History of CBIS

A History of the NUS Centre for Bioimaging Sciences

An interdisciplinary research centre for leading-edge microscopy & computatioN

Founded in 2008, and opened in its current premises in 2010, CBIS was created as an interdisciplinary research centre combining existing groups in light, electron, and scanning probe microscopy into a centre to study the basic structure and dynamics of cellular systems over wide temporal and spatial ranges. CBIS acts especially in areas that offer collaboration with large-scale research programs such as Cancer RCE, SBIC, SMART Infectious Disease IRG, and mechanobiology.

Original whitepaper for the founding of CBIS (PDF)

About the Centre

CBIS’s Objective: to bring together an interdisciplinary group of biologists, chemists, computer scientists, mathematicians and physicists, all with a common belief; that complex cellular processes can be probed and captured with sophisticated imagining techniques, and then understood through powerful computational methods.

CBIS’s Mission by Founding Director, Paul Matsudaira

Through the centuries, discoveries have built on discoveries, and knowledge has built on knowledge. Technology has opened avenues of exploration never before conceived. Then there is the present. We are living in an exciting time, when we have both the awareness and expertise to explore ever-expanding scales of knowledge about molecules and cells, and the technology to make it possible. In particular, advances in imaging have catalyzed advances in biology. The NUS Centre for BioImaging Sciences was founded to develoop and apply novel imaging technologies to key problems in biology.

Recent advances in biology, chemistry, computer sciences, and physics –and the remarkable evolution of microscopes and computation– enable us to watch single molecules in action, create three-dimensional images of molecules over time, and observe them in live cells and tissues. Biomolecular imaging has not only gone far beyond its earlier capabilities, it has also surpassed other traditional methods of cellular research. Now we have the means to delve into systems-scale questions, observing many different molecules – and the structures they comprise – simultaneously and in real time.

CBIS is working to find new answers as well as ask new questions that enhance our understanding of the most complex issues in biology. We invite you to explore the Centre for BioImaging Sciences, and to join us in applying our tools, resources, and expertise to the microscopic mysteries that await discovery.

History of CBIS’ CryoEM Facility

The department first introduced electron microscopy at NUS in 1984 when the Government of Japan presented a JEOL JEM 100 CXII STEM equipped with X-ray Microanalysis attachment and other sample preparation equipment. It was at that time the most up-to-date facility in Singapore and it served the whole of the Science Faculty and other institutes, such as SGH.

This equipment analysed a wide range of biological and physical samples from unicellular organisms to tissues of both botanical and zoological nature and from nanoparticles to geological samples. It continues to be used by research personnel from many faculties and departments of NUS and industry.

Challenges to building the new facility

Prior to renovation, the Microscopy Facility experienced two major problems. The high relative humidity of the tropics caused instantaneous ice crystal formation on cryo-samples. This spurious ice contaminant coated the cryosamples and prevented structure determination in the electron microscope.

An equally serious problem was that a nearby building power and ground cables generated extremely high electromagnetic interference, EMI, which distorted the electron beam of all the TEMs and prevented them from reaching their full performance specifications.

JEOL and FEI engineers determined the sources of the EMI and contributed to the design of the Cryoelectron Microscopy Facility. As a result, the Facility was designed to support high-end cryoelectron microscopy by reducing humidity to 30% RH in the microscope and sample preparation rooms and by minimizing EMI by moving the power and ground lines for buildings S1, S2, S3, and S4 a suitable distance away from the Cryo Facility

After renovation, the Microscopy Facility was reorganized into the Cryoelectron Microscopy Facility by moving non-cryo-related functions to other sites including a scanning electron microscope to the TMSI and light microscopy support to building S1A.

Acquisition of the Titan Krios

The flagship instrument of the Facility is the FEI Titan Krios. Fully automated, the microscope lies within an outer box to give its iconic shape and shield the microscope from fluctuations in temperature and acoustic noise.

An autoloader feeds up to twelve samples into the specimen holder for imaging at liquid nitrogen temperatures. The microscope is operated remotely from a station located outside the microscope room. Images are collected by a 4K x 4K Gatan CCD camera after post-filtering through a Gatan GIF. Shortly after installation, the Krios was collecting high-resolution images of viruses and other biological specimens. This multi-million dollar instrument was purchased by funds from the Lee Hiok Kwee Fund.