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Updated: Mar 11, 2026
Visualizing Lymph Node Structure and Cellular Localization using Ex-Vivo Confocal Microscopy
Published on: August 9, 2019
Spatially resolved microfluidic stimulation of lymphoid tissue ex vivo
Ashley E Ross1, Maura C Belanger, Jacob F Woodroof
1University of Virginia, Dept. of Chemistry, PO Box 400319, McCormick Rd, Charlottesville, VA 22904, USA. rpompano@virginia.edu.
Insights
Researchers developed a novel lymph node slice-on-a-chip system for precise local stimulation and analysis. This platform enables targeted drug delivery and study of immune responses within lymph node substructures, aiding immunotherapeutic development.
Area of Science:
- Immunology
- Microfluidics
- Biomedical Engineering
Background:
- Lymph nodes are critical immune organs, but their complex structure hinders precise study of local cellular responses.
- Current methods lack the ability to stimulate specific lymph node substructures or analyze localized stimulus-response behaviors, impeding the design of targeted therapies for inflammatory diseases.
Purpose of the Study:
- To develop a novel platform integrating live lymph node slices with microfluidics for precise local stimulation and analysis of lymph node substructures.
- To enable targeted delivery and study of therapeutic agents within specific regions of the lymph node.
Main Methods:
- Integration of live lymph node slices with a 3-layer polydimethylsiloxane microfluidic device.
- Delivery of fluorescent dextrans (40 and 70 kDa) to live lymph node slices with high spatial resolution (284 ± 9 μm and 202 ± 15 μm).
- Utilized a computational model to predict and control the spread and quantity of stimulation via varying flow rates.
Main Results:
- The lymph node slice-on-a-chip system maintained tissue architecture and allowed experimental access to lymph node core.
- Precise spatial resolution delivery of substances (284 ± 9 μm and 202 ± 15 μm) was achieved within seconds.
- Demonstrated simultaneous dual-region stimulation and differential drug retention (e.g., glucose-conjugated albumin) in B-cell vs. T-cell zones.
Conclusions:
- The developed lymph node slice-on-a-chip platform offers unprecedented control for targeting and studying local events within the lymph node.
- This technology provides a valuable tool for understanding immune responses and informing the rational design of novel immunotherapeutics for inflammatory conditions.
Abstract:
The lymph node is a structurally complex organ of the immune system, whose dynamic cellular arrangements are thought to control much of human health. Currently, no methods exist to precisely stimulate substructures within the lymph node or analyze local stimulus-response behaviors, making it difficult to rationally design therapies for inflammatory disease. Here we describe a novel integration of live lymph node slices with a microfluidic system for local stimulation. Slices maintained the cellular organization of the lymph node while making its core experimentally accessible. The 3-layer polydimethylsiloxane device consisted of a perfusion chamber stacked atop stimulation ports fed by underlying microfluidic channels. Fluorescent dextrans similar in size to common proteins, 40 and 70 kDa, were delivered to live lymph node slices with 284 ± 9 μm and 202 ± 15 μm spatial resolution, respectively, after 5 s, which is sufficient to target functional zones of the lymph node. The spread and quantity of stimulation were controlled by varying the flow rates of delivery; these were predictable using a computational model of isotropic diffusion and convection through the tissue. Delivery to two separate regions simultaneously was demonstrated, to mimic complex intercellular signaling. Delivery of a model therapeutic, glucose-conjugated albumin, to specific regions of the lymph node indicated that retention of the drug was greater in the B-cell zone than in the T-cell zone. Together, this work provides a novel platform, the lymph node slice-on-a-chip, to target and study local events in the lymph node and to inform the development of new immunotherapeutics.
