Screening Technologies Research Articles

High‐Throughput Screening Technologies of Efficient Catalysts for The Ammonia Economy

Driven by the growing global demand for sustainable energy, ammonia is gaining recognition as a crucial energy carrier with the potential for widespread manufacturing. This has spurred the emergence of a "sustainable ammonia economy." Efficient catalyst development is paramount to achieving this purpose. Although the traditional trial‐and‐error methods have led to substantial progress, they are inherently time‐consuming. In recent years, the high‐throughput screening strategies are revolutionizing catalyst discovery, offering an efficient and cost‐effective approach for identifying high‐performance catalysts across various processes within the ammonia economy. This review explores recent advancements in these rapid catalyst screening techniques for ammonia‐based processes. By outlining the general screening principles and the key steps involved in the computational analysis of catalysts relevant to different stages of the ammonia economy, this review aims to provide fundamental insights for the development of novel catalysts using these accelerated methods.

No Ear Left Behind: Wireless Earbuds for Low-Cost Hearing Screening

Hearing loss is particularly harmful for language acquisition and neuro-development if it is left undetected in early childhood. Newborn hearing screening technologies using otoacoustic emissions (OAE) rely on detecting soft sounds generated by a healthy cochlea. High-income countries like the United States frequently implement hearing screening programs for every child at birth. However, such universal hearing screening is significantly less common in low- and middle-income countries, partly due to the conventional wisdom that the test requires sensitive and expensive acoustic hardware that costs thousands of dollars. In our MobiSys paper[1], we present the first wireless earbud design for low-cost hearing screening. Our hardware-software system reliably performs hearing screening using low-cost acoustic hardware, while being in the form-factor of a wireless earbud (Figure. 1a,b). The earbud hardware is designed to work across a large age range from newborns to adults. By developing low-cost and open-source wearable technology, our work may help address global health inequities in hearing screening by democratizing these medical devices.

Feasibility of snapshot testing using wearable sensors to detect cardiorespiratory illness (COVID infection in India).

The COVID-19 pandemic has challenged the current paradigm of clinical and community-based disease detection. We present a multimodal wearable sensor system paired with a two-minute, movement-based activity sequence that successfully captures a snapshot of physiological data (including cardiac, respiratory, temperature, and percent oxygen saturation). We conducted a large, multi-site trial of this technology across India from June 2021 to April 2022 amidst the COVID-19 pandemic (Clinical trial registry name: International Validation of Wearable Sensor to Monitor COVID-19 Like Signs and Symptoms; NCT05334680; initial release: 04/15/2022). An Extreme Gradient Boosting algorithm was trained to discriminate between COVID-19 infected individuals (n = 295) and COVID-19 negative healthy controls (n = 172) and achieved an F1-Score of 0.80 (95% CI = [0.79, 0.81]). SHAP values were mapped to visualize feature importance and directionality, yielding engineered features from core temperature, cough, and lung sounds as highly important. The results demonstrated potential for data-driven wearable sensor technology for remote preliminary screening, highlighting a fundamental pivot from continuous to snapshot monitoring of cardiorespiratory illnesses.

Single-cell technology for drug discovery and development

The success rate of drug development today remains low, with long development cycles and high costs, especially in areas such as oncology, neurology, immunology, and infectious diseases. Single-cell omics, encompassing transcriptomics, genomics, epigenomics, proteomics, and metabolomics enable the analysis of gene expression profiles and cellular heterogeneity from the perspective of individual cells, offering a high-resolution view of their functional diversity. These technologies can help reveal disease mechanisms, drug target identification and validation, selection of preclinical models and candidate drugs, and clinical decision-making based on disease response to drugs, all at the single-cell level. The development of deep learning technology has provided a powerful tool for research in drug discovery based on single-cell techniques, which has evolved with the advent of large-scale public databases to predict drug responses and targets. In addition, traditional Chinese medicine (TCMs) research has also entered the era of single-cell technology. Single-cell omics technologies offer an alternative way in deciphering the mechanisms of TCMs in disease treatment, revealing drug targets, screening new drugs, and designing combinations of TCMs. This review aims to explore the application of single-cell omics technologies in drug screening and development comprehensively, highlighting how they accelerate the drug development process and facilitate personalized medicine by precisely identifying therapeutic targets, predicting drug responsiveness, deciphering mechanisms of action. It is also concluded that drug development process and therapeutic efficacy of drugs can be improved by combining single-cell omics and artificial intelligence techniques.

