Research Projects

The Application and Development of Optical Measurement Technologies for the Optimisation and Automation of Stem Cell Culture

This work is a collaboration between SIMTech and the Bioprocessing Technology Institute. It is focused on the application and development of optical measurement technologies for the optimisation and automation of stem cell culture.


Contact PersonLi Xiang, Leon()
Solution

There is a pressing need to address the design of automated bio-reactors to manufacture quality controlled stem cells. This is a research focus of the Stem Cell group at the Bioprocessing Technology Institute (BTI). This research collaboration is applying SIMTech’s expertise in the area of optical measurement and automation to develop tools for the measurement tasks associated with the optimisation of the stem cell growth process. An important goal is the eventual expression of this capability as a monitoring system for a bio-reactor to generate production volumes of clinically applicable stem cells. To achieve non-destructive measurement optical methods are being developed to allow non-contact monitoring of live cells contained within standard plastic growth vessels. 

An imaging system has been developed for continuous measurement of live, unmodified, human embryonic stem cells. The system is an automated platform which can capture uniform pictures of growing clusters of cells. An adaptive non-linear lighting is developed to obtain clear images. Images of cell growth are captured and analyzed to extract total cell area using proprietary algorithms. The specific growth rate can be determined. The spatial distribution of clusters on the plate can be mapped. The individual cluster can be traced from day one to day two. The measurement will not affect cell growth, structure and sterility  The stem cell imaging system (SCIS) can be used to support the optimization of automated stem cell growth for in-vitro study and for high-volume bio-manufacture.  The whole system is calibrated with measurement microscope and haemacytometer.

Benefits

A non linear lighting system was developed to obtain good contrast, uniform images of the weakly scattering cells without overexposure of the cells.


Patents / Awards / Achievements / Differentiation

A non linear lighting system was developed to obtain good contrast, uniform images of the weakly scattering cells without overexposure of the cells.


Applications
  • To measure the cell numbers in the growing cycle, calculate the doubling time, growth rate etc
  • To quantify cluster size distribution profiles
  • To map clusters on dish
  • To quantify individual cluster sizes and identify optimum cluster sizes
  • To quantify growth of other embryonic stem cells such as mouse, primate and rat species
  • To quantify growth of differentiated cluster cultures such as embryod bodies, cardiomyocytes, pancreatic islets and neural stem cells

 

Problems Addressed

In recent years the promise of stem cells and the area of regenerative medicine has been widely publicised with clinical trial results already showing remarkable results in the treatment of many age and disease related conditions. A major obstacle to the wide spread use of such therapies is the large numbers of cells needed to treat a patient and the technical difficulties in producing such large volumes at high quality. As an illustration it is estimated that to provide insulin islet transplant material for an adult male of 70kg would require over 10^11 cells (9000 islets per kg and 2x105 cells per islet). With current stem cell culture capabilities it is possible to harvest about 1.6x10^6 cells from a standard Petri dish after a growing time of about a 7 days. We are therefore still 5 orders of magnitude away from the quantities that may be needed for clinical use. It is also critical that the quality of these cells is monitored to detect any signs of anomalous growth rates that may indicate tumour development.