Simultaneous Manipulation Research Articles

A Generic Transformation Approach for Complex Laboratory Data Using the Fast Healthcare Interoperability Resources Mapping Language: Method Development and Implementation.

Reaching meaningful interoperability between proprietary health care systems is a ubiquitous task in medical informatics, where communication servers are traditionally used for referring and transforming data from the source to target systems. The Mirth Connect Server, an open-source communication server, offers, in addition to the exchange functionality, functions for simultaneous manipulation of data. The standard Fast Healthcare Interoperability Resources (FHIR) has recently become increasingly prevalent in national health care systems. FHIR specifies its own standardized mechanisms for transforming data structures using StructureMaps and the FHIR mapping language (FML). In this study, a generic approach is developed, which allows for the application of declarative mapping rules defined using FML in an exchangeable manner. A transformation engine is required to execute the mapping rules. FHIR natively defines resources to support the conversion of instance data, such as an FHIR StructureMap. This resource encodes all information required to transform data from a source system to a target system. In our approach, this information is defined in an implementation-independent manner using FML. Once the mapping has been defined, executable Mirth channels are automatically generated from the resources containing the mapping in JavaScript format. These channels can then be deployed to the Mirth Connect Server. The resulting tool is called FML2Mirth, a Java-based transformer that derives Mirth channels from detailed declarative mapping rules based on the underlying StructureMaps. Implementation of the translate functionality is provided by the integration of a terminology server, and to achieve conformity with existing profiles, validation via the FHIR validator is built in. The system was evaluated for its practical use by transforming Labordatenträger version 2 (LDTv.2) laboratory results into Medical Information Object (Medizinisches Informationsobjekt) laboratory reports in accordance with the National Association of Statutory Health Insurance Physicians' specifications and into the HL7 (Health Level Seven) Europe Laboratory Report. The system could generate complex structures, but LDTv.2 lacks some information to fully comply with the specification. The tool for the auto-generation of Mirth channels was successfully presented. Our tests reveal the feasibility of using the complex structures of the mapping language in combination with a terminology server to transform instance data. Although the Mirth Server and the FHIR are well established in medical informatics, the combination offers space for more research, especially with regard to FML. Simultaneously, it can be stated that the mapping language still has implementation-related shortcomings that can be compensated by Mirth Connect as a base technology.

Terahertz beam shaping using space-time phase-only coded metasurfaces

Digital metasurfaces as space-coded surfaces composed of a set of sub-wavelength meta-atoms enable extraordinary capabilities to manipulate electromagnetic waves. Recently, amplitude-phase-joint-coding metasurfaces have been proposed to achieve enhanced beam shaping. However, design of a unit cell structure with a full manipulation of amplitude and phase of the reflected beam is challenging and this kind of unit cell structures are complicated. This paper proposes a space-time phase-only metasurface based on simple graphene-based unit cell that is digitally coded and arranged with a specific time sequence, allowing the effective simultaneous manipulation of both phase and amplitude. In this way, it is demonstrated that the terahertz beam can be shaped using the proposed metasurface.

Speech-mediated manipulation of da Vinci surgical system for continuous surgical flow

AbstractWith the advent of robot-assisted surgery, user-friendly technologies have been applied to the da Vinci surgical system (dVSS), and their efficacy has been validated in worldwide surgical fields. However, further improvements are required to the traditional manipulation methods, which cannot control an endoscope and surgical instruments simultaneously. This study proposes a speech recognition control interface (SRCI) for controlling the endoscope via speech commands while manipulating surgical instruments to replace the traditional method. The usability-focused comparisons of the newly proposed SRCI-based and the traditional manipulation method were conducted based on ISO 9241-11. 20 surgeons and 18 novices evaluated both manipulation methods through the line tracking task (LTT) and sea spike pod task (SSPT). After the tasks, they responded to the globally reliable questionnaires: after-scenario questionnaire (ASQ), system usability scale (SUS), and NASA task load index (TLX). The completion times in the LTT and SSPT using the proposed method were 44.72% and 26.59% respectively less than the traditional method, which shows statistically significant differences (p < 0.001). The overall results of ASQ, SUS, and NASA TLX were positive for the proposed method, especially substantial reductions in the workloads such as physical demands and efforts (p < 0.05). The proposed speech-mediated method can be a candidate suitable for the simultaneous manipulation of an endoscope and surgical instruments in dVSS-used robotic surgery. Therefore, it can replace the traditional method when controlling the endoscope while manipulating the surgical instruments, which contributes to enabling the continuous surgical flow in operations consequentially.

