Full-Combinatorial Concentration Gradient Array with 3D Micro/Nanofluidics for Antibiotic Susceptibility Testing.

Recent advancements in micro/nanofluidics have facilitated on-chip microscopy of cellular responses in a high-throughput and controlled microenvironment with the desired physicochemical properties. Despite its potential benefits to combination drug discovery, generating a complete combinatorial set of concentration gradients for multiple reagents in an array format remains challenging. The main reason is limited layouts of conventional micro/nanofluidic systems based on two-dimensional channel networks. In this paper, we present a device with three-dimensional (3D) interconnection of micro/nanochannels capable of generating a complete combinatorial set of concentration gradients for two reagents. The device was readily fabricated by laminating a pair of multilayered monolithic films containing a Christmas tree-like mixer, a cell culture chamber array, and through-holes, all within each single film. We assessed the reliable generation of a full-combinatorial concentration gradient array and validated it by using numerical analysis. We applied the proposed device to test the antibiotic susceptibility of bacterial cells in a convenient one-step manner. Furthermore, we explored the potential of the device to accommodate the arrayed complete combinatorial set for two or more drugs, while extending the capabilities of our laminated object manufacturing method for realizing 3D micro/nanofluidic systems.

In-Situ Gas Permeation-Driven Ionic Current Rectification of Heterogeneously Charged Nanopore Arrays.

Ionic diodes provide ionic current rectification (ICR), which is useful for micro-/nanofluidic devices for ionic current-mediated applications. However, the modulation of ICR is not fully developed, and current challenges include limited active control and localized modulation for further multiplexing of micro-/nanofluidic ionic diodes. Herein, a microfluidic device integrated with particle-assembly-based ionic diodes (PAIDs) and a gas-flow channel above them is presented. Exploiting in-situ gas permeation through a polymeric film, precise control over the physiochemical conditions of the nanopores within the PAIDs, leading to the modulation of ICR is demonstrated. The investigation not only characterizes the rectification properties of the PAIDs but also unveils their capacitor-like behavior and the ability to actively modulate ICR using various gas flows. Furthermore, the reversible modulation of ICR through dynamic switching of gas-dissolved solutions, enabling ion-signal amplification is showcased. This pioneering approach of in situ gas-permeation offers programmable manipulation of ion transport along PAIDs, thereby positioning ionic diodes as versatile nanofluidic components. Looking ahead, the development of multiplexed PAIDs in an addressable manner on a chip holds promise for practical applications across diverse fields, including ion signaling, ion-based logic, chemical reactors, and (bio)chemical sensing.

A Facile Strategy for the Fabrication of Cell-laden Porous Alginate Hydrogels Based on Two-phase Aqueous Emulsions.

Porous alginate hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden alginate hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of alginate and caseinate, are crosslinked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the caseinate phase from the ion-crosslinked alginate hydrogel. Those porous alginate hydrogels possess heterogeneous pores around 100 µm and interconnected paths. Human white adipose progenitors (WAPs) encapsulated in these hydrogels self-organize into spheroids and show enhanced viability, proliferation, and adipogenic differentiation, compared to non-porous constructs. As a proof of concept, this porous alginate hydrogel platform is employed to prepare core-shell spheres for coculture of WAPs and colon cancer cells, with WAP clusters distributed around cancer cell aggregates, to investigate cellular crosstalk. This efficacious approach is believed to provide a robust and versatile platform for engineering porous-structured alginate hydrogels for applications as cell carriers and in disease modeling.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

Synapse-Mimetic Hardware-Implemented Resistive Random-Access Memory for Artificial Neural Network.

