A robotic microscope system to examine T cell receptor acuity against tumor neoantigens: A new tool for cancer immunotherapy research

Lee Ling Sharon Ong*, Hai Zhu, Debasis Banik, Zhenping Guan, Yinnian Feng, Ellis L. Reinherz, Matthew J. Lang, H. Harry Asada

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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 nano-micro 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.

Original languageEnglish
Article number8620519
Pages (from-to)1760-1767
Number of pages8
JournalIEEE Robotics and Automation Letters
Volume4
Issue number2
DOIs
Publication statusPublished - Apr 2019

Keywords

  • Automation at micro-nano scales
  • automation in life sciences
  • biological cell manipulation
  • biotechnology
  • pharmaceutical and health care

Fingerprint Dive into the research topics of 'A robotic microscope system to examine T cell receptor acuity against tumor neoantigens: A new tool for cancer immunotherapy research'. Together they form a unique fingerprint.

Cite this