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Dino Di Carlo

Publications and source records attributed to Dino Di Carlo.

17 recordsLinked to original sources

BioEVAL: A global, multi-institutional benchmark of large language and multimodal models for bioengineering

Large Language Models (LLMs) have demonstrated historic breakthroughs in general reasoning with early successes in biomedical science. However, existing LLM benchmarking emphasizes factual recall, offering limited insight into model performance on frontier and multimodal tasks. We assembled BioEVAL (BioEngineering Validation of AI and LLMs), a global, multi-institutional initiative designed to assess experimental reasoning capability across bioengineering (BE) subfields. BioEVAL spans 11 major BE subfields plus a set of uncategorized items, bringing together 22 research groups to create a PhD-level benchmark comprising 608 evaluation items: 1) 380 multiple-choice questions (MCQs, 359 retained after audit), 2) 218 literature synthesis tasks, and 3) 10 multimodal problems with experimental image interpretation. Benchmark items underwent authoring-group expert review and centralized quality control before evaluation. Following evaluation, a blinded cross-group consensus audit of the highest- and lowest-accuracy MCQ items flagged 21 questions for revision or removal; these were withheld, and all reported MCQ results are computed on the 359 retained items. We evaluated diverse cloud-scale foundation/multimodal models (e.g., ChatGPT, Gemini, and Grok) and locally deployable models suitable for inference on consumer-grade GPUs. Models achieved the highest accuracy of up to 90% on MCQs, similarity score of 0.72 on literature synthesis, and accuracy of 80% on a small sample of multimodal reasoning questions, with substantial performance variation across subfields. Leaderboard rankings characterize current capabilities, limitations, and development priorities across the evaluated BE task categories. BioEVAL is maintained as an extensible benchmark with standardized protocols for continuing expert item contribution and model evaluation.

cs.AI↗

Whole Blood-Based Point-of-Care Assay for Single-Tier Lyme Disease Testing

Rapid point-of-care diagnostics that operate directly on whole blood can accelerate clinical decision-making by bypassing complex sample preprocessing and centralized laboratory infrastructure. However, most serologic assays still require serum or plasma, limiting near-patient deployment. This challenge is particularly evident for Lyme disease, whose diagnosis relies on centralized two-tier serology. Here, we present a whole-blood multiplexed vertical flow assay (WB-xVFA) that performs single-tier Lyme serology directly from 50 microliter of whole blood. The assay combines multilayer blood filtration with a peptide-patterned nitrocellulose membrane to separate cellular components and detect Lyme-associated IgM/IgG responses on a cartridge. Coupled with smartphone-based imaging and machine-learning analysis, the WB-xVFA provides results in 20 min. The assay remained robust across hematocrits up to 60% and sample volumes ranging from 25 to 100 microliter. In blinded testing of 62 whole-blood measurements, it achieved ~97% sensitivity and specificity, demonstrating the feasibility of rapid, near-patient whole-blood Lyme serology.

physics.med-ph↗

Interfacial Potential Transduction for Diagnostics

A major barrier to decentralized, near-patient diagnostics is the lack of a signal transduction modality that is both analytically precise and accessible at the point of care. Optical readouts remain instrument-dependent and difficult to miniaturize, while compact electrochemical readouts are prone to matrix-derived signal distortion, limiting their biomarker coverage in real clinical settings. Here, we define interfacial potential transduction as a standardized electrical modality for portable, clinical-grade diagnostics across diverse assay formats. A mechanistic framework identifying key sample matrix parameters within the interfacial potentials transduction system enables control of biofluid-derived interference, and is demonstrated in a widely accessible lateral flow immunoassay format through quantitative detection of estradiol, progesterone, and luteinizing hormone in human plasma with high correlation (r2 > 0.97) to clinical analyzers. Broader applicability across representative diagnostic sectors is further demonstrated through exceptional performance including glucose quantification for biochemical analysis with limit of detection (LOD) of 0.92 ug/dL, HIV p24 capsid protein under an immunomagnetic separation workflow (LOD = 44.8 fg/mL), and hepatitis B virus detection within 5 min via loop-mediated isothermal amplification for molecular diagnostics. Together, these results establish interfacial potentials transduction as a unified diagnostic paradigm for near-patient deployment beyond optical and electrochemical approaches.