Nonlinear geometric phase coded ferroelectric nematic fluids for nonlinear soft-matter photonics

Simultaneous manipulation of multiple degrees of freedom of light lies at the heart of photonics. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting incident light into beams of new frequencies with spatially varied phase, amplitude, and angular momenta. Nevertheless, the reconfigurable control over structured light fields for advanced multimode nonlinear photonics remains a grand challenge. Here, we propose the concept of nonlinear geometric phase in an emerging ferroelectric nematic fluid, of which the second-order nonlinear susceptibility carries spin-dependent nonlinearity phase. A case study with photopatterned q-plates demonstrates the generation of second-harmonic optical vortices with spin-locked topological charges by using cascaded linear and nonlinear optical spin-orbit interactions. Furthermore, we present the dynamic tunability of second-harmonic structured light through temperature, electric field, and twisted elastic force. The proposed strategy opens new avenues for reconfigurable nonlinear photonics, with potential applications in optical communications, quantum computing, high-resolution imaging, etc.

Microscale Flow Control and Droplet Generation Using Arduino-Based Pneumatically-Controlled Microfluidic Device.

Microfluidics are crucial for managing small-volume analytical solutions for various applications, such as disease diagnostics, drug efficacy testing, chemical analysis, and water quality monitoring. The precise control of flow control devices can generate diverse flow patterns using pneumatic control with solenoid valves and a microcontroller. This system enables the active modulation of the pneumatic pressure through Arduino programming of the solenoid valves connected to the pressure source. Additionally, the incorporation of solenoid valve sets allows for multichannel control, enabling simultaneous creation and manipulation of various microflows at a low cost. The proposed microfluidic flow controller facilitates accurate flow regulation, especially through periodic flow modulation beneficial for droplet generation and continuous production of microdroplets of different sizes. Overall, we expect the proposed microfluidic flow controller to drive innovative advancements in technology and medicine owing to its engineering precision and versatility.

Enhanced efficiency and stability of perovskite solar cells through nanoimprinting dual-functional nanostructured PEAI/2D/3D perovskite interface

Using 2D perovskite for interface passivation and micro-nanostructures for light harvesting have emerged as highly effective strategies to enhance the electronic and optical performance of perovskite solar cells (PSCs) respectively. However, simultaneously achieving electronic and optical manipulation remains a challenge that holds significant importance in improving the efficiency and stability of PSCs. Here, we employed thermal imprinting to fabricate dual-functional nanostructured PEAI/2D/3D interface, which effectively passivates perovskite surface imperfections by 2D perovskites and enhances light absorption by periodic nanostructures. The simultaneous electronic and optical manipulation leads to a significant improvement in both efficiency and long-term stability. The PSCs with the dual-functional interface show a high power conversion efficiency (PCE) of 22.45 % and retain 90 % of their initial PCE after exposure to an 85 °C N2 atmosphere for 550 h.

Spatiotemporal hologram

Spatiotemporal structured light has opened up new avenues for optics and photonics. Current spatiotemporal manipulation of light mostly relies on phase-only devices such as liquid crystal spatial light modulators to generate spatiotemporal optical fields with unique photonic properties. However, simultaneous manipulation of both amplitude and phase of the complex field for the spatiotemporal light is still lacking, limiting the diversity and richness of achievable photonic properties. In this work, a simple and versatile spatiotemporal holographic method that can arbitrarily sculpt the spatiotemporal light is presented. The capabilities of this simple yet powerful method are demonstrated through the generation of fundamental and higher-order spatiotemporal Bessel wavepackets, spatiotemporal crystal-like and quasi-crystal-like structures, and spatiotemporal flat-top wavepackets. Fully customizable spatiotemporal wavepackets will find broader application in investigating the dynamics of spatiotemporal fields and interactions between ultrafast spatiotemporal pulses and matters, unveiling previously hidden light-matter interactions and unlocking breakthroughs in photonics and beyond.