Anti-OAcGD2 antibody in combination with ceramide kinase inhibitor mediates potent antitumor cytotoxicity against breast cancer and diffuse intrinsic pontine glioma cells.

O-acetylated GD2 (OAcGD2) is a cancer-related antigen that is currently being explored for therapeutic use. Exploring the intricate mechanisms behind OAcGD2 synthesis in cancer cells has long been a challenge. Leveraging state-of-the-art high-throughput RNAi screening and confocal imaging technologies, our study delves into the genetic network orchestrating OAcGD2 synthesis in breast cancer cells. By conducting a comprehensive siRNA screen targeting the OAcGD2 phosphatome/kinome, we identified 43 genetic modulators, with 25 downregulating and 18 upregulating OAcGD2 synthesis. Among these, our study focused on CERK, the gene-encoding ceramide kinase, a pivotal player in glycosphingolipid metabolism. Through meticulous experimentation utilizing anti-CERK inhibitor and siRNAs, we made a significant discovery: CERK inhibition robustly upregulates OAcGD2 in both neuroblastoma and breast cancer cells, concurrently dampening cell migration. Furthermore, our findings highlight an exciting prospect: augmenting the antibody-dependent cell cytotoxicity of the chimeric human/mouse anti-OAcGD2 IgG1 monoclonal antibody (c8B6 mAb) against breast cancer and diffuse intrinsic pontine glioma cell lines in combination with specific CERK inhibitors. These results underscore the pivotal role of CERK inhibition in bolstering OAcGD2 synthesis, thus, presenting a promising strategy to increase the efficacy of anti-OAcGD2-based immunotherapy in patients with neuroectodermal tumors. By shedding light on this intricate interplay, our study paves the way for innovative therapeutic strategies poised to revolutionize the treatment landscape for these aggressive malignancies.

Time on task effects during interactive visual search.

There is a major shift taking place in airports across the globe, changing from 2D dual-view X-ray screening to 3D computed tomography (CT) screening. 3D CT screening is believed to improve target detection since it enables screeners to interact with images of passenger baggage (i.e., rotating and zooming into the displays). The change in screening technology is moving what was once a purely visual search task to an interactive search task. Here, we conducted two experiments with a large sample size during February of 2023 (695 participants) to examine (a) changes in search performance between a simulated dual-view and simulated interactive search task and (b) the effects of time on task upon performance. Consistent with past research, we found that interactive search, when compared with dual-view search, produced higher response accuracy rates coupled with increased reaction times (RTs). However, while we found effects of time on task (RTs reduced, and participants became more likely to respond "absent" as the experiments progressed), there was no evidence that these effects differed across simulated dual-view and simulated interactive searches. The results are discussed in relation to benefits of interactive search for supporting target detection by airport screeners. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Public engagement with consumer sleep technology for obstructive sleep apnea screening: implications for equity, access, and practice.

To characterize public practices and perspectives on the use of consumer sleep technology (CST) and evaluate perspectives on using CST as a screening tool for obstructive sleep apnea (OSA). We designed a survey instrument incorporating content from validated instruments (STOP-BANG and the Epworth Sleepiness Scale) and hypothesis-generated questions. Survey development involved multidisciplinary collaboration among three board-certified sleep medicine experts, researchers, and consumers. The survey was disseminated across a national sample of adults living in the United States via an online platform. Among 897 respondents, the mean (SD) age was 47.5 (16.9) years; 73.1% were female, 81.8% were White, and 505 respondents (56.3%) reported having tracked sleep using CS. Factors associated with decreased odds of CST use included household income <$30,000 (OR 0.47, 95% CI 0.28-0.79; p=0.004), Medicaid insurance (OR 0.43, 95% CI 0.26-0.69; p=0.001), Medicare insurance (OR 0.59, 95% CI 0.41-0.84; p=0.004), and lack of a primary care physician (OR 0.55, 95% CI 0.33-0.91; p=0.021). Most respondents (91.1%) agreed or strongly agreed that screening for OSA would be a useful feature of CST, but respondents reporting an education of high school diploma or less (OR 0.48, 95% CI 0.29-0.79; p=0.004) were less likely to agree with this statement. Attitudes toward and use of CST differed based on demographic and socioeconomic factors. Further study is needed to understand and address barriers to CST adoption and to characterize implications for equitable access to care for sleep disorders.