q-bio.BM↗

Autonomous Uncertainty Quantification for Computational Point-of-care Sensors

Computational point-of-care (POC) sensors enable rapid, low-cost, and accessible diagnostics in emergency, remote and resource-limited areas that lack access to centralized medical facilities. These systems can utilize neural network-based algorithms to accurately infer a diagnosis from the signals generated by rapid diagnostic tests or sensors. However, neural network-based diagnostic models are subject to hallucinations and can produce erroneous predictions, posing a risk of misdiagnosis and inaccurate clinical decisions. To address this challenge, here we present an autonomous uncertainty quantification technique developed for POC diagnostics. As our testbed, we used a paper-based, computational vertical flow assay (xVFA) platform developed for rapid POC diagnosis of Lyme disease, the most prevalent tick-borne disease globally. The xVFA platform integrates a disposable paper-based assay, a handheld optical reader and a neural network-based inference algorithm, providing rapid and cost-effective Lyme disease diagnostics in under 20 min using only 20 uL of patient serum. By incorporating a Monte Carlo dropout (MCDO)-based uncertainty quantification approach into the diagnostics pipeline, we identified and excluded erroneous predictions with high uncertainty, significantly improving the sensitivity and reliability of the xVFA in an autonomous manner, without access to the ground truth diagnostic information of patients. Blinded testing using new patient samples demonstrated an increase in diagnostic sensitivity from 88.2% to 95.7%, indicating the effectiveness of MCDO-based uncertainty quantification in enhancing the robustness of neural network-driven computational POC sensing systems.

physics.med-ph↗

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↗

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↗

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↗

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↗

Fluid dynamics alters liquid-liquid phase separation in confined aqueous two-phase systems

Liquid-liquid phase separation is key to understanding aqueous two-phase systems (ATPS) arising throughout cell biology, medical science, and the pharmaceutical industry. Controlling the detailed morphology of phase-separating compound droplets leads to new technologies for efficient single-cell analysis, targeted drug delivery, and effective cell scaffolds for wound healing. We present a computational model of liquid-liquid phase separation relevant to recent laboratory experiments with gelatin-polyethylene glycol mixtures. We include buoyancy and surface-tension-driven finite viscosity fluid dynamics with thermally induced phase separation. We show that the fluid dynamics greatly alters the evolution and equilibria of the phase separation problem. Notably, buoyancy plays a critical role in driving the ATPS to energy-minimizing crescent-shaped morphologies and shear flows can generate a tenfold speedup in particle formation. Neglecting fluid dynamics produces incorrect minimum-energy droplet shapes. The model allows for optimization of current manufacturing procedures for structured microparticles and improves understanding of ATPS evolution in confined and flowing settings important in biology and biotechnology.

cond-mat.soft↗

Deep learning-enabled multiplexed point-of-care sensor using a paper-based fluorescence vertical flow assay

We demonstrate multiplexed computational sensing with a point-of-care serodiagnosis assay to simultaneously quantify three biomarkers of acute cardiac injury. 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 microliters 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 (CK-MB) and heart-type fatty acid binding protein (FABP), achieving less than 0.52 ng/mL 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 showed 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 make it a promising point-of-care sensor platform that could expand access to diagnostics in resource-limited settings.

