Search Results (22)

This paper presents a theoretical and experimental investigation of the amplitude–frequency response of a triple-microcantilever system designed for real-time ultra-low mass detection. The present study focuses on the unfunctionalized configuration to clarify the intrinsic electromechanical behavior of this system. Starting with analytical expressions, output voltage amplitude–frequency responses are derived for a Wheatstone-bridge-based readout circuit and used to analyze the relationship between the resonant frequencies and mechanical amplitude–frequency responses of the three microcantilevers and the resulting electrical response. The extrema and zero-crossing points of the output voltage do not trivially coincide with the individual resonance peaks or their intersection points; this offers more freedom for defining strong detection criteria. A specialized experimental setup has been developed and used to measure the frequency response of a fabricated triple-microcantilever prototype; good agreement with the theoretical predictions has been found within the operating range. Initial humidification tests confirm the high sensitivity of the microsystem against small added masses, corresponding to an estimated detection limit on the order of 10⁻¹⁶ kg for the unfunctionalized device. In this way, the present work confirms the validity of the proposed triple-microcantilever configuration for ultra-low mass sensing and outlines its potential for future application in pathogen detection upon surface functionalization. Full article

A lateral overflow integration capacitor (LOFIC) CMOS image sensor (CIS) can achieve high-dynamic-range (HDR) imaging by combining a low-conversion-gain (LCG) signal with a high-conversion-gain (HCG) signal. However, the signal-to-noise ratio (SNR) drops at the switching point from HCG signal to LCG signal due to the significant pixel noise in the LCG signal. To address this issue, a triple-gain LOFIC CIS with a middle-conversion-gain (MCG) signal has been introduced. In this work, we propose an area-efficient readout circuit for the triple-gain LOFIC CIS, using amplifier and capacitor sharing techniques to process the HCG, MCG, and LCG signals. A test chip of the proposed readout circuit was fabricated using the $0.18\mathsf{\mu }$m CMOS process. The area overhead was only $7.6\%$, and the SNR drop was improved by $8.05$ dB compared to the readout circuit for a dual-gain LOFIC CIS. Full article

Cancer metabolic reprogramming plays a critical role in tumor progression and therapeutic resistance, underscoring the need for advanced analytical strategies. Metabolomics, leveraging mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, offers a comprehensive and functional readout of tumor biochemistry. By enabling both targeted metabolite quantification and untargeted profiling, metabolomics captures the dynamic metabolic alterations associated with cancer. The integration of metabolomics with machine learning (ML) approaches further enhances the interpretation of these complex, high-dimensional datasets, providing powerful insights into cancer biology from biomarker discovery to therapeutic targeting. This review systematically examines the transformative role of ML in cancer metabolomics. We discuss how various ML methodologies—including supervised algorithms (e.g., Support Vector Machine, Random Forest), unsupervised techniques (e.g., Principal Component Analysis, t-SNE), and deep learning frameworks—are advancing cancer research. Specifically, we highlight three major applications of ML–metabolomics integration: (1) cancer subtyping, exemplified by the use of Similarity Network Fusion (SNF) and LASSO regression to classify triple-negative breast cancer into subtypes with distinct survival outcomes; (2) biomarker discovery, where Random Forest and Partial Least Squares Discriminant Analysis (PLS-DA) models have achieved >90% accuracy in detecting breast and colorectal cancers through biofluid metabolomics; and (3) prognostic modeling, demonstrated by the identification of race-specific metabolic signatures in breast cancer and the prediction of clinical outcomes in lung and ovarian cancers. Beyond these areas, we explore applications across prostate, thyroid, and pancreatic cancers, where ML-driven metabolomics is contributing to earlier detection, improved risk stratification, and personalized treatment planning. We also address critical challenges, including issues of data quality (e.g., batch effects, missing values), model interpretability, and barriers to clinical translation. Emerging solutions, such as explainable artificial intelligence (XAI) approaches and standardized multi-omics integration pipelines, are discussed as pathways to overcome these hurdles. By synthesizing recent advances, this review illustrates how ML-enhanced metabolomics bridges the gap between fundamental cancer metabolism research and clinical application, offering new avenues for precision oncology through improved diagnosis, prognosis, and tailored therapeutic strategies. Full article