Memristors mimic synaptic functions in advanced electronics and image sensors, thereby enabling brain-inspired neuromorphic computing to overcome the limitations of the von Neumann architecture. As computing operations based on von Neumann hardware rely on continuous memory transport between processing units and memory, fundamental limitations arise in terms of power consumption and integration density. In biological synapses, chemical stimulation induces information transfer from the pre- to the post-neuron. The memristor operates as resistive random-access memory (RRAM) and is incorporated into the hardware for neuromorphic computing. Hardware composed of synaptic memristor arrays is expected to lead to further breakthroughs owing to their biomimetic in-memory processing capabilities, low power consumption, and amenability to integration; these aspects satisfy the upcoming demands of artificial intelligence for higher computational loads. Among the tremendous efforts toward achieving human-brain-like electronics, layered 2D materials have demonstrated significant potential owing to their outstanding electronic and physical properties, facile integration with other materials, and low-power computing. This review discusses the memristive characteristics of various 2D materials (heterostructures, defect-engineered materials, and alloy materials) used in neuromorphic computing for image segregation or pattern recognition. Neuromorphic computing, the most powerful artificial networks for complicated image processing and recognition, represent a breakthrough in artificial intelligence owing to their enhanced performance and lower power consumption compared with von Neumann architectures. A hardware-implemented CNN with weight control based on synaptic memristor arrays is expected to be a promising candidate for future electronics in society, offering a solution based on non-von Neumann hardware. This emerging paradigm changes the computing algorithm using entirely hardware-connected edge computing and deep neural networks.

Artificial-Neural-Network-Driven Innovations in Time-Varying Process Diagnosis of Low-K Oxide Deposition.

To address the challenges in real-time process diagnosis within the semiconductor manufacturing industry, this paper presents a novel machine learning approach for analyzing the time-varying 10th harmonics during the deposition of low-k oxide (SiOF) on a 600 Å undoped silicate glass thin liner using a high-density plasma chemical vapor deposition system. The 10th harmonics, which are high-frequency components 10 times the fundamental frequency, are generated in the plasma sheath because of their nonlinear nature. An artificial neural network with a three-hidden-layer architecture was applied and optimized using k-fold cross-validation to analyze the harmonics generated in the plasma sheath during the deposition process. The model exhibited a binary cross-entropy loss of 0.1277 and achieved an accuracy of 0.9461. This approach enables the accurate prediction of process performance, resulting in significant cost reduction and enhancement of semiconductor manufacturing processes. This model has the potential to improve defect control and yield, thereby benefiting the semiconductor industry. Despite the limitations imposed by the limited dataset, the model demonstrated promising results, and further performance improvements are anticipated with the inclusion of additional data in future studies.

Diagnosing Time-Varying Harmonics in Low-k Oxide Thin Film (SiOF) Deposition by Using HDP CVD.

This study identified time-varying harmonic characteristics in a high-density plasma (HDP) chemical vapor deposition (CVD) chamber by depositing low-k oxide (SiOF). The characteristics of harmonics are caused by the nonlinear Lorentz force and the nonlinear nature of the sheath. In this study, a noninvasive directional coupler was used to collect harmonic power in the forward and reverse directions, which were low frequency (LF) and high bias radio frequency (RF). The intensity of the 2nd and 3rd harmonics responded to the LF power, pressure, and gas flow rate introduced for plasma generation. Meanwhile, the intensity of the 6th harmonic responded to the oxygen fraction in the transition step. The intensity of the 7th (forward) and 10th (in reverse) harmonic of the bias RF power depended on the underlying layers (silicon rich oxide (SRO) and undoped silicate glass (USG)) and the deposition of the SiOF layer. In particular, the 10th (reverse) harmonic of the bias RF power was identified using electrodynamics in a double capacitor model of the plasma sheath and the deposited dielectric material. The plasma-induced electronic charging effect on the deposited film resulted in the time-varying characteristic of the 10th harmonic (in reverse) of the bias RF power. The wafer-to-wafer consistency and stability of the time-varying characteristic were investigated. The findings of this study can be applied to in situ diagnosis of SiOF thin film deposition and optimization of the deposition process.

Physical Characteristics, Blue-Green Band Emission and Photocatalytic Activity of Au-Decorated ZnO Quantum Dots-Based Thick Films Prepared Using the Doctor Blade Technique.

