About

Eric Darling is an Associate Professor of Medical Science, Orthopaedics, and Engineering at Brown University. His research involves developing new approaches to measuring cell elasticity, which is an emerging factor in human health. Darling's work has contributed to making the measurement of cell squishiness and stiffness faster, easier, and more reliable, in collaboration with the National Institute of Standards and Technology. His research efforts are recognized as impactful within the biomedical and engineering fields, and he is actively involved in advancing understanding of cellular mechanics.

Research topics

• Cell biology
• Biology
• Chemistry
• Materials science
• Nanotechnology

Selected publications

• Estimating single-cell elastic modulus in a serial microfluidic cytometer from time-of-flight and fluorescence signals analysis

  Lab on a Chip · 2026-01-01

  articleOpen accessCorresponding

  Cellular state, function, and disease all contribute to whole-cell mechanical properties. Investigating these relationships is often difficult due to low measurement throughput, inability to draw one-to-one connections between mechanical and biochemical properties, and significant or unknown measurement uncertainty. To address these needs, we demonstrate that a serial microfluidic cytometer can realize high-throughput estimates of elastic modulus and size from fluorescence signals and time-of-flight (TOF) measurements of cell-like particles in flow. To analyze the resulting data, we leverage a combined spectral time-series analysis (STA) of fluorescence measurements and a mechanics-based Gaussian-process regression model. Critically, the former yields independent estimates of the particle size, whereas the latter characterizes the relationship between size, elasticity, and TOF, thereby allowing us to decouple such effects and extract estimates of elastic modulus. We calibrate the model using cell-like polyacrylamide microparticles with a range of known sizes (8.9 μm to 23 μm diameter) and stiffnesses (0.1 kPa to 9.1 kPa). The calibrated model is then applied to estimate the per-particle size and elastic modulus of live MG-63 osteosarcoma cells. Cell viability through the device was high (>90%), and the median diameter of 16.3 μm and elastic modulus of 0.9 kPa for MG-63s were consistent with light microscopy and AFM measurements. Thus, our novel device and model have the potential to expand mechanophenotyping capabilities by enabling high-throughput, single-cell measurements with uncertainty quantification. Furthermore, this emerging flow cytometry technique is directly compatible with fluorescence measurements of biochemical composition.

  PublisherOA PDFDOI

• Identifying Immunomodulatory Subpopulations of Adipose Stromal Vascular Fraction and Stem/Stromal Cells Through Single-Cell Transcriptomics and Bulk Proteomics

  Stem Cell Reviews and Reports · 2025-05-14 · 2 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Selection of Force Sensors for <i>In Situ</i> Measurement of Neotissue Microenvironments

  Tissue Engineering Part A · 2024-10-25 · 2 citations

  articleOpen accessSenior author

  Mechanical forces are a critical stimulus in both native and engineered tissues. Direct measurement of these microenvironmental forces has been challenging, particularly for cell-dense models. To address this, we previously developed hydrogel-based force sensors that are approximately the size of a cell and can be imaged over time to computationally assess the forces exerted by surrounding cells and matrix. The goal of this project was to identify how the physical characteristics of force sensors impact measurements. Sensors were varied in size, elastic modulus, and surface coating before being included in stem cell suspensions that then spontaneously self-assembled into spheroidal neotissues. Using this model of early mesenchymal condensation, we hypothesized that larger, softer sensors would provide greater sensitivity and precision, whereas protein coatings would influence the directionality of applied forces (tensile vs. compressive). These experiments were conducted using a high-content imaging system that allowed analysis of over a thousand sensors to evaluate the various conditions. Results indicated that measurement fidelity was highest for force sensors that had a diameter &gt;20 µm and modulus ∼0.2 kPa. Extremely soft sensors deformed too much, whereas stiffer sensors deformed too little. Collagen and N-cadherin coatings, which replicated cell–matrix or cell–cell binding, respectively, allowed for tensile forces to be exerted on the sensors, with greater forces being observed for N-cadherin sensors in these highly cellular neotissue constructs. Uncoated sensors were universally compressed due to the lack of cell–sensor adhesion. Disruption of the actin cytoskeleton lessened microenvironmental forces, whereas disruption of microtubules had no measurable effect. Potential future applications of the technology include studies of in situ forces in developing tissues as well as a real-time sensor for monitoring the growth of engineered constructs.

  PublisherOA PDFDOI

• Microparticles with tunable, cell-like properties for quantitative acoustic mechanophenotyping

  Microsystems & Nanoengineering · 2023-07-12 · 7 citations

  articleOpen access

  Mechanical properties of biological cells have been shown to correlate with their biomolecular state and function, and therefore methods to measure these properties at scale are of interest. Emerging microfluidic technologies can measure the mechanical properties of cells at rates over 20,000 cells/s, which is more than four orders of magnitude faster than conventional instrumentation. However, precise and repeatable means to calibrate and test these new tools remain lacking, since cells themselves are by nature variable. Commonly, microfluidic tools use rigid polymer microspheres for calibration because they are widely available in cell-similar sizes, but conventional microspheres do not fully capture the physiological range of other mechanical properties that are equally important to device function (e.g., elastic modulus and density). Here, we present for the first time development of monodisperse polyacrylamide microparticles with both tunable elasticity and tunable density. Using these size, elasticity, and density tunable particles, we characterized a custom acoustic microfluidic device that makes single-cell measurements of mechanical properties. We then applied the approach to measure the distribution of the acoustic properties within samples of human leukocytes and showed that the system successfully discriminates lymphocytes from other leukocytes. This initial demonstration shows how the tunable microparticles with properties within the physiologically relevant range can be used in conjunction with microfluidic devices for efficient high-throughput measurements of mechanical properties at single-cell resolution.