Flexible and simultaneous multi-scale bioparticle manipulation to actuate cell and drug delivery utilizing AC electrokinetic -powered microswimmer

Bioparticle trapping and transporting are essential processes for developing an integrated cell and drug delivery system. Herein, we present a unique platform that effectively combines magnetic field and alternating current (AC) electrokinetics for the simultaneous manipulation of bioparticles across scales. The magnetic field is used to control the moving direction of Janus swimmers, and the AC electrokinetics incorporating dielectrophoresis (DEP) and induced charge electroosmosis (ICEO) flow are utilized to power Janus swimmers to manipulate bioparticles. Numerical characterization of the stagnant regions generated by DEP and ICEO elucidates the trapping mechanisms for both micro and nano bioparticles. We demonstrate that the Janus swimmers are capable of navigating along varied trajectories at speeds of up to hundreds of micrometers per second. Developed phase maps, derived from AC frequency and medium conductivity parameters, delineate three distinct bioparticle loading positions, offering a versatile guide for the manipulation of cells and nanodrugs. The platform’s adaptability is further highlighted by its success in performing mobile trapping of cells and nanodrugs along user-defined trajectories, targeted trapping of nanoparticle aggregations, and simultaneous multi-scale bioparticle capture. The presented multi-scale bioparticle trapping strategy, together with its unique features of simple geometric configuration, facile operation and broad applicability, can broaden utility in cellular and pharmaceutical research.

Tensing Flipper: Photosensitized Manipulation of Membrane Tension, Lipid Phase Separation, and Raft Protein Sorting in Biological Membranes.

The lateral organization of proteins and lipids in the plasma membrane is fundamental to regulating a wide range of cellular processes. Compartmentalized ordered membrane domains enriched with specific lipids, often termed lipid rafts, have been shown to modulate the physicochemical and mechanical properties of membranes and to drive protein sorting. Novel methods and tools enabling the visualization, characterization, and/or manipulation of membrane compartmentalization are crucial to link the properties of the membrane with cell functions. Flipper, a commercially available fluorescent membrane tension probe, has become a reference tool for quantitative membrane tension studies in living cells. Here, we report on a so far unidentified property of Flipper, namely, its ability to photosensitize singlet oxygen (1O2) under blue light when embedded into lipid membranes. This in turn results in the production of lipid hydroperoxides that increase membrane tension and trigger phase separation. In biological membranes, the photoinduced segregated domains retain the sorting ability of intact phase-separated membranes, directing raft and nonraft proteins into ordered and disordered regions, respectively, in contrast to radical-based photo-oxidation reactions that disrupt raft protein partitioning. The dual tension reporting and photosensitizing abilities of Flipper enable simultaneous visualization and manipulation of the mechanical properties and lateral organization of membranes, providing a powerful tool to optically control lipid raft formation and to explore the interplay between membrane biophysics and cell function.

Interactive effects of temperature and salinity on metabolism and activity of the copepod Tigriopus californicus.

