Title
A Robotic Microscope System To Examine T Cell Receptor Acuity Against Tumor Neoantigens: A New Tool For Cancer Immunotherapy Research
Abstract
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.112.04
Hai Zhu28722.69
Debasis Banik300.34
Zhenping Guan400.34
Yinnian Feng500.34
Ellis L Reinherz6956.10
Matthew J. Lang700.34
H. Harry Asada8856217.74