Expert consensus on the clinical application strategy of NIPT2.0, a new-generation non-invasive prenatal screening technology

The new-generation non-invasive prenatal screening technology (NIPT2.0) is a new method successfully realized in recent years based on high-throughput sequencing to synchronously and accurately detect fetal chromosomal aneuploidies, microdeletion/microduplication syndromes and dominantly inherited monogenic disorders. NIPT2.0 can circumvent the shortcomings of previous non-invasive prenatal screening techniques (NIPT and NIPT Plus) including incapability to detect fetal monogenic disorders, insufficient accuracy of detection and low positive predictive values for certain chromosomal abnormalities (in particular trisomy 13, sex chromosomal abnormalities, and small-segment microdeletions and microduplication syndromes). How to apply NIPT2.0 reasonably and normatively to maximize its clinical value has become an issue which requires clarification. The Reproductive Health Branch of the Chinese Maternal and Child Health Care Association and the Genetic Diagnosis Branch of the Genetics Society of China have organized experts to fully discuss and jointly drafted this consensus, which has put forwards suggestions over the clinical application strategy for NIPT2.0, including the scope of application, target disease, pre-test consultation, clinical application pathway, post-test genetic counseling and intervention, quality control and limitations, for the reference by peers, with a view to standardize its application and provide better clinical service.

Reassessing Cervical Cancer Prevention: Evaluating the NHS Cervical Cancer Screening Programme Through the Health Belief Model and Global Health Promotion Strategies

Cervical cancer remains a significant public health issue in the United Kingdom, with disparities in screening coverage and outcomes persisting despite robust national programs. This critical analysis evaluates the NHS Cervical Screening Programme (CSP) through the lens of the Health Belief Model (HBM) and global health promotion strategies, such as those outlined in the Ottawa Charter. The analysis explores how individual beliefs about susceptibility, severity, benefits, and barriers influence participation in cervical screening, while also critiquing the CSP's reliance on these factors to the potential exclusion of broader social determinants of health. Key findings reveal that while the HBM provides a valuable framework for understanding individual health behaviors, its emphasis on personal responsibility may overlook significant socioeconomic and cultural barriers, leading to inequities in screening uptake. Furthermore, the CSP's approach, though well-intentioned, may inadvertently undermine patient autonomy by promoting a top-down model of health promotion. The analysis is supported by data from the 2022-2023 Cervical Screening Standards Data Report and other contemporary sources, highlighting the need for more culturally sensitive and equitable strategies. Recommendations for policymakers include the enhancement of targeted interventions for high-risk groups, improved communication strategies, and the integration of a social model of health that considers the broader determinants of health. Future studies are encouraged to explore the sociocultural factors influencing screening behaviors and to evaluate the effectiveness of new screening technologies and integrated HPV vaccination programs. This analysis underscores the importance of rethinking cervical cancer prevention strategies to ensure they are inclusive, equitable, and aligned with the principles of health promotion.

372 (PB360): Discovery of a highly MTA-synergistic series of PRMT5 inhibitors for the treatment of MTAP-deficient tumors by virtual screening technology

372 (PB360): Discovery of a highly MTA-synergistic series of PRMT5 inhibitors for the treatment of MTAP-deficient tumors by virtual screening technology

Exploring the Artificial Intelligence and Its Impact in Pharmaceutical Sciences: Insights Toward the Horizons Where Technology Meets Tradition.

