Modular Platform Research Articles

Development of a Modular Virtual Calibration Platform for Power Machinery

The hardware-in-the-loop (HIL)-based virtual calibration technology for power machinery significantly enhances the efficiency and flexibility of electronic controller calibration, reducing dependency on physical experiments and lowering development costs. This paper presents an independently developed modular virtual calibration platform, designed based on the ISO/IEC 42010 architecture approach and the V-Model development process. The platform adopts a modular layered architecture comprising the physical layer, communication layer, model layer, software layer, and application layer. Each layer is independently developed and seamlessly integrated, ensuring excellent scalability and maintainability. Through performance validation conducted under steady-state and transient operating conditions of the diesel/natural gas dual-fuel engine electronic control unit (ECU), experimental results demonstrated that the platform possesses high computational accuracy, rapid response capability, and stable operation across different scenarios. The experiments validated that the platform can effectively replicate the real behavior of the controlled units in a virtual environment, confirming its adaptability and reliability. The platform offers an efficient and reliable solution for power machinery controller calibration.

Secondary Alkylation of Arenes via the Borono-Catellani Strategy.

A modular platform technology for the synthesis of α-aryl carbonyl derivatives via Borono-Catellani-type secondary alkylation of arenes is presented. This practical method features a broad substrate scope regarding aryl boronic acid catechol esters, secondary alkyl bromides, and diversified terminating reagents (e.g., olefins, alkynes, and Zn(CN)2), mild reaction conditions, and good functional-group tolerance. Importantly, the asymmetric version based on a dynamic kinetic asymmetric transformation (DyKAT) has also been realized by introducing the 1:1 diastereomeric mixture of α-bromo carboxamides bearing an Evans chiral auxiliary as the electrophiles, and constantly excellent diastereoselectivities (>20:1 d.r.) are obtained. Notably, the obtained chiral products can be readily transformed into diversified enantioenriched α-aryl propionic acid derivatives, laying a solid foundation for the discovery of new NSAIDs. Through mechanistic studies and DFT calculations, a critical stereoretentive oxidative addition step is revealed in this Borono-Catellani secondary alkylation reaction, and the origins of stereodiscrimination of this DyKAT are well explained.

Catalytic Asymmetric 1,4-Hydrocarbonation of 1,3-Enynes via Photoredox/Cobalt/Chromium Triple Catalysis.

A synergistic photoredox/cobalt/chromium triple catalysis system for regioselective, enantioselective, and diastereoselective 1,4-hydrocarbonation of readily available 1,3-enyne precursors was explored, providing a modular synthetic platform for various trisubstituted axially chiral allenes bearing an extra central chirality. The protocol features a broad substrate scope, good functional group tolerance, excellent selectivity, and mild reaction conditions. Furthermore, a possible reaction mechanism is proposed based on numerous control experiments and density functional theory calculations.

Genetically Programmed Single-Component Protein Hydrogel for Spinal Cord Injury Repair.

Protein self-assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single-component self-assembling hydrogel is developed using the recombinant protein CsgA, and its successful application for spinal cord injury repair is demonstrated. Gelation is achieved by the physical entanglement of CsgA nanofibrils, resulting in a self-supporting hydrogel at low concentrations (≥5mg mL-1). By leveraging the programmability of the CsgA gene sequence, the bioactive hydrogel is enhanced by fusing functional peptide GHK. GHK is recognized for its anti-inflammatory, antioxidant, and neurotrophic factor-stimulating properties, making it a valuable addition to the hydrogel for spinal cord injury repair applications. In vitro experiments demonstrate that the CsgA-GHK hydrogel can modulate microglial M2 polarization, promote neuronal differentiation of neural stem cells, and inhibit astrocyte differentiation. Additionally, the hydrogel shows efficacy in alleviating inflammation and promotes neuronal regeneration at the injury site, leading to significant functional recovery in a rat model with compression injury spinal cord cavity. These findings lay the groundwork for developing a modular design platform for recombinant CsgA protein hydrogels in tissue repair applications.

Photo-rechargeable zinc ion capacitors using MoS2/NaTaO3/CF dual-acting electrodes prepared by photodeposition method.