Nanoscale ZnO is a vital semiconductor material whose versatility can be enhanced by sensitizing it with metals, especially noble metals, such as gold (Au). ZnO quantum dots were prepared via a simple co-precipitation technique using 2-methoxy ethanol as the solvent and KOH as the pH regulator for hydrolysis. The synthesized ZnO quantum dots were deposited onto glass slides using a simple doctor blade technique. Subsequently, the films were decorated with gold nanoparticles of different sizes using a drop-casting method. The resultant films were characterized via various strategies to obtain structural, optical, morphological, and particle size information. The X-ray diffraction (XRD) reveals the formation of the hexagonal crystal structure of ZnO. Upon Au nanoparticles loading, peaks due to gold are also observed. The optical properties study shows a slight change in the band gap due to Au loading. Nanoscale sizes of particles have been confirmed through electron microscope studies. P.L. studies display blue and blue-green band emissions. The significant degradation efficiency of 90.2% methylene blue (M.B.) was attained in natural pH in 120 min using pure ZnO catalyst while one drop gold-loaded catalysts, ZnO: Au 5 nm, ZnO: Au 7 nm, ZnO: Au 10 nm and ZnO: Au 15 nm, delivered M.B. degradation efficiency of 74.5% (in 245 min), 63.8% (240 min), 49.6% (240 min) and 34.0% (170 min) in natural pH, respectively. Such films can be helpful in conventional catalysis, photocatalysis, gas sensing, biosensing, and photoactive applications.

Randomized multicenter phase II trial of prophylactic irradiation of para-aortic lymph nodes in advanced cervical cancer according to tumor hypoxia: Korean Radiation Oncology Group (KROG 07-01) study.

We conducted a prospective phase II study on whether extended-field irradiation (EFI) confers survival benefits depending on hypoxic markers in locally advanced uterine cervical cancer (LAUCC). RNA-seq was performed to identify immune and hypoxic gene signatures. A total of 288 patients were randomized to either EFI or pelvic radiotherapy (PRT). All patients completed chemoradiotherapy. Overall, significantly higher 5-year para-aortic recurrence free survival (PARFS) rate occurred in EFI (97.6%) than in PRT group (87.2%), with marginal tendency to improve disease-free survival (DFS; 78% vs 70%, P = .066). Subgroup analyses were performed based on carbonic anhydrase 9 (CA9)-only positive, CA9/hypoxia-inducible factor (HIF) double positive and CA9 negative. In the CA9-only positive, EFI successfully increased 5-year PARFS (100% vs 76.4%, P = .010), resulting in significantly improved long-term DFS (85.7% vs 54.7%, P = .023) compared to the PRT, while there was no such benefit of EFI in the CA9/HIFs double positive. RNA-seq analysis identified distinct immunehigh subgroup with negative correlation with hypoxia gene signatures (R = -.37, P < .01), which showed a higher 5-year DFS than the immunelow (P = .032). Hypoxia-related genes were upregulated in the CA9/HIFs double positive compared to CA9 negative (P < .05). Only 17.4% of patients in CA9-negative group showed immunelow signatures, while 40.0% of patients in the double-positive group exhibited immunelow signatures. In conclusion, EFI improved PARFS significantly in all patients, but therapeutic efficacy of EFI in terms of improved DFS was solely observed in CA9-only positive LAUCC, and not in CA9/HIFs double-positive subgroup. RNA-seq analysis suggested that hypoxia-induced immunosuppression may be related to treatment resistance in LAUCC.

Chromism-Integrated Sensors and Devices for Visual Indicators.

The bifunctionality of chromism-integrated sensors and devices has been highlighted because of their reversibility, fast response, and visual indication. For example, one of the representative chromism electrochromic materials exhibits optical modulation under ion insertion/extraction by applying a potential. This operation mechanism can be integrated with various sensors (pressure, strain, biomolecules, gas, etc.) and devices (energy conversion/storage systems) as visual indicators for user-friendly operation. In this review, recent advances in the field of chromism-integrated systems for visual indicators are categorized for various chromism-integrated sensors and devices. This review can provide insights for researchers working on chromism, sensors, or devices. The integrated chromic devices are evaluated in terms of coloration-bleach operation, cycling stability, and coloration efficiency. In addition, the existing challenges and prospects for chromism-integrated sensors and devices are summarized for further research.

Combined Effects of Zeta-potential and Temperature of Nanopores on Diffusioosmotic Ion Transport.