The technological revolutions in computers and the advancement of high-throughput screening technologies have driven the application of artificial intelligence (AI) for faster discovery of drug molecules with more efficiency, and cost-friendly finding of hit or lead molecules. The ability of software and network frameworks to interpret molecular structures' representations and establish relationships/correlations has enabled various research teams to develop numerous AI platforms for identifying new lead molecules or discovering new targets for already established drug molecules. The prediction of biological activity, ADME properties, and toxicity parameters in early stages have reduced the chances of failure and associated costs in later clinical stages, which was observed at a high rate in the tedious, expensive, and laborious drug discovery process. This review focuses on the different AI and machine learning (ML) techniques with their applications mainly focused on the pharmaceutical industry. The applications of AI frameworks in the identification of molecular target, hit identification/hit-to-lead optimization, analyzing drug-receptor interactions, drug repurposing, polypharmacology, synthetic accessibility, clinical trial design, and pharmaceutical developments are discussed in detail. We have also compiled the details of various startups in AI in this field. This review will provide a comprehensive analysis and outline various state-of-the-art AI/ML techniques to the readers with their framework applications. This review also highlights the challenges in this field, which need to be addressed for further success in pharmaceutical applications.

A Triple-Mismatch Differentiating assay exploiting activation and trans cleavage of CRISPR-Cas12a for mutation detection with ultra specificity and sensitivity

Liquid biopsy technology is non-invasive and convenient, and is currently an emerging technology for cancer screening. Among them, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 12a (Cas12a) based nucleic acid detection technology has the advantages of high sensitivity, rapidity, and easy operation. However, CRISPR-Cas12a does not discriminate single-base mismatches of targets well enough to meet the needs of clinical detection. Herein, we developed the Triple-Mismatch Differentiating (TMD) assay. This assay amplified the small thermodynamic difference in mismatches at one site at the level of CRISPR-Cas12a activation to a significant thermodynamic difference at three sites at both the level of CRISPR-Cas12a activation and trans-cleavage, which greatly improves the ability of CRISPR-Cas12a to discriminate between base mismatches. Our manipulation greatly improved the specificity of the CRISPR-Cas12a system while maintaining its inherent sensitivity and simplicity, increasing the detection limit to 0.0001%. When testing samples from pancreatic cancer patients, our results were highly consistent with NGS sequencing results. We believe that the TMD assay will provide a new technology for early cancer detection and will be widely used in the clinical practice.

Findings from the individualized management of a patient with Acyl-CoA Oxidase-1 (ACOX1) deficiency: A bedside-to-bench-to-bedside strategy

Acyl-CoA Oxidase-1 (ACOX1) deficiency (MIM 264470) is an autosomal recessive disease characterized by impairments in the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, which is the first step in the catalysis of the β-oxidative breakdown of very long chain fatty acids (VLCFA) occuring in peroxisomes. The deleterious accumulation of VLCFA in several organs, including the brain, is a key biochemical feature of this disease which has devastating neurological consequences. ACOX1 deficiency is ultra-rare; as such, few studies have been conducted to determine the leading causes of symptoms or uncover new therapeutics. When confronted with one such case, we decided to bring drug discovery tools to the patient's bedside in an attempt to identify a cure. A skin biopsy was performed on a young patient with ACOX1 deficiency, following which screening technologies and mass spectrometry analysis techniques were applied to design a cellular assay that enabled the direct measurement of the effect of small molecules on the patient's primary fibroblasts. This approach is particularly well adapted to inherited metabolic disorders such as ACOX1 deficiency. Through the evaluation of a proprietary library of repurposable drugs, we found that the anthelmintic drug niclosamide led to a significant reduction in VLCFA in vitro. This drug was subsequently administered to the patient for more than six years. This study outlines the screening and drug selection processes. Additionally, we present our comprehensive clinical and biochemical findings that aided in understanding the patient's natural history and analysis of the progression of the patient's symptoms throughout the treatment period. Although the patient's overall lifespan was extended compared to the average age at death in severe early onset cases of ACOX1 deficiency, we did not observe any definitive evidence of clinical or biochemical improvement during niclosamide treatment. Nonetheless, our study shows a good safety profile of long-term niclosamide administration in a child with a rare neurodegenerative disease, and illustrates the potential of individualized therapeutic strategies in the management of inherited metabolic disorders, which could benefit both patients and the broader scientific and medical communities.