This study presents an innovative approach to integrated energy systems by combining solar energy harvesting and electrochemical charge storage in a single modular platform. By strategically incorporating a MoS2/NaTaO3 heterostructure material, we have developed a photo-rechargeable zinc-ion capacitor (PR-ZIC) that utilises the synergistic benefits of this unique configuration. The photoactive MoS2/NaTaO3 cathode effectively absorbs light and charges the capacitor, enabling continuous light-driven operation. Experimental studies show that the MoS2/NaTaO3-based photo-rechargeable zinc-ion capacitor (PR-ZIC) exhibits a significant increase in capacitance when irradiated with light, with a 2.76-fold increase (93.94 mF cm-2) compared to dark conditions (33.95 mF cm-2) at a 10 mV s-1 scan rate. In addition, these capacitors show a photocharge voltage response of about 860 mV and excellent cyclability, retaining about 96% of their capacity over 4000 charge-discharge cycles. The results of this study highlight the potential of the MoS2/NaTaO3 heterostructure as a high-performance photoactive material for advanced photo-rechargeable zinc-ion energy storage devices. This integrated approach offers innovative off-grid energy solutions by optimizing device footprint, minimizing energy transfer losses and providing sustainable energy storage options.

Innovative Approaches to the Development and Application of Software in International and Warehouse Logistics: Current Trends and Future Perspectives

Abstract This study aims to explore the transformative role of advanced logistics software in optimizing supply chain operations. It highlights how cutting-edge technologies such as AI, IoT, and blockchain are integrated to enhance operational efficiency, reduce costs, and improve service delivery. Methodology - The research applies a mixed-method approach, combining quantitative analysis of logistics performance metrics with qualitative case studies of companies that have implemented advanced logistics software. Data were collected from industry reports and academic literature to assess the impact of these technologies. Findings - The analysis revealed that integrating advanced logistics technologies can reduce operational costs by 15-20% and improve delivery times by 25%, as evidenced by ARDI Express. Moreover, the adoption of modular software platforms enables firms to customize solutions based on their specific needs, ensuring flexibility and scalability. Companies like Amazon and Walmart have achieved significant improvements in route optimization and demand forecasting through AI-powered systems. Conclusion - The study concludes that advanced logistics software is crucial for maintaining competitiveness in a dynamic market. Future research should focus on developing unified platforms tailored for small and medium enterprises (SMEs) and exploring the potential of AI in autonomous logistics systems.

Pooled Nanoparticle Screening Using a Chemical Barcoding Approach.

We report the development of a small molecule-based barcoding platform for pooled screening of nanoparticle delivery. Using aryl halide-based tags (halocodes), we achieve high-sensitivity detection via gas chromatography coupled with mass spectrometry or electron capture. This enables barcoding and tracking of nanoparticles with minimal halocode concentrations and without altering their physicochemical properties. To demonstrate the utility of our platform for pooled screening, we synthesized a halocoded library of polylactide-co-glycolide (PLGA) nanoparticles and quantified uptake in ovarian cancer cells in a pooled manner. Our findings correlate with conventional fluorescence-based assays. Additionally, we demonstrate the potential of halocodes for spatial mapping of nanoparticles using mass spectrometry imaging (MSI). Halocoding presents an accessible and modular nanoparticle screening platform capable of quantifying delivery of pooled nanocarrier libraries in a range of biological settings.

Modular self-emulsifying drug delivery platform to enhance cellular uptake activity in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) presents with resistance phenotypes to certain therapies, such as cisplatin, often requiring higher dosing, with associated acquired tumor resistance, renal toxicity, and variable patient responses. A self-emulsifying drug delivery (SEDD) formulation approach was proposed to overcome the limitations of cisplatin in TNBC, focusing on improving intracellular cisplatin and control siRNA uptake as a proof-of-principle of dual drug delivery. Four SEDD formulations were prepared and optimized for cisplatin (o/w) emulsion and FITC-siRNA (w/o) emulsion using pseudo-ternary phase diagrams to facilitate the formation of water-in-oil-water (w/o/w) emulsions. Formulations were characterized by size, polydispersity (PDI), and surface charge and tested in vitro. Cellular uptake via triplex staining of drug-loaded SEDDs was investigated. SEDDs showed enhanced internalization and promoted selective TNBC cellular uptake. The current study is a proof-of-principle for the successful co-delivery of cisplatin (small molecule) and siRNA (large molecule) via the SEDDs platform.

