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Cells are the basic functional units of all living organisms. The current understanding of individual cell mechanisms is still in its infancy. A significant hurdle that severely restricts current cellular studies is the lack of efficient cell manipulation tools that can be used for probing, testing and controlling cellular behavior with micro/nano level precision.

Prof. Dong Sun and his optical tweezers cell manipulation system

In this research, generic cell manipulation tools have been developed and employed to investigate the cell properties. Whole cell manipulation tools and function characterization are made possible by the development of a Cell Bio-Probe, which integrates robotics, optical tweezers, and microfluidics in a sophisticated automated cell testing system. Robotics has been a proven tool for object manipulation for decades, and has recently been extended to MEMS devices in combination with microfluidics lab technology. Optical tweezers is an emerging technology, utilizing a highly focused low-power laser beam to trap and move suspended objects with micro/nanometer size, providing an unparalleled means for studying the biomechanical properties of a large variety of medically significant nonadherent cells. The integration of optical tweezers into a robot-aided manipulation system, where optical tweezers function as specialized effectors to manipulate one or many cells simultaneously, will open up a new dimension for probing, testing and controlling cellular behaviors at the single cell level.

The developed cell manipulation tools, as seen in the figure, have been utilized to manipulate cells in various operations, which include cell stretching, cell transportation, cell sorting, cell adhesion and cell fusion. An automated system, using vision feedback, permits tests on cells to be carried out with a high degree of repeatability. This is significant, as much of the testing that has been reported in other works has been conducted under manual control, with a high degree of variability. Being able to conduct highly repeatable tests is critical to obtain consistent research results. Further, the system permits the simultaneous test of many cells to characterize the cell properties. Microfluidic channels with MEMS based actuated gates will permit the flow of suspended cells to be controlled, allowing groups of cells to be positioned for simultaneous processing. Control methods will be utilized to control the motion of cells, for conducting simultaneous tests and procedures on multiple cells.

Robot manipulation system with optical tweezers

The developed cell manipulation system has been utilized to probe cell functional mechanism of hematopoiesis as an application example. Hematopoiesis is a highly conserved and critical process that arises from and is sustained by a rare population of hematopoietic stem progenitor cells (HSPC). Abnormal regulation of HSPC leads to serious and life-threatening human diseases including acute myeloid leukemia (AML). AML, one of the most lethal cancers in adults, affects approximately one in every 250 people, with only 30% of patients cured with conventional chemotherapy and allogeneic bone marrow transplantation. Currently, a research team in CityU, led by Prof. Dong Sun, is collaborating with the University of Hong Kong towards the studies of: i) probing mechanobiological properties of hematopoietic cells with reference to its link to abnormal differentiation, through cell stretching manipulation; and ii) probing molecular mechanism regulating the interactions between hematopoietic and stromal cells, through cell adhesion manipulation.

The new generic research tools will allow the testing and characterization of a great many biological cells of interest to researchers. Automated robotic control of the optical tweezers will create a consistent experimental framework allowing various experimental procedures to be carried out in a reproducible manner for many trials or with many cells simultaneously. The characterization study at the single cell level will provide important mechanistic insights to the disease process that could not be done with bulk tissue evaluation.

Prof. Dong Sun supervised the students in using the optical tweezers system

Prof. Dong Sun
Department of Mechanical and
Biomedical Engineering
City University of Hong Kong