Diffusioosmosis (DO) results from ion transport near charged surfaces in the presence of electrolyte gradients and is critical in nanofluidic systems. However, DO has not yet been comprehensively studied because nanofabrication materials have limitations of low throughput and difficult quantification. Herein, we describe a self-assembled particle membrane (SAPM)-integrated microfluidic platform that can modulate the material properties (e.g., zeta-potential) and transport flux of nanopores. We quantify the effect of the zeta-potential on DO by measuring the electrical signals across three different nanopores/nanochannels of the SAPM. We then empirically quantify the effects of the temperature and ionic strength of the electrolytes on DO and reveal a nonlinear relationship with DO-driven ion transport; the ionic strengths govern the DO- or diffusion-effective ion transport phenomena. Finally, we demonstrate DO-driven electric power generation with enhanced performance as a potential application under optimized experimental conditions.

High-Temperature Skin Softening Materials Overcoming the Trade-Off between Thermal Conductivity and Thermal Contact Resistance.

The trade-off between thermal conductivity (κ) and thermal contact resistance (Rc ) is regarded as a hurdle to develop superior interface materials for thermal management. Here a high-temperature skin softening material to overcome the trade-off relationship, realizing a record-high total thermal conductance (254.92 mW mm-2 K-1 ) for isotropic pad-type interface materials is introduced. A highly conductive hard core is constructed by incorporating Ag flakes and silver nanoparticle-decorated multiwalled carbon nanotubes in thermosetting epoxy (EP). The thin soft skin is composed of filler-embedded thermoplastic poly(ethylene-co-vinyl acetate) (PEVA). The κ (82.8 W m-1 K-1 ) of the PEVA-EP-PEVA interface material is only slightly compromised, compared with that (106.5 W m-1 K-1 ) of the EP core (386 µm). However, the elastic modulus (E = 2.10 GPa) at the skin is significantly smaller than the EP (26.28 GPa), enhancing conformality and decreasing Rc from 108.41 to 78.73 mm2 K W-1 . The thermoplastic skin is further softened at an elevated temperature (100 °C), dramatically decreasing E (0.19 GPa) and Rc (0.17 mm2 K W-1 ) with little change in κ, overcoming the trade-off relationship and enhancing the total thermal conductance by 2030%. The successful heat dissipation and applicability to the continuous manufacturing process demonstrate excellent feasibility as future thermal management materials.

Concurrent and Selective Determination of Dopamine and Serotonin with Flexible WS2 /Graphene/Polyimide Electrode Using Cold Plasma.

Makers of point-of-care devices and wearable diagnostics prefer flexible electrodes over conventional electrodes. In this study, a flexible electrode platform is introduced with a WS2 /graphene heterostructure on polyimide (WGP) for the concurrent and selective determination of dopamine and serotonin. The WGP is fabricated directly via plasma-enhanced chemical vapor deposition (PECVD) at 150 °C on a flexible polyimide substrate. Owing to the limitations of existing fabrication methods from physical transfer or hydrothermal methods, many studies are not conducted despite excellent graphene-based heterostructures. The PECVD synthesis method can provide an innovative WS2 /graphene heterostructure of uniform quality and sufficient size (4 in.). This unique heterostructure affords excellent electrical conductivity in graphene and numerous electrochemically active sites in WS2 . A large number of uniform qualities of WGP electrodes show reproducible and highly sensitive electrochemical results. The synergistic effect enabled well-separated voltammetric signals for dopamine and serotonin with a potential gap of 188 mV. Moreover, the practical application of the flexible sensor is successfully evaluated by using artificial cerebrospinal fluid.

Compensatory Mutations in GI and ZTL May Modulate Temperature Compensation in the Circadian Clock.

Circadian systems share the three properties of entrainment, free-running period, and temperature compensation (TC). TC ensures nearly the same period over a broad range of physiologically relevant temperatures; however, the mechanisms behind TC remain poorly understood. Here, we identify single point mutations in two key elements of the Arabidopsis circadian clock, GIGANTEA (GI) and ZEITLUPE (ZTL), which likely act as compensatory substitutions to establish a remarkably constant free-running period over a wide range of temperatures. Using near-isogenic lines generated from the introgression of the Cape Verde Islands (Cvi) alleles of GI and ZTL into the Landsberg erecta (Ler) background, we show how longer periods in the Cvi background at higher temperatures correlate with a difference in strength of the GI/ZTL interaction. Pairwise interaction testing of all GI/ZTL allelic combinations shows similar affinities for isogenic alleles at 22°C, but very poor interaction between GI (Cvi) and ZTL (Cvi) at higher temperature. In vivo, this would result in lower ZTL levels at high temperatures leading to longer periods in the Cvi background. Mismatched allelic combinations result in extremely strong or weak GI/ZTL interactions, indicating how the corresponding natural variants likely became fixed through epistatic selection. Additionally, molecular characterization of GI (Cvi) reveals a novel functional motif that can modulate the GI/ZTL interaction as well as nucleocytoplasmic partitioning. Taken together, these results identify a plausible temperature-dependent molecular mechanism, which contributes to the robustness of TC through natural variation in GI and ZTL alleles found on the Cape Verde Islands.