Prenatal testing technologies in Australia: Unintended clinical and emotional complexities in underprepared systems

The past decade has seen technological advances in prenatal screening technologies rapidly integrated into clinical practice. These technologies have revolutionised healthcare and raised complex socio-ethical issues such as equitable access, medical commercialisation, and new eugenics. However, the important issue of the impact of these technologies on healthcare professionals is receiving less attention. Exploring this issue in the Australian context, we conducted a survey from August to November 2022, targeting health and allied health professionals who work with parents in the perinatal period who have received a fetal diagnosis. We received 75 substantive responses from a diversity of professionals, including sonographers, midwives, genetic counsellors and medical providers.In this article, we consider the unintended impacts of prenatal screening technologies on healthcare workers, drawing from Ziebland et al., ’s 2021 unintended consequences framework. Our reflexive thematic analysis produced three key themes: “Unintended Clinical Complexities”, “Adapting Work Practices to Keep Up in Systems that Lack”, and “Unintended Intensification of Emotional Labour”. Prenatal testing technologies have intentionally increased early testing and fetal information, offering veiled promises of increased certainty in pregnancy. However, our analysis highlights that these advancing technologies also generate more ambiguous results, creating unintended clinical and emotional complexities for healthcare providers. Workers must manage increased clinical uncertainty and constant change, creating intensified emotional labour in under-prepared systems. We conclude by identifying the need to recognise the impacts of advancing prenatal screening technologies on healthcare workers and for targeted professional training to prepare healthcare professionals for the complexities introduced by these new technologies.

Utilizing a high-throughput visualization screening technology to develop a genetically encoded biosensor for monitoring 5-aminolevulinic acid production in engineered Escherichia coli

5-Aminolevulinic acid (5-ALA) is a non-protein amino acid widely used in agriculture, animal husbandry and medicine. Currently, microbial cell factories are a promising production pathway, but the lack of high-throughput fermentation strain screening tools often hinders the exploration of engineering strategies to increase cell factory yields. Here, mutant AC103-3H was screened from libraries of saturating mutants after response-specific engineering of the transcription factor AsnC of L-asparagine (Asn). Based on mutant AC103-3H, a whole-cell biosensor EAC103-3H with a specific response to 5-ALA was constructed, which has a linear dynamic detection range of 1–12 mM and a detection limit of 0.094 mM, and can be used for in situ screening of potential high-producing 5-ALA strains. With its support, overexpression of the C5 pathway genes using promoter engineering assistance resulted in a 4.78-fold enhancement of 5-ALA production in the engineered E. coli. This study provides an efficient strain screening tool for exploring approaches to improve the 5-ALA productivity of engineered strains.

Advancements in mammalian display technology for therapeutic antibody development and beyond: current landscape, challenges, and future prospects.

The evolving development landscape of biotherapeutics and their growing complexity from simple antibodies into bi- and multi-specific molecules necessitates sophisticated discovery and engineering platforms. This review focuses on mammalian display technology as a potential solution to the pressing challenges in biotherapeutic development. We provide a comparative analysis with established methodologies, highlighting key aspects of mammalian display technology, including genetic engineering, construction of display libraries, and its pivotal role in hit selection and/or developability engineering. The review delves into the mechanisms underpinning developability-driven selection via mammalian display and their broader implications. Applications beyond antibody discovery are also explored, alongside advancements towards function-first screening technologies, precision genome engineering and AI/ML-enhanced libraries, situating them in the context of mammalian display. Overall, the review provides a comprehensive overview of the current mammalian display technology landscape, underscores the expansive potential of the technology for biotherapeutic development, addresses the critical challenges for the full realisation of this potential, and examines advances in related disciplines that might impact the future application of mammalian display technologies.