A comprehensive multi-jet physics program is anticipated for experiments at future colliders. Key physics processes necessitate detectors that can distinguish signals from W and Z bosons and the Higgs boson. Typical examples include channels with $W^{+}{W}^{-}$ or $Z^o{Z}^o$ pairs and processes involving new physics in those cases where neutral particles must be disentangled from charged ones due to the presence of W or Z bosons in their final states. Such a physics program demands calorimetric energy resolution at or beyond the limits of traditional calorimetric techniques. Multiple-readout calorimetry, which aims to reduce fluctuations in energy measurements of hadronic showers, is a promising approach. The first part of this article reviews dual- and triple-readout calorimetry within a mathematical framework describing the underlying compensating mechanism. The second part proposes a potential implementation using an integrally active and total absorption detector. This model serves as the basis for several Monte Carlo studies, illustrating how the response of a multiple-readout calorimeter depends on construction parameters. Among the layouts considered, one configuration operating in triple-readout mode shows the potential to achieve an energy resolution approaching $20\%/\sqrt{E}$. Full article

A new off-axis optical design alternative to that of the GRACE Follow-on mission for future NGGM missions is considered. In place of the triple-mirror assembly of the GRACE Follow-on mission, a laser retro-reflector is instead generated by means of lens systems. The receiving (RX) beam and transmitting (TX) beam are enforced to be anti-parallel by a control loop with differential wavefront sensing (DWS) signals as readout, and a fast-steering mirror is employed to actuate the pointing of the local beam. The tilt-to-length (TTL) coupling noise of the new off-axis optical bench layout is carefully studied in the present work. Local TTL originated from piston noise as well as assembly and alignment errors of optical components are studied. Effort is also made to have an in depth understanding of global TTL due to relative attitude jitter between spacecraft. The margin of TTL noise in the position noise budget for laser ranging is examined. With an open loop control of the offset between the reference point of the optical bench and the centre of mass of a satellite, the TTL noise of the new off-axis optical bench design may be suppressed efficiently. Full article

With the rising incidence of hepatocellular carcinoma (HCC) from non-alcoholic steatohepatitis (NASH), identifying new metabolic readouts that function in metabolic pathway perpetuation is still a demand. The study aimed to compare the metabolic signature between NASH and NASH-HCC patients to explore novel reprogrammed metabolic pathways that might modulate cancer progression in NASH patients. NASH and NASH-HCC patients were recruited and screened for metabolomics, and isotope-labeled lipidomics were targeted and profiled using the EXION-LCTM system equipped with a Triple-TOFTM 5600+ system. Results demonstrated significantly (p ≤ 0.05) higher levels of triacylglycerol, AFP, AST, and cancer antigen 19-9 in NASH-HCC than in NASH patients, while prothrombin time, platelet count, and total leukocyte count were decreased significantly (p ≤ 0.05). Serum metabolic profiling showed a panel of twenty metabolites with 10% FDR and p ≤ 0.05 in both targeted and non-targeted analysis that could segregate NASH-HCC from NASH patients. Pathway analysis revealed that the metabolites are implicated in the down-regulation of necroptosis, amino acid metabolism, and regulation of lipid metabolism by PPAR-α, biogenic amine synthesis, fatty acid metabolism, and the mTOR signaling pathway. Cholesterol metabolism, DNA repair, methylation pathway, bile acid, and salts metabolism were significantly upregulated in NASH-HCC compared to the NASH group. Metabolite–protein interactions network analysis clarified a set of well-known protein encoding genes that play crucial roles in cancer, including PEMT, IL4I1, BAAT, TAT, CDKAL1, NNMT, PNP, NOS1, and AHCYL. Taken together, reliable metabolite fingerprints are presented and illustrated in a detailed map for the most predominant reprogrammed metabolic pathways that target HCC development from NASH. Full article

d-Allulose is the corresponding epimer of d-fructose at the C-3 position, which exhibits a similar taste and sweetness to sucrose. As a low-calorie sweetener, d-allulose has broad application prospects in the fields of medicine, food, and so on. Currently, the production method of d-allulose is mainly the enzymatic conversion of d-fructose by d-allulose 3-epimerase (DAEase). However, the limited specific activity and thermal stability of DAEase restrict its industrial application. Herein, an ultrahigh-throughput screening assay based on the transcription factor PsiR was extensively optimized from the aspects of culture medium components, screening plasmid, and expression host, which enhanced the correction between the fluorescent readout and the enzyme activity. Then, the error-prone PCR (epPCR) library of Clostridium cellulolyticum H10 DAEase (CcDAEase) was screened through the above optimized method, and the variant I228V with improved specific activity and thermal stability was obtained. Moreover, after combining two beneficial substitutions, D281G and C289R, which were previously obtained by this optimized assay, the specific activity of the triple-mutation variant I228V/D281G/C289R reached up to 1.42-fold of the wild type (WT), while its half-life (T_1/2) at 60 °C was prolonged by 62.97-fold. The results confirmed the feasibility of the optimized screening assay as a powerful tool for the directed evolution of DAEase. Full article

