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| Content Provider | Royal Society of Chemistry (RSC) |
|---|---|
| Author | Belanger, Maura C. Ross, Ashley E. Pompano, Rebecca R. Woodroof, Jacob F. |
| Copyright Year | 2017 |
| 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. |
| Starting Page | 649 |
| Ending Page | 659 |
| Page Count | 11 |
| File Format | HTM / HTML PDF |
| ISSN | 00032654 |
| Volume Number | 142 |
| Issue Number | 4 |
| Journal | The Analyst |
| DOI | 10.1039/c6an02042a |
| Language | English |
| Publisher | Royal Society of Chemistry |
| Access Restriction | Open |
| Subject Keyword | Isotropy B cell Lymph node Perfusion T cell Micrometre Albumin Diffusion Polydimethylsiloxane Convection Immune system |
| Content Type | Text |
| Resource Type | Article |
| Subject | Spectroscopy Environmental Chemistry Analytical Chemistry Biochemistry Electrochemistry |
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