physics.med-ph↗

The Evolution of Flow and Mass Transport in 3D Confined Cavities

Flow in channels and ducts with adjoining cavities are common in natural and engineered systems. Here we report numerical and experimental results of 3D confined cavity flow, identifying critical conditions in the recirculating flow formation and mass transport over a range of channel flow properties ($0.1\leq Re \leq 300$) and cavity aspect ratio ($0.1 \leq H/X_{s} \leq1$). In contrast to 2D systems, a mass flux boundary is not formed in 3D confined cavity-channel flow. Streamlines directly enter a recirculating vortex in the cavity and exit to the main channel leading to an exponential increase in the cavity mass flux when the recirculating vortex fills the cavity volume. These findings extend our understanding of flow entry and exit in cavities and suggest conditions where convective mass transport into and out of cavities would be amplified and vortex particle capture reduced.

physics.flu-dyn↗

An Automated, Cost-Effective Optical System for Accelerated Anti-microbial Susceptibility Testing (AST) using Deep Learning

Antimicrobial susceptibility testing (AST) is a standard clinical procedure used to quantify antimicrobial resistance (AMR). Currently, the gold standard method requires incubation for 18-24 h and subsequent inspection for growth by a trained medical technologist. We demonstrate an automated, cost-effective optical system that delivers early AST results, minimizing incubation time and eliminating human errors, while remaining compatible with standard phenotypic assay workflow. The system is composed of cost-effective components and eliminates the need for optomechanical scanning. A neural network processes the captured optical intensity information from an array of fiber optic cables to determine whether bacterial growth has occurred in each well of a 96-well microplate. When the system was blindly tested on isolates from 33 patients with Staphylococcus aureus infections, 95.03% of all the wells containing growth were correctly identified using our neural network, with an average of 5.72 h of incubation time required to identify growth. 90% of all wells (growth and no-growth) were correctly classified after 7 h, and 95% after 10.5 h. Our deep learning-based optical system met the FDA-defined criteria for essential and categorical agreements for all 14 antibiotics tested after an average of 6.13 h and 6.98 h, respectively. Furthermore, our system met the FDA criteria for major and very major error rates for 11 of 12 possible drugs after an average of 4.02 h, and 9 of 13 possible drugs after an average of 9.39 h, respectively. This system could enable faster, inexpensive, automated AST, especially in resource limited settings, helping to mitigate the rise of global AMR.

q-bio.QM↗

Shape-design for stabilizing micro-particles in inertial microfluidic flows

Design of microparticles which stabilize at the centerline of a channel flow when part of a dilute suspension is examined numerically for moderate Reynolds numbers ($10 \le Re \le 80$). Stability metrics for particles with arbitrary shapes are formulated based on linear-stability theory. Particle shape is parametrized by a compact, Non-Uniform Rational B-Spline (NURBS)-based representation. Shape-design is posed as an optimization problem and solved using adaptive Bayesian optimization. We focus on designing particles for maximal stability at the channel-centerline robust to perturbations. Our results indicate that centerline-focusing particles are families of characteristic "fish"/"bottle"/"dumbbell"-like shapes, exhibiting fore-aft asymmetry. A parametric exploration is then performed to identify stable particle-designs at different k's (particle chord-to-channel width ratio) and Re's ($0.1 \le k \le 0.4, 10 \le Re \le 80$). Particles at high-k's and Re's are highly stabilized when compared to those at low-k's and Re's. A comparison of the modified dumbbell designs from the current framework also shows better performance to perturbations in Fluid-Structure Interaction (FSI) when compared to the rod-disk model reported previously (Uspal & Doyle 2014) for low-Re Hele-Shaw flow. We identify basins of attraction around the centerline, which span larger release-angle-ranges and lateral locations (tending to the channel width) for narrower channels, which effectively standardizes the notion of global focusing in such configurations using the current stability-paradigm. The present framework is illustrated for 2D cases and is potentially generalizable to stability in 3D flow-fields. The current formulation is also agnostic to Re and particle/channel geometry which indicates substantial potential for integration with imaging flow-cytometry tools and microfluidic biosensing-assays.

