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This study explores the fusion of a field-effect transistor (FET), a paper-based analytical cartridge, and the computational power of deep learning (DL) for quantitative biosensing via kinetic analyses. The FET sensors address the low sensitivity challenge observed in paper analytical devices, enabling electrical measurements with kinetic data. The paper-based cartridge eliminates the need for surface chemistry required in FET sensors, ensuring economical operation (cost < $0.15/test). The DL analysis mitigates chronic challenges of FET biosensors such as sample matrix interference, by leveraging kinetic data from target-specific bioreactions. In our proof-of-concept demonstration, our DL-based analyses showcased a coefficient of variation of <6.46% and a decent concentration measurement correlation with an r 2 value of >0.976 for cholesterol testing when blindly compared to results obtained from a CLIA-certified clinical laboratory. These integrated technologies have the potential to advance FET-based biosensors, potentially transforming point-of-care diagnostics and at-home testing through enhanced accessibility, ease-of-use, and accuracy.

Successful integration of point-of-care testing (POCT) into clinical settings requires improved assay sensitivity and precision to match laboratory standards. Here, we show how innovations in amplified biosensing, imaging, and data processing, coupled with deep learning, can help improve POCT. To demonstrate the performance of our approach, we present a rapid and cost-effective paper-based high-sensitivity vertical flow assay (hs-VFA) for quantitative measurement of cardiac troponin I (cTnI), a biomarker widely used for measuring acute cardiac damage and assessing cardiovascular risk. The hs-VFA includes a colorimetric paper-based sensor, a portable reader with time-lapse imaging, and computational algorithms for digital assay validation and outlier detection. Operating at the level of a rapid at-home test, the hs-VFA enabled the accurate quantification of cTnI using 50 μL of serum within 15 min per test and achieved a detection limit of 0.2 pg/mL, enabled by gold ion amplification chemistry and time-lapse imaging. It also achieved high precision with a coefficient of variation of <7% and a very large dynamic range, covering cTnI concentrations over 6 orders of magnitude, up to 100 ng/mL, satisfying clinical requirements. In blinded testing, this computational hs-VFA platform accurately quantified cTnI levels in patient samples and showed a strong correlation with the ground truth values obtained by a benchtop clinical analyzer. This nanoparticle amplification-based computational hs-VFA platform can democratize access to high-sensitivity point-of-care diagnostics and provide a cost-effective alternative to laboratory-based biomarker testing.

This study developed an innovative approach that combines a colourimetric sensor array (CSA) composed of twelve pH-response dyes with advanced algorithms, aiming to detect amine gases and assess the freshness of chilled beef. With the assistance of multivariate statistical analysis, the sensor array can effectively distinguish five amine gases and enable rapid quantification of trimethylamine vapour with a limit of detection (LOD) of 8.02 ppb and visually monitor the fresh levels of chilled beef. Moreover, the utilization of deep learning models (ResNet34, VGG16, and GoogleNet) for chilled beef freshness evaluation achieved an overall accuracy of 98.0 %. Furthermore, t-distributed stochastic neighbour embedding (t-SNE) visualized the feature extraction process and provided explanations to understand the classification process of deep learning. The results demonstrated that applying deep learning techniques in the process of pattern recognition of CSA can help in realizing the rapid, robust, and accurate assessment of chilled beef freshness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Health-related patient-reported outcomes (HR-PROs) are crucial for assessing the quality of life among individuals experiencing low back pain. However, manual data entry from paper forms, while convenient for patients, imposes a considerable tallying burden on collectors. In this study, we developed a deep learning (DL) model capable of automatically reading these paper forms., Methods: We employed the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, a globally recognized assessment tool for low back pain. The questionnaire comprised 25 low back pain-related multiple-choice questions and three pain-related visual analog scales (VASs). We collected 1305 forms from an academic medical center as the training set, and 483 forms from a community medical center as the test set. The performance of our DL model for multiple-choice questions was evaluated using accuracy as a categorical classification task. The performance for VASs was evaluated using the correlation coefficient and absolute error as regression tasks., Result: In external validation, the mean accuracy of the categorical questions was 0.997. When outputs for categorical questions with low probability (threshold: 0.9996) were excluded, the accuracy reached 1.000 for the remaining 65 % of questions. Regarding the VASs, the average of the correlation coefficients was 0.989, with the mean absolute error being 0.25., Conclusion: Our DL model demonstrated remarkable accuracy and correlation coefficients when automatic reading paper-based HR-PROs during external validation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Multiplexed computational sensing with a point-of-care serodiagnosis assay to simultaneously quantify three biomarkers of acute cardiac injury is demonstrated. This point-of-care sensor includes a paper-based fluorescence vertical flow assay (fxVFA) processed by a low-cost mobile reader, which quantifies the target biomarkers through trained neural networks, all within <15 min of test time using 50 µL of serum sample per patient. This fxVFA platform is validated using human serum samples to quantify three cardiac biomarkers, i.e., myoglobin, creatine kinase-MB, and heart-type fatty acid binding protein, achieving less than 0.52 ng mL -1 limit-of-detection for all three biomarkers with minimal cross-reactivity. Biomarker concentration quantification using the fxVFA that is coupled to neural network-based inference is blindly tested using 46 individually activated cartridges, which shows a high correlation with the ground truth concentrations for all three biomarkers achieving >0.9 linearity and <15% coefficient of variation. The competitive performance of this multiplexed computational fxVFA along with its inexpensive paper-based design and handheld footprint makes it a promising point-of-care sensor platform that can expand access to diagnostics in resource-limited settings., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Smartphone has long been considered as one excellent platform for disease screening and diagnosis, especially when combined with microfluidic paper-based analytical devices (μPADs) that feature low cost, ease of use, and pump-free operations. In this paper, we report a deep learning-assisted smartphone platform for ultra-accurate testing of paper-based microfluidic colorimetric enzyme-linked immunosorbent assay (c-ELISA). Different from existing smartphone-based μPAD platforms, whose sensing reliability is suffered from uncontrolled ambient lighting conditions, our platform is able to eliminate those random lighting influences for enhanced sensing accuracy. We first constructed a dataset that contains c-ELISA results (n = 2048) of rabbit IgG as the model target on μPADs under eight controlled lighting conditions. Those images are then used to train four different mainstream deep learning algorithms. By training with these images, the deep learning algorithms can well eliminate the influences of lighting conditions. Among them, the GoogLeNet algorithm gives the highest accuracy (>97%) in quantitative rabbit IgG concentration classification/prediction, which also provides 4% higher area under curve (AUC) value than that of the traditional curve fitting results analysis method. In addition, we fully automate the whole sensing process and achieve the "image in, answer out" to maximize the convenience of the smartphone. A simple and user-friendly smartphone application has been developed that controls the whole process. This newly developed platform further enhances the sensing performance of μPADs for use by laypersons in low-resource areas and can be facilely adapted to the real disease protein biomarkers detection by c-ELISA on μPADs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