Ribosomal protein S3 is a novel negative regulator of non-homologous end joining repair of DNA double-strand breaks.

DNA double-strand breaks (DSBs) are one of the most serious types of DNA damage. However, multiple repair pathways are present in cells to ensure rapid and appropriate repair of DSBs. Pathway selection depends on several factors including cell type, cell cycle phase, and damage severity. Ribosomal protein S3 (rpS3), a component of the 40S small ribosomal subunit, is a multi-functional protein primarily involved in protein synthesis. rpS3 is also involved in the mediation of various extra-ribosomal pathways, including DNA damage processing and the stress response. Here, we report that rpS3 is a novel negative regulator of non-homologous end joining (NHEJ)-mediated repair of DSBs. We found that rpS3 interacts with the Ku heterodimers of the DNA-dependent protein kinase (DNA-PK) complex and slows down NHEJ ligation reactions, ultimately triggering p53-dependent cell death following treatment with high-dose ionizing radiation. After DSB formation, DNA-PK phosphorylates rpS3, which consequently reduces the binding of rpS3 to the Ku complex. We hypothesized that rpS3 may play a role in DSB repair by repressing NHEJ, while inducing other repair pathways, and by initiating DSB-induced cell death in response to severe DNA damage.

Recyclable free-polymer transfer of nano-grain MoS2 film onto arbitrary substrates.

Clean transfer of transition metal dichalcogenides (TMDs) film is highly desirable, as intrinsic properties of TMDs may be degraded in a conventional wet transfer process using a polymer-based resist and toxic chemical solvent. Residues from the resists often remain on the transferred TMDs, thereby causing a significant variation in their electrical and optical characteristics. Therefore, an alternative to the conventional wet transfer method is needed-one in which no residue is left behind. Herein, we report that our molybdenum disulfide (MoS2) films synthesized by plasma-enhanced chemical vapor deposition can be easily transferred onto arbitrary substrates (such as SiO2/Si, polyimide, fluorine-doped tin oxide, and polyethersulfone) by using water alone, i.e. without residues or chemical solvents. The transferred MoS2 film retains its original morphology and physical properties, which are investigated by optical microscopy, atomic force microscopy, Raman, x-ray photoelectron spectroscopy, and surface tension analysis. Furthermore, we demonstrate multiple recycling of the resist-free transfer for the nano-grain MoS2 film. Using the proposed water-assisted and recyclable transfer, MoS2/p-doped Si wafer photodiode was fabricated, and the opto-electric properties of the photodiode were characterized to demonstrate the feasibility of the proposed method.

Synthesis of vertically aligned wafer-scale tantalum disulfide using high-Ar/H2S ratio plasma.

Nanostructural modification of two-dimensional (2D) materials has attracted significant attention for enhancing hydrogen evolution reaction (HER) activity. In this study, the nanostructure of TaS2films was controlled by controlling the Ar/H2S gas ratio used in plasma-enhanced chemical vapor deposition (PECVD). At a high Ar/H2S gas ratio, vertically aligned TaS2(V-TaS2) films were formed over a large-area (4 in) at a temperature of 250 °C, which, to the best of our knowledge, is the lowest temperature reported for PECVD. Furthermore, the plasma species formed in the injected gas at various Ar/H2S gas ratios were analyzed using optical emission spectroscopy to determine the synthesis mechanism. In addition, the 4 in wafer-scale V-TaS2was analyzed by x-ray photoelectron spectroscopy, transmission electron microscopy, and atomic force microscopy, and the HER performance of the as-synthesized TaS2fabricated with various Ar/H2S ratios was measured. The results revealed that, depending on the film structure of TaS2, the HER performance can be enhanced owing to its structural advantage. Furthermore, the excellent stability and robustness of V-TaS2was confirmed by conducting 1000 HER cycles and post-HER material characterization. This study provides important insights into the plasma-assisted nanostructural modification of 2D materials for application as enhanced electrocatalysts.

