungunya virus(CHIKV),an alphavirus that is transmitted by the Aedes mosquitoes.Despite the re-emergence of CHIKV as an epidemic threat,there is no approved effective anti-viral treatment currently available for CHIKV.In our preliminary studies,selected small molecule inhibitors of arboviruses related to CHIKV were investigated and this led us to identify compounds with thieno[3,2-b]pyrrole scaffold as hits.Building on the discovery of our best hit compounds,5-carboxylic acid thieno[3,2-b]pyrrole 1 and 5-carboxamide thieno[3,2-b]pyrrole 2,the main aim of this study is to optimize their anti-viral activities by synthesizing analogs of thieno[3,2-b]pyrroles 1 and 2 and examine their activities against CHIKV.In these two parallel optimization studies,we synthesized two series of thieno[3,2-b]pyrroles,namely the 5-carboxylic acids and 5-carboxamides that possessed a variety of substituents at N4,C2,C6 or C5positions of the thieno[3,2-b]pyrrole scaffold.These compounds were then examined for their cytotoxicity effects and anti-viral activities using a luminescence-labelled CHIKV infectious clone.The most potent compound in our studies was found in the 5-carboxamide series.The synthesis,biological activity and structure-activity relationship(SAR)will be presented and discussed in detail.

Synthetic Spin-Orbit Coupling in Two-Level Cold Atoms

We theoretically and computationally show the simplest realization of SOC using two-level cold atoms interacting with only one laser beam.The underlying mechanism is based on the non-adiabatic nature of laser-atom interaction,with the Rabi frequency being not much larger than the kinetic energy of the atom.We use Zitterbewegung oscillation to further illustrate the effects of the synthesized SOC on the quantum dynamics of the two-level cold atoms.We expect our proposal to be of experimental interest in the quantum simulation of SOC-related physics.

Emerging liver organoid platforms andtechnologies

Building human organs in a dish has been a long term goal of researchers in pursue of physiologically relevantmodels of human disease and for replacement of worn out and diseased organs. The liver has been an organ ofinterest for its central role in regulating body homeostasis as well as drug metabolism. An accurate liver replicashould contain the multiple cell types found in the organ and these cells should be spatially organized to resembletissue structures. More importantly, the in vitro model should recapitulate cellular and tissue level functions.Progress in cell culture techniques and bioengineering approaches have greatly accelerated the development ofadvance 3-dimensional (3D) cellular models commonly referred to as liver organoids. These 3D models describedrange from single to multiple cell type containing cultures with diverse applications from establishing patientspecificliver cells to modeling of chronic liver diseases and regenerative therapy. Each organoid platform isadvantageous for specific applications and presents its own limitations. This review aims to provide acomprehensive summary of major liver organoid platforms and technologies developed for diverse applications.

Galactose functionalized diketopyrrolopyrrole as NIR fluorescent probes for lectin detection and Hep G2 cell targeting based on aggregation-induced emission mechanism

Since the elucidation that sugar-lectin interactions contribute to the understanding of ‘‘Glycomics' ', how to construct glycosensors with rapid response, excellent sensitivity and selectivity is of intense research interest. Herein, we report the design of three NIR emissive glyco-probes based on diketopyrrolopyrrole(DPPs) conjugated with two(DPPG), four(DPPF-G) and six(DPPS-G) galactose groups. All three molecules could probe lectins with excellent sensitivity and selectivity. The increase of glyco-DPP emission in NIR region upon interaction with lectin is due to the aggregates formation induced by sugar-lectin interactions, which have been verified by dynamic light scattering(DLS) and scanning electronic microscope(SEM) analysis.Due to the multiple glyco-ligands on DPPS-G, it has been successfully used to stain Hep G2 cells through interactions between galactose and asialogly-coprotein(ASGP-R), which are overexpressed on the surface of Hep G2 cells.

Optical manipulation from the microscale to the nanoscale: fundamentals, advances and prospects

Since the invention of optical tweezers,optical manipulation has advanced significantly in scientific areas such as atomic physics,optics and biological science.Especially in the past decade,numerous optical beams and nanoscale devices have been proposed to mechanically act on nanoparticles in increasingly precise,stable and flexible ways.Both the linear and angular momenta of light can be exploited to produce optical tractor beams,tweezers and optical torque from the microscale to the nanoscale.Research on optical forces helps to reveal the nature of light–matter interactions and to resolve the fundamental aspects,which require an appropriate description of momenta and the forces on objects in matter.In this review,starting from basic theories and computational approaches,we highlight the latest optical trapping configurations and their applications in bioscience,as well as recent advances down to the nanoscale.Finally,we discuss the future prospects of nanomanipulation,which has considerable potential applications in a variety of scientific fields and everyday life.