During global outbreaks such as COVID-19, regular nucleic acid amplification tests (NAATs) have posed unprecedented burden on hospital resources. Data of traditional NAATs are manually analyzed post assay. Integration of artificial intelligence (AI) with on-chip assays give rise to novel analytical platforms via data-driven models. Here, we combined paper microfluidics, portable optoelectronic system with deep learning for SARS-CoV-2 detection. The system was quite streamlined with low power dissipation. Pixel by pixel signals reflecting amplification of synthesized SARS-CoV-2 templates (containing ORF1ab, N and E genes) can be real-time processed. Then, the data were synchronously fed to the neural networks for early prediction analysis. Instead of the quantification cycle (C q ) based analytics, reaction dynamics hidden at the early stage of amplification curve were utilized by neural networks for predicting subsequent data. Qualitative and quantitative analysis of the 40-cycle NAATs can be achieved at the end of 22nd cycle, reducing time cost by 45%. In particular, the attention mechanism based deep learning model trained by microfluidics-generated data can be seamlessly adapted to multiple clinical datasets including readouts of SARS-CoV-2 detection. Accuracy, sensitivity and specificity of the prediction can reach up to 98.1%, 97.6% and 98.6%, respectively. The approach can be compatible with the most advanced sensing technologies and AI algorithms to inspire ample innovations in fields of fundamental research and clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Medical imaging refers to the process of obtaining images of internal organs for therapeutic purposes such as discovering or studying diseases. The primary objective of medical image analysis is to improve the efficacy of clinical research and treatment options. Deep learning has revamped medical image analysis, yielding excellent results in image processing tasks such as registration, segmentation, feature extraction, and classification. The prime motivations for this are the availability of computational resources and the resurgence of deep convolutional neural networks. Deep learning techniques are good at observing hidden patterns in images and supporting clinicians in achieving diagnostic perfection. It has proven to be the most effective method for organ segmentation, cancer detection, disease categorization, and computer-assisted diagnosis. Many deep learning approaches have been published to analyze medical images for various diagnostic purposes. In this paper, we review the work exploiting current state-of-the-art deep learning approaches in medical image processing. We begin the survey by providing a synopsis of research works in medical imaging based on convolutional neural networks. Second, we discuss popular pretrained models and general adversarial networks that aid in improving convolutional networks' performance. Finally, to ease direct evaluation, we compile the performance metrics of deep learning models focusing on COVID-19 detection and child bone age prediction., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Bagher Sistaninejhad et al.)