Metabolic reprogramming and genomic instability are key hallmarks of cancer, the combined analysis of which has gained recent popularity. Given the emerging evidence indicating the role of oncometabolites in DNA damage repair and its routine use in breast cancer treatment, it is timely to fingerprint the impact of olaparib treatment in cellular metabolism. Here, we report the biomolecular response of breast cancer cell lines with DNA damage repair defects to olaparib exposure. Following evaluation of olaparib sensitivity in breast cancer cell lines, we immunoprobed DNA double strand break foci and evaluated changes in cellular metabolism at various olaparib treatment doses using untargeted mass spectrometry-based metabolomics analysis. Following identification of altered features, we performed pathway enrichment analysis to measure key metabolic changes occurring in response to olaparib treatment. We show a cell-line-dependent response to olaparib exposure, and an increased susceptibility to DNA damage foci accumulation in triple-negative breast cancer cell lines. Metabolic changes in response to olaparib treatment were cell-line and dose-dependent, where we predominantly observed metabolic reprogramming of glutamine-derived amino acids and lipids metabolism. Our work demonstrates the effectiveness of combining molecular biology and metabolomics studies for the comprehensive characterisation of cell lines with different genetic profiles. Follow-on studies are needed to map the baseline metabolism of breast cancer cells and their unique response to drug treatment. Fused with genomic and transcriptomics data, such readout can be used to identify key oncometabolites and inform the rationale for the design of novel drugs or chemotherapy combinations. Full article

Temperature is one of the most relevant physical quantities that affects almost all processes in nature. However, the realization of accurate temperature standards using current temperature references, like the triple point of water, is difficult due to the requirements on material purity and stability of the environment. In addition, in harsh environments, current temperature sensors with electrical readout, like platinum resistors, are difficult to implement, urging the development of optical temperature sensors. In 2018, the European consortium Photoquant, consisting of metrological institutes and academic partners, started investigating new temperature standards for self-calibrated, embedded optomechanical sensor applications, as well as optimised high resolution and high reliability photonic sensors, to measure temperature at the nano and meso-scales and as a possible replacement for the standard platinum resistant thermometers. This article presents an overview of the results obtained with sensor prototypes that exploit photonic and optomechanical techniques for sensing temperatures over a large temperature range (5 K to 300 K). Different concepts are demonstrated, including ring resonators, ladder-like resonators and suspended membrane optomechanical thermometers, highlighting initial performance and challenges, like self-heating that need to be overcome to realize photonic and optomechanical thermometry applications. Full article

The BESIII experiment has been collecting data since 2009 at the e${}^{+}$e${}^{-}$ collider BEPCII in Beijing, a charm-$\tau$ factory characterized by high statistics and high precision. The discovery of exotic charmonium-like states and the still open questions in low-energy QCD led to an extension of the experimental program, with several upgrades. This review focuses on the CGEM-IT, the innovative solution proposed to replace the current inner tracker, which is aging. It consists of three, co-axial, cylindrical triple-GEM detectors and will be the first cylindrical GEM operating inside a 1 T magnetic field with analogue readout. For this purpose, a dedicated mixed-signal ASIC for the readout of CGEM-IT signals and FPGA-based electronics for data processing have been developed. The simultaneous measurement of both ionization charge and time distribution enables three reconstruction algorithms, to cope with the asymmetry of the electron avalanche in the magnetic field and with non-orthogonal incident tracks. The CGEM-IT will not only restore the design efficiency but also improve the secondary vertex reconstruction and the radiation tolerance. The gas mixture and gain settings were chosen to optimize the position resolution to ∼130 µm in the transverse plane and better than 350 µm along the beam direction. This paper addresses the innovative aspects in terms of construction, readout, and software, employed to achieve the design goals as well as the experimental measurements performed during the development and commissioning of the CGEM-IT. Full article

This paper presents the LC-type passive wireless sensing system for the simultaneous and independent detection of triple parameters, featuring three different capacitive sensors controlled by two mechanical switches. The sensor coil was connected with three different capacitors in parallel and two mechanical switches were in series between every two capacitors, which made the whole system have three resonant frequencies. The readout coil was magnetically coupled with the sensor coil to interrogate the sensor wirelessly. The circuit was simulated advanced design system (ADS) software, and the LC sensor system was mathematically analyzed by MATLAB. Results showed that the proposed LC sensing system could test three different capacitive sensors by detecting three different resonant frequencies. The sensitivity of sensors could be determined by the capacitance calculated from the detected resonant frequencies, and the resolution of capacitance was 0.1 PF and 0.2 PF when using the proposed sensor system in practical applications. To validate the proposed scheme, a PCB inductor and three variable capacitors were constructed with two mechanical switches to realize the desired system. Experimental results closely verified the simulation outputs. Full article

