arXiv subjects

Merve Eryilmaz

Publications and source records attributed to Merve Eryilmaz.

7 recordsLinked to original sources

arXiv2026

Continuous quantification of viral plaque dynamics using ultra-large-area label-free imaging enables rapid antiviral susceptibility testing

The plaque reduction assay (PRA) remains the gold standard for antiviral susceptibility testing, evaluating drug potency by measuring reductions in plaque-forming units (PFUs). However, the traditional PRA is time-consuming, labor-intensive, prone to manual counting errors, and offers limited scalability. Moreover, its reliance on destructive fixation and chemical staining reduces the assay to a static, endpoint observation, obscuring the dynamic, time-resolved kinetics of dose-dependent viral inhibition. Here, we introduce a label-free, time-resolved PRA platform that transforms the conventional assay into a continuous, high-dimensional measurement of viral infection dynamics. Our system integrates a compact lens-free imaging setup with a custom-designed ultra-large-area (100 cm^2) thin-film transistor (TFT) image sensor and deep learning-based algorithms to autonomously quantify PFU dynamics within an incubator. Validated using herpes simplex virus type-1 (HSV-1) treated with acyclovir, the platform matched chemically-stained ground truth measurements with zero false positives while accelerating readout by ~26 hours. Crucially, our system revealed that increasing drug concentrations induce temporally distinct delays and suppress new PFU formation, enabling conclusive drug efficacy evaluations within ~60 hours post-infection. This scalable, label-free framework redefines antiviral susceptibility testing as a rapid, time-resolved and information-rich measurement framework, providing a generalizable platform for virology research, high-throughput drug screening, and clinical diagnostics.

physics.app-ph↗

arXiv2025

Deep learning-enhanced dual-mode multiplexed optical sensor for point-of-care diagnostics of cardiovascular diseases

Rapid and accessible cardiac biomarker testing is essential for the timely diagnosis and risk assessment of myocardial infarction (MI) and heart failure (HF), two interrelated conditions that frequently coexist and drive recurrent hospitalizations with high mortality. However, current laboratory and point-of-care testing systems are limited by long turnaround times, narrow dynamic ranges for the tested biomarkers, and single-analyte formats that fail to capture the complexity of cardiovascular disease. Here, we present a deep learning-enhanced dual-mode multiplexed vertical flow assay (xVFA) with a portable optical reader and a neural network-based quantification pipeline. This optical sensor integrates colorimetric and chemiluminescent detection within a single paper-based cartridge to complementarily cover a large dynamic range (spanning ~6 orders of magnitude) for both low- and high-abundance biomarkers, while maintaining quantitative accuracy. Using 50 uL of serum, the optical sensor simultaneously quantifies cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) within 23 min. The xVFA achieves sub-pg/mL sensitivity for cTnI and sub-ng/mL sensitivity for CK-MB and NT-proBNP, spanning the clinically relevant ranges for these biomarkers. Neural network models trained and blindly tested on 92 patient serum samples yielded a robust quantification performance (Pearson's r > 0.96 vs. reference assays). By combining high sensitivity, multiplexing, and automation in a compact and cost-effective optical sensor format, the dual-mode xVFA enables rapid and quantitative cardiovascular diagnostics at the point of care.

physics.med-ph↗

arXiv2024

Deep learning-enhanced chemiluminescence vertical flow assay for high-sensitivity cardiac troponin I testing

Democratizing biomarker testing at the point-of-care requires innovations that match laboratory-grade sensitivity and precision in an accessible format. Here, we demonstrate high-sensitivity detection of cardiac troponin I (cTnI) through innovations in chemiluminescence-based sensing, imaging, and deep learning-driven analysis. This chemiluminescence vertical flow assay (CL-VFA) enables rapid, low-cost, and precise quantification of cTnI, a key cardiac protein for assessing heart muscle damage and myocardial infarction. The CL-VFA integrates a user-friendly chemiluminescent paper-based sensor, a polymerized enzyme-based conjugate, a portable high-performance CL reader, and a neural network-based cTnI concentration inference algorithm. The CL-VFA measures cTnI over a broad dynamic range covering six orders of magnitude and operates with 50 uL of serum per test, delivering results in 25 min. This system achieves a detection limit of 0.16 pg/mL with an average coefficient of variation under 15%, surpassing traditional benchtop analyzers in sensitivity by an order of magnitude. In blinded validation, the computational CL-VFA accurately measured cTnI concentrations in patient samples, demonstrating a robust correlation against a clinical-grade FDA-cleared analyzer. These results highlight the potential of CL-VFA as a robust diagnostic tool for accessible, rapid cardiac biomarker testing that meets the needs of diverse healthcare settings, from emergency care to underserved regions.