In natural environments, two or more abiotic parameters often vary simultaneously, and interactions between co-varying parameters frequently result in unpredictable, non-additive biological responses. To better understand the mechanisms and consequences of interactions between multiple stressors, it is important to study their effects on not only fitness (survival and reproduction) but also performance and intermediary physiological processes. The splash-pool copepod Tigriopus californicus tolerates extremely variable abiotic conditions and exhibits a non-additive, antagonistic interaction resulting in higher survival when simultaneously exposed to high salinity and acute heat stress. Here, we investigated the response of T. californicus in activity and oxygen consumption under simultaneous manipulation of salinity and temperature to identify whether this interaction also arises in these sublethal measures of performance. Oxygen consumption and activity rates decreased with increasing assay salinity. Oxygen consumption also sharply increased in response to acute transfer to lower salinities, an effect that was absent upon transfer to higher salinities. Elevated temperature led to reduced rates of activity overall, resulting in no discernible impact of increased temperature on routine metabolic rates. This suggests that swimming activity has a non-negligible effect on the metabolic rates of copepods and must be accounted for in metabolic studies. Temperature also interacted with assay salinity to affect activity, and with acclimation salinity to affect routine metabolic rates upon acute salinity transfer, implying that the sublethal impacts of these co-varying factors are also not predictable from experiments that study them in isolation.

AI-powered modular and general-purpose droplet processing system based on single-sided continuous optoelectrowetting chip

Single-sided continuous optoelectrowetting (SCOEW) is a versatile light-controlled digital microfluidic technology. However, the absence of automated algorithms for generating light patterns to manipulate droplets has constrained SCOEW chips to employing only pre-recorded sequences. This limitation hinders SCOEW platforms in effectively addressing common experimental challenges like droplet pinning. To overcome this issue, we have developed a set of algorithms for the automatic generation of droplet-driving light patterns. By integrating these algorithms with machine vision (using YOLOv3) to detect, locate, and classify droplets through video camera input, and employing a path-planning algorithm (A*) to optimize droplet trajectories, our system achieves intelligent functionalities. These include simultaneous manipulation of multiple droplets, automated merging based on color-coded droplet composition, obstacle avoidance, and resolution of potential droplet manipulation failures (such as droplet pinning). In a practical application, we implemented an intelligent loop-mediated isothermal amplification (LAMP) assay on the platform. This modular approach to droplet processing is easily adaptable to other SCOEW hardware, offering potential integration of customizable functionality. The result is a promising suite of portable tools for a variety of biochemical analysis application.

Simultaneous Manipulation of Membrane Enthalpy and Entropy Barriers towards Superior Ion Separations

AbstractSub‐nanoporous membranes with ion selective transport functions are important for energy utilization, environmental remediation, and fundamental bioinspired engineering. Although mono/multivalent ions can be separated by monovalent ion selective membranes (MISMs), the current theory fails to inspire rapid advances in MISMs. Here, we apply transition state theory (TST) by regulating the enthalpy barrier (ΔH) and entropy barrier (ΔS) for designing next‐generation monovalent cation exchange membranes (MCEMs) with great improvement in ion selective separation. Using a molecule‐absorbed porous material as an interlayer to construct a denser selective layer can achieve a greater absolute value of ΔS for Li+ and Mg2+ transport, greater ΔH for Mg2+ transport and lower ΔH for Li+ transport. This recorded performance with a Li+/Mg2+ perm‐selectivity of 25.50 and a Li+ flux of 1.86 mol ⋅ m−2 ⋅ h−1 surpasses the contemporary “upper bound” plot for Li+/Mg2+ separations. Most importantly, our synthesized MCEM also demonstrates excellent operational stability during the selective electrodialysis (S‐ED) processes for realizing scalability in practical applications.

Simultaneous Manipulation of Membrane Enthalpy and Entropy Barriers towards Superior Ion Separations.

Sub-nanoporous membranes with ion selective transport functions are important for energy utilization, environmental remediation, and fundamental bioinspired engineering. Although mono/multivalent ions can be separated by monovalent ion selective membranes (MISMs), the current theory fails to inspire rapid advances in MISMs. Here, we apply transition state theory (TST) by regulating the enthalpy barrier (ΔH) and entropy barrier (ΔS) for designing next-generation monovalent cation exchange membranes (MCEMs) with great improvement in ion selective separation. Using a molecule-absorbed porous material as an interlayer to construct a denser selective layer can achieve a greater absolute value of ΔS for Li+ and Mg2+ transport, greater ΔH for Mg2+ transport and lower ΔH for Li+ transport. This recorded performance with a Li+/Mg2+ perm-selectivity of 25.50 and a Li+ flux of 1.86 mol ⋅ m-2 ⋅ h-1 surpasses the contemporary "upper bound" plot for Li+/Mg2+ separations. Most importantly, our synthesized MCEM also demonstrates excellent operational stability during the selective electrodialysis (S-ED) processes for realizing scalability in practical applications.