Practical human biofluid sensing requires a sensor device to differentiate patients from the normal group with high sensitivity and specificity. Label-free molecular identification from human biofluids allows direct classification of abnormal samples, providing insights for disease diagnosis and finding of new biomarkers. Here, we introduce a label-free surface-enhanced Raman scattering sensor based on a three-dimensional plasmonic coral nanoarchitecture (3D-PCN), which has strong electromagnetic field enhancement through multiple hot spots. The 3D-PCN was synthesized on a paper substrate via direct one-step gold reduction, forming a coral-like nanoarchitecture with high absorption property for biofluids. This was fabricated as a urine test strip and then integrated with a handheld Raman system to develop an on-site urine diagnostic platform. The developed platform successfully classified the human prostate and pancreatic cancer urines in a label-free method supported by two types of deep learning networks, with high clinical sensitivity and specificity. Our technology has the potential to be utilized not only for urinary cancer diagnosis but also for various human biofluid sensing systems as a future point-of-care testing platform., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

A paper-based colourimetric assay for the detection of alanine transaminase has been developed. In the presence of alanine transaminase, 2,4-dinitrophenyl hydrazine changes to pyruvate hydrazone leading to a colour change from pale yellow to dark yellow. Reaction conditions were optimized using absorption spectroscopic studies. Hydrophobic patterns on the Whatman chromatographic paper were created by wax printing, and the reagents were drop cast at the reagent zone. On the paper device, the intensity of the yellow colour increases with ALT concentration in the range of 20-140 U/L in human serum. For the quantification of ALT, coloured images were captured using a digital camera and were processed with Image J software. The machine learning approach was also explored for the ALT analysis by training with colour images of the paper device and testing using a cross-validation procedure. The results obtained with real clinical samples on the paper device showed good accuracy of less than 5% relative error with the clinical lab results. Furthermore, the paper device shows high selectivity to ALT in the presence of various interfering species in blood serum with a sensitivity of 0.261 a.u/(U/L), a detection limit of 4.12 U/L, and precise results with an RSD of less than 7%. For the testing of whole blood, a plasma separation membrane was integrated with the patterned paper., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Abstract Purpose Paper-based artifacts hold significant cultural and social values. However, paper is intrinsically fragile to microorganisms, such as mold, due to its cellulose composition, which can serve as a microorganisms’ nutrient source. Mold not only can damage papers’ structural integrity and pose significant challenges to conservation works but also may subject individuals attending the contaminated artifacts to health risks. Current approaches for strain identification usually require extensive training, prolonged time for analysis, expensive operation costs, and higher risks of secondary damage due to sampling. Thus, in current conservation practices with mold-contaminated artifacts, little pre-screening or strain identification was performed before mold removal, and the cleaning techniques are usually broad-spectrum rather than strain-specific. With deep learning showing promising applications across various domains, this study investigated the feasibility of using a convolutional neural network (CNN) for fast in-situ recognition and classification of mold on paper. Methods Molds were first non-invasively sampled from ancient Xuan Paper-based Chinese books from the Qing and Ming dynasties. Strains were identified using molecular biology methods and the four most prevalent strains were inoculated on Xuan paper to create mockups for image collection. Microscopic images of the molds as well as their stains situated on paper were collected using a compound microscope and commercial microscope lens for cell phone cameras, which were then used for training CNN models with a transfer learning scheme to perform the classification of mold. To enable involvement and contribution from the research community, a web interface that actuates the process while providing interactive features for users to learn about the information of the classified strain was constructed. Moreover, a feedback functionality in the web interface was embedded for catching potential classification errors, adding additional training images, or introducing new strains, all to refine the generalizability and robustness of the model. Results & Conclusion In the study, we have constructed a suite of high-confidence classification CNN models for the diagnostic process for mold contamination in conservation. At the same time, a web interface was constructed that allows recurrently refining the model with human feedback through engaging the research community. Overall, the proposed framework opens new avenues for effective and timely identification of mold, thus enabling proactive and targeted mold remediation strategies in conservation.

There is increasing focus on applying deep learning methods to electrocardiograms (ECGs), with recent studies showing that neural networks (NNs) can predict future heart failure or atrial fibrillation from the ECG alone. However, large numbers of ECGs are needed to train NNs, and many ECGs are currently only in paper format, which are not suitable for NN training. We developed a fully-automated online ECG digitisation tool to convert scanned paper ECGs into digital signals. Using automated horizontal and vertical anchor point detection, the algorithm automatically segments the ECG image into separate images for the 12 leads and a dynamical morphological algorithm is then applied to extract the signal of interest. We then validated the performance of the algorithm on 515 digital ECGs, of which 45 were printed, scanned and redigitised. The automated digitisation tool achieved 99.0% correlation between the digitised signals and the ground truth ECG (n = 515 standard 3-by-4 ECGs) after excluding ECGs with overlap of lead signals. Without exclusion, the performance of average correlation was from 90 to 97% across the leads on all 3-by-4 ECGs. There was a 97% correlation for 12-by-1 and 3-by-1 ECG formats after excluding ECGs with overlap of lead signals. Without exclusion, the average correlation of some leads in 12-by-1 ECGs was 60-70% and the average correlation of 3-by-1 ECGs achieved 80-90%. ECGs that were printed, scanned, and redigitised, our tool achieved 96% correlation with the original signals. We have developed and validated a fully-automated, user-friendly, online ECG digitisation tool. Unlike other available tools, this does not require any manual segmentation of ECG signals. Our tool can facilitate the rapid and automated digitisation of large repositories of paper ECGs to allow them to be used for deep learning projects., (© 2022. The Author(s).)