Prediction of hand-wrist maturation stages based on cervical vertebrae images using artificial intelligence.

OBJECTIVE: To predict the hand-wrist maturation stages based on the cervical vertebrae (CV) images, and to analyse the accuracy of the proposed algorithms. SETTINGS AND POPULATION: A total of 499 pairs of hand-wrist radiographs and lateral cephalograms of 455 orthodontic patients aged 6-18 years were used for developing the prediction model for hand-wrist skeletal maturation stages. MATERIALS AND METHODS: The hand-wrist radiographs and the lateral cephalograms were collected from two university hospitals and a paediatric dental clinic. After identifying the 13 anatomic landmarks of the CV, the width-height ratio, width-perpendicular height ratio and concavity ratio of the CV were used as the morphometric features of the CV. Patients' chronological age and sex were also included as input data. The ground truth data were the Fishman SMI based on the hand-wrist radiographs. Three specialists determined the ground truth SMI. An ensemble machine learning methods were used to predict the Fishman SMI. Five-fold cross-validation was performed. The mean absolute error (MAE), round MAE and root mean square error (RMSE) values were used to assess the performance of the final ensemble model. RESULTS: The final ensemble model consisted of eight machine learning models. The MAE, round MAE and RMSE were 0.90, 0.87 and 1.20, respectively. CONCLUSION: Prediction of hand-wrist SMI based on CV images is possible using machine learning methods. Chronological age and sex increased the prediction accuracy. An automated diagnosis of the skeletal maturation may aid as a decision-supporting tool for evaluating the optimal treatment timing for growing patients.

Development of Force Sensor System Based on Tri-Axial Fiber Bragg Grating with Flexure Structure.

Fiber Bragg grating (FBG) sensors have an advantage over optical sensors in that they are lightweight, easy to terminate, and have a high flexibility and a low cost. Additionally, FBG is highly sensitive to strain and temperature, which is why it has been used in FBG force sensor systems for cardiac catheterization. When manually inserting the catheter, the physician should sense the force at the catheter tip under the limitation of power (<0.5 N). The FBG force sensor can be optimal for a catheter as it can be small, low-cost, easy to manufacture, free of electromagnetic interference, and is materially biocompatible with humans. In this study, FBG fibers mounted on two different flexure structures were designed and simulated using ANSYS simulation software to verify their sensitivity and durability for use in a catheter tip. The selected flexure was combined with three FBGs and an interrogator to obtain the wavelength signals. To obtain a calibration curve, the FBG sensor obtained data on the change in wavelength with force at a high resolution of 0.01 N within the 0.1-0.5 N range. The calibration curve was used in the force sensor system by the LabVIEW program to measure the unknown force values in real time.

Double-Sided Microwells with a Stepped Through-Hole Membrane for High-Throughput Microbial Assays.

To improve the throughput of microwell arrays for identifying immense cellular diversities even at a single-bacteria level, further miniaturization or densification of the microwells has been an obvious breakthrough. However, controlling millions of nanoliter samples or more at the microscale remains technologically difficult and has been spatially restricted to a single open side of the microwells. Here we employed a stepped through-hole membrane to utilize the bottom as well as top side of a high-density nanoliter microwell array, thus improving spatial efficiency. The stepped structure shows additional effectiveness for handling several millions of nanoliter bacterial samples in the overall perspectives of controllability, throughput, simplicity, versatility, and automation by using novel methods for three representative procedures in bacterial assays: partitioning cells, manipulating the chemical environment, and extracting selected cells. As a potential application, we show proof-of-concept isolation of rare cells in a mixed ratio of 1 to around 106 using a single chip. Our device can be further applied to various biological studies pertaining to synthetic biology, drug screening, mutagenesis, and single-cell heterogeneity.