Utilizing Alkyne-Nitrone Cycloaddition for the Convenient Multi-Component Assembly of Protein Degraders and Biological Probes.

Proteolysis-targeting chimeras (PROTACs) have become a popular therapeutic strategy, and the development of multi-functional PROTACs has added complexity to their synthetic process. Although click reactions have been widely applied to prepare highly functionalized biomolecules, most of them are limited to two-component reactions, restricting the creation of more complex structures. Here, we developed a convenient multi-component assembly strategy via strain-promoted alkyne-nitrone cycloaddition (SPANC), which can be extended to a 3-component reaction when combined with nitrone formation. Using the 2-component assembly, we demonstrated the targeted protein degradation with both preassembled and in-cell assembled PROTACs. This strategy was also applied to facilitate the screening of E3 ligases in PROTACs and the preparation of various biological probes. Moreover, the 3-component assembly, via sequential nitrone formation and SPANC, enabled the synthesis of trifunctional 3-component PROTACs. The N-substituent, serving as an additional functional moiety, was designed as a photocage for sterically controlling PROTAC activity. The 3-component assembly can be further modified to provide additional control or enhance the cell-targeting ability of PROTACs. In short, our multi-component SPANC assembly strategy offers a modular and versatile synthetic platform for creating multi-functional PROTACs and biological probes.

Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review.

Modular (universal) CAR T-platforms were developed to combat the limitations of traditional CAR-T therapy, allowing for multiple targeting of tumor-associated antigens and the ability to control CAR-T cell activity. The modular CAR-T platform consists of a universal receptor (signaling module) that recognizes an adapter molecule on the soluble module, which is responsible for antigen recognition. Multiple platforms have been developed over the last 12 years, and some of them have entered the clinical trial phase. This systematic review seeks to evaluate the different parameters of modular CAR-T platforms performance in animal models. A systematic search of literature in the PubMed database and in Google Scholar and BASE (Bielefeld Academic Search Engine) search engines was performed according to predefined eligibility criteria. All studies conducted on xenograft mouse models with any variant of modular CAR-T platforms were included. Forest plots were generated for visual presentation of the extracted quantitative findings (standardized mean difference (SMD) and median survival rate (MSR)). A total of 33 studies employing 15 different modular CAR-T platforms were included. The platforms varied in terms of CAR-T cells, soluble module doses, and their frequency of administration. The studies showed a reduction in tumor burden and in tumor volume compared to the combined negative group. In comparison with the positive control group, there was no significant change in tumor burden or volume. In all the included studies the experimental group had a higher survival probability compared to the combined negative group at the study endpoint, with no significant difference in survival rate compared to the positive control group. The modular CAR-T platforms are generally effective and are a valuable addition to the arsenal of CAR therapy. https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023443984.

Selective Gas Adsorption in Permanently Microporous Coordination Cages with Exposed Metal Sites.

Porous coordination cages (PCCs), molecular analogs of metal-organic frameworks, offer modular platforms for studying the adsorption properties of small molecules, with coordinatively unsaturated metal centers playing a pivotal role in tuning these behaviors. In this work, we present the synthesis, activation, and detailed gas adsorption studies of second-row transition metal-based M24L24 cuboctahedral cages, specifically Mo24(bdc)24, Rh24(bdc)24, and [Ru24(bdc)24]Cl12. These materials represent rare examples of Mo-, Rh-, and Ru-based hybrid porous solids. The synthesis and activation of these cages were optimized to maximize porosity, yielding BET surface areas of up to 832 m2/g. Gas adsorption studies with CO2 and CO reveal distinctive uptake behaviors linked to the metal cations, with Mo24(bdc)24 demonstrating the highest gravimetric CO2 uptake (2.12 mmol/g at 298 K) and [Ru24(bdc)24]Cl12 exhibiting the strongest CO binding (-75 kJ/mol). Additionally, we explore the selective adsorption of unsaturated hydrocarbons, such as ethylene and propylene, revealing strong binding interactions at low pressures as a result of strong metal-hydrocarbon interactions based on pi-backbonding interactions.