Both the ABO and Rhesus (Rh) blood groups play crucial roles in blood transfusion medicine. Herein, we report a simple and low-cost paper-based analytical device (PAD) for phenotyping red blood cell (RBC) antigens. Using this Rh typing format, 5 Rh antigens on RBCs can be simultaneously detected and macroscopically visualized within 12 min. The proposed Rh phenotyping relies on the presence or absence of hemagglutination in the sample zones after immobilizing the antibodies targeting each Rh antigen. The PAD was optimized in terms of filter paper type, antibodies, and distance of the visualization zone. In this study, the optimal conditions were Whatman filter paper Grade 4; anti-D, -C, -E, -c, and -e antibodies; RBC suspension of 30%; and a visualization zone of 1 cm above the sample zone. The accuracy of simultaneously phenotyping the five Rh RBC antigens in the blood samples (n = 4692) was 99.19%, comparable with the accuracy of the gold-standard tube method used by blood bank laboratories in several regions of Thailand. Furthermore, decision making based on this method can be assisted by deep learning. After implementing a two-stage objective detection algorithm (YOLO v4-tiny) and classification model (DenseNet-201), the ambiguous images (n = 48) were interpreted with 100% accuracy. The PAD integrated with customized-region convolutional neural networks can reduce the interpretation discrepancies in RBC antigen phenotyping in any laboratory., (Copyright © 2022 Elsevier B.V. All rights reserved.)

One of the most popular and well-established forms of payment in use today is paper money. Handling paper money might be challenging for those with vision impairments. Assistive technology has been reinventing itself throughout time to better serve the elderly and disabled people. To detect paper currency and extract other useful information from them, image processing techniques and other advanced technologies, such as Artificial Intelligence, Deep Learning, etc., can be used. In this paper, we present a meticulously curated and comprehensive dataset named ‘NSTU-BDTAKA’ tailored for the simultaneous detection and recognition of a specific object of cultural significance - the Bangladeshi paper currency (in Bengali it is called ‘Taka’). This research aims to facilitate the development and evaluation of models for both taka detection and recognition tasks, offering a rich resource for researchers and practitioners alike. The dataset is divided into two distinct components: (i) taka detection, and (ii) taka recognition. The taka detection subset comprises 3,111 high-resolution images, each meticulously annotated with rectangular bounding boxes that encompass instances of the taka. These annotations serve as ground truth for training and validating object detection models, and we adopt the state-of-the-art YOLOv5 architecture for this purpose. In the taka recognition subset, the dataset has been extended to include a vast collection of 28,875 images, each showcasing various instances of the taka captured in diverse contexts and environments. The recognition dataset is designed to address the nuanced task of taka recognition providing researchers with a comprehensive set of images to train, validate, and test recognition models. This subset encompasses challenges such as variations in lighting, scale, orientation, and occlusion, further enhancing the robustness of developed recognition algorithms. The dataset NSTU-BDTAKA not only serves as a benchmark for taka detection and recognition but also fosters advancements in object detection and recognition methods that can be extrapolated to other cultural artifacts and objects. We envision that the dataset will catalyze research efforts in the field of computer vision, enabling the development of more accurate, robust, and efficient models for both detection and recognition tasks.

Electrocardiography (ECG) is essential in many heart diseases. However, some ECGs are recorded by paper, which can be highly noisy. Digitizing the paper-based ECG records into a high-quality signal is critical for further analysis. We formulated the digitization problem as a segmentation problem and proposed a deep learning method to digitize highly noisy ECG scans. Our method extracts the ECG signal in an end-to-end manner and can handle different paper record layouts. In the experiment, our model clearly extracted the ECG waveform with a Dice coefficient of 0.85 and accurately measured the common ECG parameters with more than 0.90 Pearson's correlation. We showed that the end-to-end approach with deep learning can be powerful in ECG digitization. To the best of our knowledge, we provide the first approach to digitize the least informative noisy binary ECG scans and potentially be generalized to digitize various ECG records., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)