Jason Ross Casar

All Publications

• Upconverting microgauges reveal intraluminal force dynamics in vivo. Nature Casar, J. R., McLellan, C. A., Shi, C., Stiber, A., Lay, A., Siefe, C., Parakh, A., Gaerlan, M., Gu, X. W., Goodman, M. B., Dionne, J. A. 2025; 637 (8044): 76-83

  Abstract

  The forces generated by action potentials in muscle cells shuttle blood, food and waste products throughout the luminal structures of the body. Although non-invasive electrophysiological techniques exist1-3, most mechanosensors cannot access luminal structures non-invasively4-6. Here we introduce non-toxic ingestible mechanosensors to enable the quantitative study of luminal forces and apply them to study feeding in living Caenorhabditis elegans roundworms. These optical 'microgauges' comprise upconverting NaY0.8Yb0.18Er0.02F4@NaYF4 nanoparticles embedded in polystyrene microspheres. Combining optical microscopy and atomic force microscopy to study microgauges in vitro, we show that force evokes a linear and hysteresis-free change in the ratio of emitted red to green light. With fluorescence imaging and non-invasive electrophysiology, we show that adult C. elegans generate bite forces during feeding on the order of 10 µN and that the temporal pattern of force generation is aligned with muscle activity in the feeding organ. Moreover, the bite force we measure corresponds to Hertzian contact stresses in the pressure range used to lyse the bacterial food of the worm7,8. Microgauges have the potential to enable quantitative studies that investigate how neuromuscular stresses are affected by ageing, genetic mutations and drug treatments in this organ and other luminal organs.

  View details for DOI 10.1038/s41586-024-08331-x

  View details for PubMedID 39743609

  View details for PubMedCentralID 3372093

• Engineering Bright and Mechanosensitive Alkaline-Earth Rare-Earth Upconverting Nanoparticles. The journal of physical chemistry letters McLellan, C. A., Siefe, C., Casar, J. R., Peng, C. S., Fischer, S., Lay, A., Parakh, A., Ke, F., Gu, X. W., Mao, W., Chu, S., Goodman, M. B., Dionne, J. A. 2022: 1547-1553

  Abstract

  Upconverting nanoparticles (UCNPs) are an emerging platform for mechanical force sensing at the nanometer scale. An outstanding challenge in realizing nanometer-scale mechano-sensitive UCNPs is maintaining a high mechanical force responsivity in conjunction with bright optical emission. This Letter reports mechano-sensing UCNPs based on the lanthanide dopants Yb3+ and Er3+, which exhibit a strong ratiometric change in emission spectra and bright emission under applied pressure. We synthesize and analyze the pressure response of five different types of nanoparticles, including cubic NaYF4 host nanoparticles and alkaline-earth host materials CaLuF, SrLuF, SrYbF, and BaLuF, all with lengths of 15 nm or less. By combining optical spectroscopy in a diamond anvil cell with single-particle brightness, we determine the noise equivalent sensitivity (GPa/√Hz) of these particles. The SrYb0.72Er0.28F@SrLuF particles exhibit an optimum noise equivalent sensitivity of 0.26 ± 0.04 GPa/√Hz. These particles present the possibility of robust nanometer-scale mechano-sensing.

  View details for DOI 10.1021/acs.jpclett.1c03841

  View details for PubMedID 35133831

• Lanthanide-Based Nanosensors: Refining Nanoparticle Responsiveness for Single Particle Imaging of Stimuli ACS PHOTONICS Casar, J. R., McLellan, C. A., Siefe, C., Dionne, J. A. 2021; 8 (1): 3–17

  View details for DOI 10.1021/acsphotonics.0c00894

  View details for Web of Science ID 000612567900002

• Lanthanide-Based Nanosensors: Refining Nanoparticle Responsiveness for Single Particle Imaging of Stimuli. ACS photonics Casar, J. R., McLellan, C. A., Siefe, C., Dionne, J. A. 2021; 8 (1): 3-17

  Abstract

  Lanthanide nanoparticles (LNPs) are promising sensors of chemical, mechanical, and temperature changes; they combine the narrow-spectral emission and long-lived excited states of individual lanthanide ions with the high spatial resolution and controlled energy transfer of nanocrystalline architectures. Despite considerable progress in optimizing LNP brightness and responsiveness for dynamic sensing, detection of stimuli with a spatial resolution approaching that of individual nanoparticles remains an outstanding challenge. Here, we highlight the existing capabilities and outstanding challenges of LNP sensors, en-route to nanometer-scale, single particle sensor resolution. First, we summarize LNP sensor read-outs, including changes in emission wavelength, lifetime, intensity, and spectral ratiometric values that arise from modified energy transfer networks within nanoparticles. Then, we describe the origins of LNP sensor imprecision, including sensitivity to competing conditions, interparticle heterogeneities, such as the concentration and distribution of dopant ions, and measurement noise. Motivated by these sources of signal variance, we describe synthesis characterization feedback loops to inform and improve sensor precision, and introduce noise-equivalent sensitivity as a figure of merit of LNP sensors. Finally, we project the magnitudes of chemical and pressure stimulus resolution achievable with single LNPs at nanoscale resolution. Our perspective provides a roadmap for translating ensemble LNP sensing capabilities to the single particle level, enabling nanometer-scale sensing in biology, medicine, and sustainability.

  View details for DOI 10.1021/acsphotonics.0c00894

  View details for PubMedID 34307765

  View details for PubMedCentralID PMC8297747

• Alkaline-earth Rare-earth Upconverting Nanoparticles as Bio-compatible Mechanical Force Sensors McLellan, C. A., Siefe, C. P., Fischer, S., Casar, J. R., Swearer, D. F., Goodman, M. B., Dionne, J. A., IEEE IEEE. 2020

  View details for Web of Science ID 000612090003343