AB043. BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression.

Glioblastoma multiforme (GBM) poses significant challenges in treatment due to its aggressive nature and immune escape mechanisms. Despite recent advances in immune checkpoint blockade therapies, GBM prognosis remains poor. The role of bromodomain and extraterminal domain protein 4 (BRD4) in GBM, especially its interaction with immune checkpoints, is not well understood. Bioinformatic gene expression and survival analysis for BRD4 was utilized in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Clone formation assay, Transwell, Cell Counting Kit-8 (CCK8), and wound healing assay were utilized to validate BRD4's promotion of glioma cell proliferation, invasion, and migration. Chromatin immunoprecipitation (ChIP) assay was conducted to confirm BRD4 binding to the programmed death ligand 1 (PD-L1) promoter. A co-culture model was utilized with activated cluster of differentiation 8 (CD8)+ T cells and glioma cells. GL261 cells with BRD4 short hairpin RNA (shRNA) and/or PD-L1 cDNA were intracranially injected into mice to investigate tumor growth and survival time. Tumor tissue characteristics were analyzed using hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining and immune cell infiltration were assessed by flow cytometry. Bioinformatics analyses reveal elevated BRD4 expression in high-grade gliomas, correlating with poor patient survival. In vitro studies confirm that BRD4 promotes proliferation, invasion, and migration in GBM cells. BRD4 is a regulator of PD-L1 at the transcriptional level, implying its involvement in GBM's immune escape mechanisms. Co-culture experiments with CD8+ T cells demonstrate that BRD4 inhibition enhances tumor cell apoptosis. In vivo studies indicate that BRD4 knockout reduces immunosuppression, improves prognosis. Simultaneous manipulation of BRD4 and PD-L1 levels provides insights into their intertwined roles in shaping the immune landscape of GBM. BRD4 has the capability to regulate the growth of glioblastoma and enhance immune suppression by promoting PD-L1 expression. Targeting BRD4 represents a promising direction for future research and treatment.

Multidimensional Encryption by Chip-Integrated Metasurfaces.

Facing the challenge of information security in the current era of information technology, optical encryption based on metasurfaces presents a promising solution to this issue. However, most metasurface-based encryption techniques rely on limited decoding keys and struggle to achieve multidimensional complex encryption. It hinders the progress of optical storage capacity and puts encryption security at a disclosing risk. Here, we propose and experimentally demonstrate a multidimensional encryption system based on chip-integrated metasurfaces that successfully incorporates the simultaneous manipulation of three-dimensional optical parameters, including wavelength, direction, and polarization. Hence, up to eight-channel augmented reality (AR) holograms are concealed by near- and far-field fused encryption, which can only be extracted by correctly providing the three-dimensional decoding keys and then vividly exhibit to the authorizer with low crosstalk, high definition, and no zero-order speckle noise. We envision that the miniature chip-integrated metasurface strategy for multidimensional encryption functionalities promises a feasible route toward the encryption capacity and information security enhancement of the anticounterfeiting performance and optically cryptographic storage.

Full-Dimensional Geometric-Phase Spatial Light Metamodulation.

Full-dimensional spatial light modulation requires simultaneous, arbitrary, and independent manipulation of the spatial phase, amplitude, and polarization. This is crucial for leveraging the complete physical dimension resources of light. However, full-dimensional metamodulation can be challenging due to the need for multiple independent control factors. To address this challenge, here we propose parallel-tasking metasurfaces to enable full-dimensional spatial light metamodulation based fully on the geometric-phase concept. Indeed, the meta-atoms are divided into several subphases, each of which serves as an independent control factor to manipulate light phase, amplitude, and polarization through geometric phase, interference, and orthogonal polarization superposition, respectively. Therefore, the macroscopic group of meta-atoms leads to metasurfaces that can achieve broadband full-dimensional spatial light metamodulation, as demonstrated by various types of structured light generation. This approach paves the way to future wide applications of light manipulation enabled by full-dimensional spatial light metamodulation.