Automation of multiplex biochemical assays to enhance productivity and reduce cycle time using a modular robotic platform

Pharmaceutical and biotechnology companies are increasingly being challenged to shorten the cycle time between design, make, test, and analyze (DMTA) compounds. Automation of multiplex assays to obtain multiparameter data on the same robotic run is instrumental in reducing cycle time. Consequently, an increasing need in automated systems to streamline laboratory workflows with the goal to expedite assay cycle time and enhance productivity has grown in industrial and academic institutions in the past decades. Herein, we present a customized robotic platform with operational modularity and flexibility, designed to automate entire assay workflows involving multistep reagent dispensing, mixing, lidding/de-lidding, incubation, centrifugation, and final readout steps by linking spinnaker robot with various peripheral instruments. Compared to manual workflows, the system can seamlessly execute processes with high efficiency, evaluated by standard assay validation protocols for robustness and reproducibility. Furthermore, the system can perform multiple, independent protocols in parallel, and has high-throughput capacity. In this publication, we demonstrate that the modular robotic platform can fully automate multiplex assay workflows through ‘one-click-and-run’ solution with tremendous benefits in liberating manual intervention, boosting productivity while producing high-quality data combined with reduced cycle time (>20%), as well as expanding the capacity for higher throughput.

Compact modular open platform for low-cost ultrasound imaging: Ralisation and measurements in biological settings

Compact modular open platform for low-cost ultrasound imaging: Ralisation and measurements in biological settings

The Implementation of a New Modular Robotic Platform in Anatomical Lung Resections with a Triportal robotic-Assisted Technique: Technical Issues

The Implementation of a New Modular Robotic Platform in Anatomical Lung Resections with a Triportal robotic-Assisted Technique: Technical Issues

A modular platform for nucleic acid-driven multimerization of nanobodies for advanced molecular imaging

A modular platform for nucleic acid-driven multimerization of nanobodies for advanced molecular imaging

Post-Transcriptional Modular Synthetic Receptors.

Inspired by the power of transcriptional synthetic receptors and hoping to complement them to expand the toolbox for cell engineering, we establish LIDAR (Ligand-Induced Dimerization Activating RNA editing), a modular post-transcriptional synthetic receptor platform that harnesses RNA editing by ADAR. LIDAR is compatible with various receptor architectures in different cellular contexts, and enables the sensing of diverse ligands and the production of functional outputs. Furthermore, LIDAR can sense orthogonal signals in the same cell and produce synthetic spatial patterns, potentially enabling the programming of complex multicellular behaviors. Finally, LIDAR is compatible with compact encoding and can be delivered as synthetic mRNA. Thus, LIDAR expands the family of synthetic receptors, holding the promise to empower basic research and therapeutic applications.

Autonomous and Closed-Loop Exploration and Optimization of Bioelectrocatalytic Systems

Automated electrochemistry platforms provide a pathway for speeding up the discovery and optimization of electrochemical systems, especially when a broad range of molecules and reaction conditions must be explored.1-3 Additionally, incorporation of machine learning enables closed-loop optimization campaigns, where the obtained experimental data guides the selection of the next set of experimental parameters to test. This type of autonomous exploration is ideally suited for the study of enzyme electrocatalysis, as the combinatorics of different enzymes, substrates, and redox mediators creates a prohibitively large parameter space. Even within a single enzyme class, mutations to the amino acid sequence can significantly impact rate, function, and selectivity of the catalyzed reaction. Thus, an automated electrochemical platform that enables rapid sampling both reaction parameters and amino acid sequence space would enable discovery of new, non-native enzymatic reactions.In this work we use an open source and modular automated electrochemistry platform to study enzyme electrocatalysis in several common bioelectrocatalytic systems, such as glucose oxidase, glucose dehydrogenase, and aldehyde dehydrogenase. We use automated cyclic voltammetric substrate titration experiments (Figure 1) to gain insight into the kinetics of the redox-mediated enzymatic catalysis and demonstrate the reaction conditions in which traditional mechanistic simplifications, like Michaelis-Menten, break down. Additionally, the automated electrochemistry platform allows for the rapid screening of different substrate molecules, enabling the quantification of substrate promiscuity in these enzymatic catalysts. We show how Bayesian Optimization can be incorporated into our workflow to autonomously tune solution parameters to promote increased reaction rates. These studies demonstrate the power of autonomous electrochemistry for understanding and screening biocatalytic systems and represent a significant step towards totally machine-guided biocatalyst evolution.[1] Oh, I. ; Pence, M. A.; Lukhanin, N.; Rodriguez, O.; Schroeder, C. M.*; Rodriguez-Lopez, J.*, “The Electrolab: An open-source, modular platform for automated characterization of redox-active electrolytes” Device, 2023, 1, 5, 100103[2] Rodriguez, O.; Pence, M. A.; Rodriguez-Lopez, J.*, “Hard Potato: An Open Source Python Library to Control Commercially Available Potentiostats and Automate Electrochemical Experiments” Anal. Chem., 2023, 95, 4840–4845[3]Pence, M. A.; Rodriguez, O.; Lukhanin, N.; Schroeder, C. M.*; Rodriguez-Lopez, J.*, “Automated Measurement of Electrogenerated Redox Species Degradation Using Multiplexed Interdigitated Electrode Arrays”, ACS Meas. Sci. Au, 2023, 3, 62–72 Figure 1

