Ethan Li

All Publications

• ESPressoscope: A small and powerful approach for in situ microscopy. PloS one Li, E., Saggiomo, V., Ouyang, W., Prakash, M., Diederich, B. 2024; 19 (10): e0306654

  Abstract

  Microscopy is essential for detecting, identifying, analyzing, and measuring small objects. Access to modern microscopy equipment is crucial for scientific research, especially in the biomedical and analytical sciences. However, the high cost of equipment, limited availability of parts, and challenges associated with transporting equipment often limit the accessibility and operational capabilities of these tools, particularly in field sites and other remote or resource-limited settings. Thus, there is a need for affordable and accessible alternatives to traditional microscopy systems. We address this challenge by investigating the feasibility of using a simple microcontroller board not only as a portable and field-ready digital microscope, but furthermore as a versatile platform which can easily be adapted to a variety of imaging applications. By adding a few external components, we demonstrate that a low-cost ESP32 camera board can be used to build an autonomous in situ platform for digital time-lapse imaging of cells. Our prototype of this approach, which we call ESPressoscope, can be adapted to applications ranging from monitoring incubator cell cultures in the lab to observing ecological phenomena in the sea, and it can be adapted for other techniques such as microfluidics or spectrophotometry. Our prototype of the ESPressoscope concept achieves a low power consumption and small size, which makes it ideal for field research in environments and applications where microscopy was previously infeasible. Its Wi-Fi connectivity enables integration with external image processing and storage systems, including on cloud platforms when internet access is available. Finally, we present several web browser-based tools to help users operate and manage our prototype's software. Our findings demonstrate the potential for low-cost, portable microscopy solutions to enable new and more accessible experiments for biological and analytical applications.

  View details for DOI 10.1371/journal.pone.0306654

  View details for PubMedID 39413076

• DIY liquid handling robots for integrated STEM education and life science research. PloS one Li, E., Lam, A. T., Fuhrmann, T., Erikson, L., Wirth, M., Miller, M. L., Blikstein, P., Riedel-Kruse, I. H. 2022; 17 (11): e0275688

  Abstract

  Automation has played a key role in improving the safety, accuracy, and efficiency of manufacturing and industrial processes and has the potential to greatly increase throughput in the life sciences. However, the lack of accessible entry-point automation hardware in life science research and STEM education hinders its widespread adoption and development for life science applications. Here we investigate the design of a low-cost (~$150) open-source DIY Arduino-controlled liquid handling robot (LHR) featuring plastic laser-cut parts. The robot moves in three axes with 0.5 mm accuracy and reliably dispenses liquid down to 20 muL. The open source, modular design allows for flexibility and easy modification. A block-based programming interface (Snap4Arduino) further extends the accessibility of this robot, encouraging adaptation and use by educators, hobbyists and beginner programmers. This robot was co-designed with teachers, and we detail the teachers' feedback in the context of a qualitative study. We conclude that affordable and accessible LHRs similar to this one could provide a useful educational tool to be deployed in classrooms, and LHR-based curricula may encourage interest in STEM and effectively introduce automation technology to life science enthusiasts.

  View details for DOI 10.1371/journal.pone.0275688

  View details for PubMedID 36350791

• Scientific Inquiry in Middle Schools by combining Computational Thinking, Wet Lab Experiments, and Liquid Handling Robots Fuhrmann, T., Ahmed, D., Arikson, L., Wirth, M., Miller, M. L., Li, E., Lam, A., Blikstein, P., Riedel-Kruse, I., ASSOC COMP MACHINERY ASSOC COMPUTING MACHINERY. 2021: 444-449

  View details for DOI 10.1145/3459990.3465180

  View details for Web of Science ID 000767988500044

• Scale-free vertical tracking microscopy. Nature methods Krishnamurthy, D., Li, H., Benoit du Rey, F., Cambournac, P., Larson, A. G., Li, E., Prakash, M. 2020

  Abstract

  The behavior and microscale processes associated with freely suspended organisms, along with sinking particles underlie key ecological processes in the ocean. Mechanistically studying such multiscale processes in the laboratory presents a considerable challenge for microscopy: how to measure single cells at microscale resolution, while allowing them to freely move hundreds of meters in the vertical direction? Here we present a solution in the form of a scale-free, vertical tracking microscope, based on a 'hydrodynamic treadmill' with no bounds for motion along the axis of gravity. Using this method to bridge spatial scales, we assembled a multiscale behavioral dataset of nonadherent planktonic cells and organisms. Furthermore, we demonstrate a 'virtual-reality system for single cells', wherein cell behavior directly controls its ambient environmental parameters, enabling quantitative behavioral assays. Our method and results exemplify a new paradigm of multiscale measurement, wherein one can observe and probe macroscale and ecologically relevant phenomena at microscale resolution. Beyond the marine context, we foresee that our method will allow biological measurements of cells and organisms in a suspended state by freeing them from the confines of the coverslip.

  View details for DOI 10.1038/s41592-020-0924-7

  View details for PubMedID 32807956

• Bacterial Evolution in High-Osmolarity Environments. mBio Cesar, S., Anjur-Dietrich, M., Yu, B., Li, E., Rojas, E., Neff, N., Cooper, T. F., Huang, K. C. 2020; 11 (4)

  Abstract

  Bacteria must maintain a cytosolic osmolarity higher than that of their environment in order to take up water. High-osmolarity environments therefore present formidable stress to bacteria. To explore the evolutionary mechanisms by which bacteria adapt to high-osmolarity environments, we selected Escherichia coli in media with a variety of osmolytes and concentrations for 250 generations. Adaptation was osmolyte dependent, with sorbitol stress generally resulting in increased fitness under conditions with higher osmolarity, while selection in high concentrations of proline resulted in increased fitness specifically on proline. Consistent with these phenotypes, sequencing of the evolved populations showed that passaging in proline resulted in specific mutations in an associated metabolic pathway that increased the ability to utilize proline for growth, while evolution in sorbitol resulted in mutations in many different genes that generally resulted in improved growth under high-osmolarity conditions at the expense of growth at low osmolarity. High osmolarity decreased the growth rate but increased the mean cell volume compared with growth on proline as the sole carbon source, demonstrating that osmolarity-induced changes in growth rate and cell size follow an orthogonal relationship from the classical Growth Law relating cell size and nutrient quality. Isolates from a sorbitol-evolved population that captured the likely temporal sequence of mutations revealed by metagenomic sequencing demonstrated a trade-off between growth at high osmolarity and growth at low osmolarity. Our report highlights the utility of experimental evolution for dissecting complex cellular networks and environmental interactions, particularly in the case of behaviors that can involve both specific and general metabolic stressors.IMPORTANCE For bacteria, maintaining higher internal solute concentrations than those present in the environment allows cells to take up water. As a result, survival is challenging in high-osmolarity environments. To investigate how bacteria adapt to high-osmolarity environments, we maintained Escherichia coli in a variety of high-osmolarity solutions for hundreds of generations. We found that the evolved populations adopted different strategies to improve their growth rates depending on the osmotic passaging condition, either generally adapting to high-osmolarity conditions or better metabolizing the osmolyte as a carbon source. Single-cell imaging demonstrated that enhanced fitness was coupled to faster growth, and metagenomic sequencing revealed mutations that reflected growth trade-offs across osmolarities. Our study demonstrated the utility of long-term evolution experiments for probing adaptation occurring during environmental stress.

  View details for DOI 10.1128/mBio.01191-20

  View details for PubMedID 32753494