An atomic force microscopy and total internal reflection fluorescence microscopy correlated system (AFM-TIRF) for fluorescence imaging and spectroscopy of a single particle.

Combining atomic force microscopy (AFM) with other optical microscopic techniques is pivotal in nanoscale investigations, particularly leveraging the surface-sensitive properties of total internal reflection fluorescence microscopy (TIRF). A novel design that integrates AFM with a multi-wavelength TIRF is displayed, providing simultaneous fluorescence imaging and spectral acquisition capabilities. We elaborate on the considerations in the instrument design process and demonstrate the performance and potential applications of the instrument through fluorescence imaging and spectroscopy testing of individual nanoparticles. This AFM and TIRF correlated system (AFM-TIRF) emerges as a promising option for single-molecule fluorescence studies, enabling simultaneous manipulation and detection of fluorescence from individual molecules.

Dual-curvilinear beam enabled tunable manipulation of high- and low-refractive-index particles

We present an innovative approach for the simultaneous agile manipulation of high-refractive-index (HRI) and low-refractive-index (LRI) particles. Our method involves introducing a dual-curvilinear optical vortex beam (DC-OVB) generated by superimposing a pair of curved beams: HRI and LRI particles are controlled by the bright curve and the dark channel between the two curves, respectively. The proposed DC-OVB provides customizable motion paths and velocities for both LRI and HRI particles. Each curve of the DC-OVB can support a distinct orbital flow density (OFD), enabling the application of torques to HRI and LRI particles, guiding them to orbit along specified trajectories and prompting them to execute various curvilinear motions simultaneously, including curvilinear movement, revolution, and rotation.

Ultra-robust informational metasurfaces based on spatial coherence structures engineering

Optical information transmission is vital in modern optics and photonics due to its concurrent and multi-dimensional nature, leading to tremendous applications such as optical microscopy, holography, and optical sensing. Conventional optical information transmission technologies suffer from bulky optical setup and information loss/crosstalk when meeting scatterers or obstacles in the light path. Here, we theoretically propose and experimentally realize the simultaneous manipulation of the coherence lengths and coherence structures of the light beams with the disordered metasurfaces. The ultra-robust optical information transmission and self-reconstruction can be realized by the generated partially coherent beam with modulated coherence structure even 93% of light is recklessly obstructed during light transmission, which brings new light to robust optical information transmission with a single metasurface. Our method provides a generic principle for the generalized coherence manipulation on the photonic platform and displays a variety of functionalities advancing capabilities in optical information transmission such as meta-holography and imaging in disordered and perturbative media.

Dynamic optimization of an integrated cultivation-aggregation model for mAb production.

Due to their proteinaceous structure, monoclonal antibodies (mAbs) are susceptible to irreversible aggregation, with harmful consequences on drug efficacy and patient safety. To mitigate this risk in modern biopharmaceutical processes, it is critical to comply with current good manufacturing practices (cGMP) and pursue operating strategies minimizing irreversible aggregation whilst also maximizing mAb throughput. These conflicting objectives are targeted in this study by formulating and analyzing an integrated dynamic model accounting for both cultivation and aggregation of mAbs from a Chinese Hamster Ovary (CHO) cell line. Two manipulated dynamic variables are considered here in simulation studies: firstly temperature manipulation within a batch reactor, and secondly feed flow manipulation within a series of isothermal fed-batch reactors. Following this, dynamic optimization investigations have been conducted, firstly with the single objective of maximizing mAb throughput and secondly with multiple (two) objectives of maximizing mAb throughput while also minimizing irreversible aggregate content, simultaneously. The study provides key insight into tradeoffs of how simultaneous temperature and feed flowrate manipulation affects mAb throughput and aggregation inside bioreactors.