Mid-infrared chemical imaging of living cells enabled by plasmonic metasurfaces.

Mid-Infrared (MIR) chemical imaging provides rich chemical information of biological samples in a label-free and non-destructive manner. Yet, its adoption to live-cell analysis is limited by the strong attenuation of MIR light in water, often necessitating cell culture geometries that are incompatible with the prolonged viability of cells and with standard high-throughput workflow. Here, we introduce a new approach to MIR microscopy, where cells are imaged through their localized near-field interaction with a plasmonic metasurface. Chemical contrast of distinct molecular groups provided sub-cellular resolution images of the proteins, lipids, and nucleic acids in the cells that were collected using an inverted MIR microscope. Time-lapse imaging of living cells demonstrated that their behaviors, including motility, viability, and substrate adhesion, can be monitored over extended periods of time using low-power MIR light. The presented approach provides a method for the non-perturbative MIR imaging of living cells, which is well-suited for integration with modern high-throughput screening technologies for the label-free, high-content chemical imaging of living cells.

Correlating NAD(P)H lifetime shifts to tamoxifen resistance in breast cancer cells: A metabolic screening study with time-resolved flow cytometry

Time-resolved flow cytometry (TRFC) was used to measure metabolic differences in estrogen receptor-positive breast cancer cells. This specialty cytometry technique measures fluorescence lifetimes as a single-cell parameter thereby providing a unique approach for high-throughput cell counting and screening. Differences in fluorescence lifetime were detected and this was associated with sensitivity to the commonly prescribed therapeutic tamoxifen. Differences in fluorescence lifetime are attributed to the binding states of the autofluorescent metabolite NAD(P)H. The function of NAD(P)H is well described and in general involves cycling from a reduced to oxidized state to facilitate electron transport for the conversion of pyruvate to lactate. NAD(P)H fluorescence lifetimes depend on the bound or unbound state of the metabolite, which also relates to metabolic transitions between oxidative phosphorylation and glycolysis. To determine if fundamental metabolic profiles differ for cells that are sensitive to tamoxifen compared to those that are resistant, large populations of MCF-7 breast cancer cells were screened and fluorescence lifetimes were quantified. Additionally, metabolic differences associated with tamoxifen sensitivity were measured with a Seahorse HS mini metabolic analyzer (Agilent Technologies Inc. Santa Clara, CA) and confocal imaging. Results show that tamoxifen-resistant breast cancer cells have increased utilization of glycolysis for energy production compared to tamoxifen-sensitive breast cancer cells. This work is impacting because it establishes an early step toward developing a reliable screening technology in which large cell censuses can be differentiated for drug sensitivity in a label-free fashion.

Research on Vibrating Screen Screening Technology and Method Based on DEM: a Review

Research on Vibrating Screen Screening Technology and Method Based on DEM: a Review

Spectral induced polarization (SIP) measurements across a PFAS-contaminated source zone

There is a need to develop field-scale, in situ screening technologies for assessing variations in aqueous film-forming foam (AFFF) concentrations in soils at former fire training and storage sites. Field-scale Spectral Induced Polarization (SIP) geophysical measurements were acquired on a transect crossing an AFFF source zone. Soil samples were acquired to determine variations in poly- and per-fluoroalkyl substances (PFAS) concentrations in soils, characterize soil texture, and create triplicate soil columns for laboratory SIP measurements. Field and laboratory observations show that SIP measurements are sensitive to the concentration of AFFF constituents associated with soil pore surface area. The specific polarizability and the phase of the SIP measurements for the laboratory samples were linearly correlated with total soil-sorbed PFAS concentration. The phase from the field SIP measurements was highest over the location of maximum PFAS concentration measured on the laboratory samples. However, a significant correlation between field-measured phase and laboratory-measured total PFAS concentration still needs to be established. These observations, along with the demonstrated sensitivity of the SIP response to the removal of soil PFAS using a methanol wash procedure, support the case for SIP characterization of AFFF source zones.