Modular Synthetic Platform to Tailor Therapeutic-Specific Delivery in Injectable Hydrogels.

Injectable thermoresponsive hydrogels (thermogels), valued for their conformability and minimal invasiveness, are increasingly used as in situ forming implants for drug delivery and as regenerative scaffolds. These gels exhibit sol-to-gel phase transitions at body temperature. As localized depots and scaffolds, these gels determine the chemical and mechanical environments and could dramatically influence the release kinetics of drugs or the fate of cells. Current synthetic approaches for thermogels, however, often limit the ability to fully exploit interactions between the thermogel matrix and the encapsulated agent. In this study, we introduce a modular synthetic platform for creating a library of functionalized polyurethane thermogels that enables customization of gelation properties and intermolecular interactions. These thermogels can exhibit a wide range of stiffness, offer complementary ionic interactions, and enhance hydrophobic interactions and hydrogen bonding. By leveraging these tunable interactions between the thermogelling scaffold, functional groups, and encapsulated agents, we achieved sustained and controlled release, from days to over 6 months, for both low and high molecular weight drug analogs. Release profiles varied from monophasic to biphasic and triphasic depending on the compatibility between the thermogel properties and the encapsulated agents. The design rules identified here support the development of drug-specific formulations, facilitating precise, sustained, and modulated release tailored to therapeutic needs. Beyond providing an adaptable strategy for customizable injectable drug depots, this synthetic strategy lays the groundwork for future iterations of multi stimuli-responsive thermogels with enhanced bioactivity, advancing the potential for customizable, biointeractive therapeutic systems.

A modular platform for bioluminescent RNA tracking

A complete understanding of RNA biology requires methods for tracking transcripts in vivo. Common strategies rely on fluorogenic probes that are limited in sensitivity, dynamic range, and depth of interrogation, owing to their need for excitation light and tissue autofluorescence. To overcome these challenges, we report a bioluminescent platform for serial imaging of RNAs. The RNA tags are engineered to recruit light-emitting luciferase fragments (termed RNA lanterns) upon transcription. Robust photon production is observed for RNA targets both in cells and in live animals. Importantly, only a single copy of the tag is necessary for sensitive detection, in sharp contrast to fluorescent platforms requiring multiple repeats. Overall, this work provides a foundational platform for visualizing RNA dynamics from the micro to the macro scale.

Photoredox-Catalyzed Multicomponent α-Sulfonylation of Terminal Alkynes.

A generality-oriented and adaptive α-sulfonylation of alkynes via photoinduced multicomponent radical cross-coupling of terminal alkynes with sulfinates and a variety of alcohols, thiophenols, or selenophenols has been explored. This protocol features mild conditions, good functional group tolerability, broad substrate scope, excellent chemo-, site-, and stereoselectivity, and applicability to late-stage functionalization. It provides a modular platform for the synthesis of value-added structurally diverse α-sulfonyl-containing multisubstituted alkenes from simple precursors.