Quality Assurance (QA) in hadron therapy is crucial to ensure safe and accurate dose delivery to patients. This can be achieved with fast, reliable and high-resolution detectors. In this paper, we present a novel solution that combines a triple Gas Electron Multiplier (GEM) and a highly pixelated readout based on a matrix of organic photodiodes fabricated on top of an oxide-based thin-film transistor backplane. The first LaGEMPix prototype with an active area of 60 × 80 mm² was developed and characterized using low energy X-rays. The detector comprises a drift gap of 3.5 mm, a triple-GEM stack for electron amplification, and a readout featuring 480 × 640 pixels at a 126 µm pitch. Here, we describe the measurements and results in terms of spatial resolution for various experimental configurations. A comparison with GAFCHROMIC^® films and the GEMPix detector used in the charge readout mode was performed to better understand the contribution to the spatial resolution from both the electron diffusion and the isotropic emission of photons. The measurements were compared to Monte Carlo simulations, using the FLUKA code. The simulation predictions are in good agreement with the GEMPix results. Future plans with respect to applications in hadron therapy are discussed. Full article

As a commonly used solution, the multi-ended readout can measure the depth-of-interaction (DOI) for positron emission tomography (PET) detectors. In the present study, the effects of the multi-ended readout design were investigated using the leading-edge discriminator (LED) triggers on the timing performance of time-of-flight (TOF) PET detectors. At the very first, the photon transmission model of the four detectors, namely, single-ended readout, dual-ended readout, side dual-ended readout, and triple-ended readout, was established in Tracepro. The optical simulation revealed that the light output of the multi-ended readout was higher. Meanwhile, the readout circuit could be triggered earlier. Especially, in the triple-ended readout, the light output at 0.5 ns was observed to be nearly twice that of the single-ended readout after the first scintillating photon was generated. Subsequently, a reference detector was applied to test the multi-ended readout detectors that were constructed from a 6 × 6 × 25 mm³ LYSO crystal. Each module is composed of a crystal coupled with multiple SiPMs. Accordingly, its timing performance was improved by approximately 10% after the compensation of fourth-order polynomial fitting. Finally, the compensated full-width-at-half-maximum (FWHM) coincidence timing resolutions (CTR) of the dual-ended readout, side dual-ended readout, and triple-ended readout were 216.9 ps, 231.0 ps, and 203.6 ps, respectively. Full article

In current food safety monitoring, lateral flow immunoassays (LFIAs) are widely used for rapid food contaminant screening. Recent advances include smartphone readouts, offering semi-quantitative analysis of LFIAs with time, location, and data transfer in case of on-site testing. Following the screening, the next step in the EU regulations is confirmation by, e.g., liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this work, using direct analysis in real time ambient ionization and triple quadrupole MS/MS (DART-QqQ-MS/MS), we achieved rapid confirmation of the identity of the substance(s) causing the LFIA result. In the workflow proposed, an individual performs the (on-site) smartphone LFIA screening, and when the result is suspect, an identification LFIA (ID-LFIA) strip is developed with the same sample extract. The ID-LFIA can be dissociated and rapidly analyzed in a control laboratory with DART-QqQ-MS/MS. The ID-LFIA consists of multiple lines of monoclonal antibodies against the mycotoxin deoxynivalenol, acting as a bioaffinity trap. The ID-LFIA/DART-QqQ-MS/MS approach has been developed and validated, along with the screening smartphone LFIA, and has demonstrated its applicability by analyzing incurred and spiked samples. The developed approach has been critically compared with our previous direct electrospray ionization MS method and was found to provide highly complementary information on the total deoxynivalenol contamination in the sample. Full article

There is momentum in biomedical research to improve the structure and function of in vitro intestinal models that better represent human biology. To build a more comprehensive model, three human cell-types were co-cultured and characterized: i.e., HT29-MTX (intestinal mucous-producing goblet cells), Caco-2 (colon epithelial cells), and Raji B (lymphocytes). Raji B cells transformed a subpopulation of Caco-2 epithelial cells into phagocytic and transcytotic immune-supporting microfold cells (M-cells). A suite of bioassays was implemented to investigate steady-state barrier integrity and cellular communication. The model demonstrated a potentiating effect in metabolism and pro-inflammatory markers. Barrier integrity and cell seeding density seem to play a role in the reliability of endpoint readouts. Microscopic analysis elucidated the importance of multi-cell biomimicry. The data show that monocultures do not have the same characteristics inherent to triple cell culture models. Multiple cell types in an in vitro model produce a better representation of an intact organ and aid in the ability to assess immunomodulatory effects of nanomaterials designed for cancer theranostics after ingestion. As many national and international agencies have stressed, there is a critical need to improve alternative-to-animal strategies for pharmaceuticals in an effort to reduce animal testing. Full article