physics.flu-dyn↗

Direct Measurement of Particle Inertial Migration in Rectangular Microchannels

Particles traveling at high velocities through microfluidic channels migrate from their starting streamlines due to inertial lift forces. Theories predict different scaling laws for these forces and there is little experimental evidence by which to validate theory. Here we experimentally measure the three dimensional positions and migration velocities of particles. Our experimental method relies on a combination of sub-pixel accurate particle tracking and velocimetric reconstruction of the depth dimension to track thousands of individual particles in three dimensions. We show that there is no simple scaling of inertial forces upon particle size, but that migration velocities agree well with numerical simulations and with a two-term asymptotic theory that contains no unmeasured parameters.

physics.flu-dyn↗

Optimization of micropillar sequences for fluid flow sculpting

Inertial fluid flow deformation around pillars in a microchannel is a new method for controlling fluid flow. Sequences of pillars have been shown to produce a rich phase space with a wide variety of flow transformations. Previous work has successfully demonstrated manual design of pillar sequences to achieve desired transformations of the flow cross-section, with experimental validation. However, such a method is not ideal for seeking out complex sculpted shapes as the search space quickly becomes too large for efficient manual discovery. We explore fast, automated optimization methods to solve this problem. We formulate the inertial flow physics in microchannels with different micropillar configurations as a set of state transition matrix operations. These state transition matrices are constructed from experimentally validated streamtraces. This facilitates modeling the effect of a sequence of micropillars as nested matrix-matrix products, which have very efficient numerical implementations. With this new forward model, arbitrary micropillar sequences can be rapidly simulated with various inlet configurations, allowing optimization routines quick access to a large search space. We integrate this framework with the genetic algorithm and showcase its applicability by designing micropillar sequences for various useful transformations. We computationally discover micropillar sequences for complex transformations that are substantially shorter than manually designed sequences. We also determine sequences for novel transformations that were difficult to manually design. Finally, we experimentally validate these computational designs by fabricating devices and comparing predictions with the results from confocal microscopy.

physics.flu-dyn↗

Lateral migration of living cells in inertial microfluidic systems explored by fully three-dimensional numerical simulation

The effects of cell size and deformability on the lateral migration and deformation of living cells flowing through a rectangular microchannel has been numerically investigated and compared with the inertial-microfluidics data on detection and separation of cells. The results of this work indicate that the cells move closer to the centerline if they are bigger and/or more deformable and that their equilibrium position is largely determined by the solvent (cytosol) viscosity, which is much less than the polymer (cytoskeleton) viscosity measured in most rheological systems. Simulations also suggest that decreasing channel dimensions leads to larger differences in equilibrium position for particles of different viscoelastic properties, giving design guidance for the next generation of microfluidic cell separation chips.

physics.flu-dyn↗

Inertially-induced secondary flow in microchannels

We report a novel technique to passively create strong secondary flows at moderate to high flow rates in microchannels, accurately control them and finally, due to their deterministic nature, program them into microfluidic platforms. Based on the flow conditions and due to the presence of the pillars in the channel, the flow streamlines will lose their fore-aft symmetry. As a result of this broken symmetry the fluid is pushed away from the pillar at the center of the channel (i.e. central z-plane). As the flow needs to maintain conservation of mass, the fluid will laterally travel in the opposite direction near the top and bottom walls. Therefore, a NET secondary flow will be created in the channel cross-section which is depicted in this video. The main platform is a simple straight channel with posts (i.e. cylindrical pillars - although other pillar cross-sections should also function) placed along the channel. Channel measures were 200 \mum\times50 \mum, with pillars of 100 \mum in diameter. Positioning the pillars in different locations within the cross-section of the channel will result in induction of different secondary flow patterns, which can be carefully engineered. The longitudinal spacing of the pillars is another design parameter (600 \mum spacing was used for this video). The device works over a wide range (moderate to high) flow rates. We used 150 \muL/min in this experiment. The device has 3 inlets where a dye stream is co-flowed between two water streams. In this video, one can see the effect of the net secondary flow created by inertia in the microchannel by visualizing the cross-section of the fluorescently labeled stream. Confocal images are sequentially taken at the inlet and after 49 consecutive pillars.

physics.flu-dyn↗