Title | ||
---|---|---|
A Robotic Microscope System To Examine T Cell Receptor Acuity Against Tumor Neoantigens: A New Tool For Cancer Immunotherapy Research |
Abstract | ||
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During immune surveillance, cytotoxic T lymphocytes (CTL) can selectively identify and destroy tumor cells by recognizing tumor-specific peptides (neoantigens), bound to major histocompatibility complex molecules (pMHC) arrayed on cancer cell surfaces. CTL use the same machinery to destroy virally infected cells displaying pathogen-specific pMHC, while leaving intact healthy cells expressing normal self-pMHC. We present a robotic microscope that allows scientists to conduct highly sensitive and selective T cell-pMHC studies with high throughput. Our system manipulates micro-meter beads coated with particular pMHC, presents them to T cells and generates piconewton level intermolecular forces required to detect T cell acuity with a neoantigen. Our system integrates optical tweezers, precision nanomicro stages, and episcopic/diascopic illumination schemes at two magnifications. We create a coordinate referencing system to locate translucent T cells in three-dimensional, over a large space, based on the characteristic intensity change at each focal plane caused by the cells. Our system performs automated experiments to detect the level of T cell acuity with specific pMHCs, by measuring the downstream cellular responses. High acuity T cells can be selectively recovered for single cell analysis. Our new methodology and tool will have a significant impact on cancer immunotherapy and immunology research. |
Year | DOI | Venue |
---|---|---|
2019 | 10.1109/LRA.2019.2894466 | IEEE ROBOTICS AND AUTOMATION LETTERS |
Keywords | Field | DocType |
Automation at micro-nano scales, automation in life sciences, biotechnology, pharmaceutical and health care, biological cell manipulation | Cancer immunotherapy,Cancer cell,Control theory,Cell biology,Major histocompatibility complex,Immune system,Engineering,Cytotoxic T cell,Single-cell analysis,CTL*,T cell | Journal |
Volume | Issue | ISSN |
4 | 2 | 2377-3766 |
Citations | PageRank | References |
0 | 0.34 | 0 |
Authors | ||
8 |
Name | Order | Citations | PageRank |
---|---|---|---|
Ong, L.-L.S. | 1 | 1 | 2.04 |
Hai Zhu | 2 | 87 | 22.69 |
Debasis Banik | 3 | 0 | 0.34 |
Zhenping Guan | 4 | 0 | 0.34 |
Yinnian Feng | 5 | 0 | 0.34 |
Ellis L Reinherz | 6 | 95 | 6.10 |
Matthew J. Lang | 7 | 0 | 0.34 |
H. Harry Asada | 8 | 856 | 217.74 |