physics.med-ph↗

arXiv2024

Virtual Gram staining of label-free bacteria using darkfield microscopy and deep learning

Gram staining has been one of the most frequently used staining protocols in microbiology for over a century, utilized across various fields, including diagnostics, food safety, and environmental monitoring. Its manual procedures make it vulnerable to staining errors and artifacts due to, e.g., operator inexperience and chemical variations. Here, we introduce virtual Gram staining of label-free bacteria using a trained deep neural network that digitally transforms darkfield images of unstained bacteria into their Gram-stained equivalents matching brightfield image contrast. After a one-time training effort, the virtual Gram staining model processes an axial stack of darkfield microscopy images of label-free bacteria (never seen before) to rapidly generate Gram staining, bypassing several chemical steps involved in the conventional staining process. We demonstrated the success of the virtual Gram staining workflow on label-free bacteria samples containing Escherichia coli and Listeria innocua by quantifying the staining accuracy of the virtual Gram staining model and comparing the chromatic and morphological features of the virtually stained bacteria against their chemically stained counterparts. This virtual bacteria staining framework effectively bypasses the traditional Gram staining protocol and its challenges, including stain standardization, operator errors, and sensitivity to chemical variations.

q-bio.QM↗

arXiv2024

A paper-based multiplexed serological test to monitor immunity against SARS-CoV-2 using machine learning

The rapid spread of SARS-CoV-2 caused the COVID-19 pandemic and accelerated vaccine development to prevent the spread of the virus and control the disease. Given the sustained high infectivity and evolution of SARS-CoV-2, there is an ongoing interest in developing COVID-19 serology tests to monitor population-level immunity. To address this critical need, we designed a paper-based multiplexed vertical flow assay (xVFA) using five structural proteins of SARS-CoV-2, detecting IgG and IgM antibodies to monitor changes in COVID-19 immunity levels. Our platform not only tracked longitudinal immunity levels but also categorized COVID-19 immunity into three groups: protected, unprotected, and infected, based on the levels of IgG and IgM antibodies. We operated two xVFAs in parallel to detect IgG and IgM antibodies using a total of 40 uL of human serum sample in <20 min per test. After the assay, images of the paper-based sensor panel were captured using a mobile phone-based custom-designed optical reader and then processed by a neural network-based serodiagnostic algorithm. The trained serodiagnostic algorithm was blindly tested with serum samples collected before and after vaccination or infection, achieving an accuracy of 89.5%. The competitive performance of the xVFA, along with its portability, cost-effectiveness, and rapid operation, makes it a promising computational point-of-care (POC) serology test for monitoring COVID-19 immunity, aiding in timely decisions on the administration of booster vaccines and general public health policies to protect vulnerable populations.

physics.med-ph↗

arXiv2024

Deep learning-enhanced paper-based vertical flow assay for high-sensitivity troponin detection using nanoparticle amplification

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 uL 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 six 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.

physics.med-ph↗

arXiv2023

Rapid and stain-free quantification of viral plaque via lens-free holography and deep learning

We present a rapid and stain-free quantitative viral plaque assay using lensfree holographic imaging and deep learning. This cost-effective, compact, and automated device significantly reduces the incubation time needed for traditional plaque assays while preserving their advantages over other virus quantification methods. This device captures ~0.32 Giga-pixel/hour phase information of the objects per test well, covering an area of ~30x30 mm^2, in a label-free manner, eliminating staining entirely. We demonstrated the success of this computational method using vesicular stomatitis virus (VSV), herpes simplex virus (HSV-1) and encephalomyocarditis virus (EMCV). Using a neural network, this stain-free device automatically detected the first cell lysing events due to the VSV viral replication as early as 5 hours after the incubation, and achieved >90% detection rate for the VSV plaque-forming units (PFUs) with 100% specificity in <20 hours, providing major time savings compared to the traditional plaque assays that take at least 48 hours. Similarly, this stain-free device reduced the needed incubation time by ~48 hours for HSV-1 and ~20 hours for EMCV, achieving >90% detection rate with 100% specificity. We also demonstrated that this data-driven plaque assay offers the capability of quantifying the infected area of the cell monolayer, performing automated counting and quantification of PFUs and virus-infected areas over a 10-fold larger dynamic range of virus concentration than standard viral plaque assays. This compact, low-cost, automated PFU quantification device can be broadly used in virology research, vaccine development, and clinical applications.

physics.ins-det↗