  PublisherOA PDFDOI

• Datasets generated from the study on trace lead removal by inactive yeast cells

  Figshare · 2022-01-01

  datasetOpen access

  Datasets generated and analyzed during the Pb biosorption study, including yeast growth curve, HPLC data from yeast washing, ICP-MS data for adsorption isotherm, kinetics, chitin, and pH experiments, as well as data from the XPS and FTIR analyses.

  PublisherDOI

• Discovery of surface biomarkers for cell mechanophenotype via an intracellular protein-based enrichment strategy

  Cellular and Molecular Life Sciences · 2022-05-27 · 6 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Chondrogenesis of Adipose-Derived Stem Cells Using an Arrayed Spheroid Format

  Cellular and Molecular Bioengineering · 2022-10-22 · 2 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Cell-like microparticles with tunable acoustic properties for calibrating devices

  The Journal of the Acoustical Society of America · 2022-10-01

  article

  Mechanophenotype of biological cells has demonstrated correlation with biomolecular states and cell function. Hence, new methods to measure mechanophenotype at high throughput are of growing interest. Acoustophoretic microdevices can characterize cell mechanical features; however, calibration particles with physiologically relevant properties are needed to quantify and optimize device performance. Currently, conventional polymer microspheres are rigid and do not replicate cell deformation and compressibility. To address this, we developed monodisperse, tunable, cell-like microparticles (MPs) from polyacrylamide hydrogel, fabricated with a microfluidic droplet generator. Size and compressibility are adjusted by fabrication parameters, and density is adjusted by incorporation of nanoparticles (NPs). Here, we present for the first time microparticles of reduced density and acoustic contrast (lower than unloaded MPs) achieved by loading MPs with nanoparticles of low molecular weight alkanes. We produced the NPs by sonication and photopolymerization before addition to the MP precursor. NP-loaded MPs were less dense than unloaded MPs at 1005.9 and 1013.6kg/m3, respectively, and they exhibited negative acoustic contrast by acoustophoresis in aqueous medium while that of unloaded MPs was positive. These new particles extend the tunable range of acoustic contrast, mimicking and exceeding that of most biological cells and could also aid cell separation when conjugated to cells.

  PublisherDOI

• Lead removal at trace concentrations from water by inactive yeast cells

  Communications Earth & Environment · 2022-06-13 · 24 citations

  articleOpen access

  Abstract Traces of heavy metals found in water resources, due to mining activities and e-waste discharge, pose a global threat. Conventional treatment processes fail to remove toxic heavy metals, such as lead, from drinking water in a resource-efficient manner when their initial concentrations are low. Here, we show that by using the yeast Saccharomyces cerevisiae we can effectively remove trace lead from water via a rapid mass transfer process, called biosorption, achieving an uptake of up to 12 mg lead per gram of biomass in solutions with initial lead concentrations below 1 part per million. Through spectroscopic analyses, we found that the yeast cell wall plays a crucial role in this process, with its mannoproteins and β-glucans being the key potential lead adsorbents. Furthermore, by employing nanomechanical characterization in the yeast biomass, we discovered that biosorption is linked to an increase in cell wall stiffness. These findings open new opportunities for using environmentally friendly and abundant biomaterials for advanced water treatment targeting emerging contaminants.

  PublisherOA PDFDOI

• Physiologically relevant microparticles with mechanically tunable properties for acoustophoretic and microfluidic device calibration

  Proceedings of meetings on acoustics · 2022-01-01

  article
  PublisherDOI

Recent grants

• NIH Grant R00AR054673

  NIH · $829k · 2012

• NIH Grant F32AR053448

  NIH · $49k · 2007

• NIH Grant K99AR054673

  NIH · $81k · 2009

• High-yield, lineage-specific enrichment of living mesenchymal stem cells

  NIH · $1.8M · 2013–2019

• CAREER: Mechanical Biomarkers and Mesenchymal Stem Cell Differentiation

  NSF · $438k · 2013–2018

Frequent coauthors

• Vera C. Fonseca

  Brown University

  39 shared

• Farshid Guilak

  Shriners Hospitals for Children - St. Louis

  34 shared

• Nicholas R. Labriola

  Brown University

  31 shared

• Kyriacos A. Athanasiou

  University of California, Irvine

  27 shared

• Stefan Zauscher

  Pratt Institute

  25 shared

• Jessica S. Sadick

  22 shared

• Ryan Dubay

  Brown University

  21 shared

• Edith Mathiowitz

  18 shared

Education

• Post-doctoral fellow, Orthopaedic Surgery

  Duke University

  2009

• Ph.D., Bioengineering

  Rice University

  2005

• B.S., Engineering

  Harvey Mudd College

  2000