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Excitable cells in the heart and brain generate fast signals (action potentials) that have to be captured using specialized detectors at over a thousand frames per second. At the same time, the structure of these cells is complex, requiring high resolution detectors and advanced microscopy techniques. We're working on many technologies to help with these issues: three examples - temporal pixel multiplexing, RAP imaging, and remote focusing microscopy - are shown below.

Temporal pixel multiplexing (TPM) is an imaging method that embeds high speed information into still image frames. Camera chips have millions of pixels which integrate charge generated when light hits their surface over a set integration time. TPM controls the way individual pixels are exposed during a single frame to embed high speed information in static images. This allows a lower resolution high speed movie to be extracted, giving a high-res still and a high-speed movie in one shot.

The original TPM prototype was built using a micromirror array (similar to those used in many consumer overhead projectors) to control pixel exposure times in a off-the-shelf camera. We are now developing CMOS sensors that incorporate TPM technology at the pixel level. Unlike other imaging chips which store data every frame, TPM doesn't move data (or transfer charge) during acquisition allowing it to be extremely fast. Our new chips should be able to image activity at over a million frames/second.

Random Access Parallel (RAP) microscopy (previously called solid-state high throughput (SSHTs) imaging) is a new high-throughput brightfield imaging modality that uses an inverted Newtonian telescope architecture with a high speed LED array to image living samples. RAPs advantage comes from being able to change its field of view without any moving parts or robotics. This allows it to switch views so rapidly that you can effectivly image different, spatially separated samples in parallel.

The RAP microscope is optimized for capturing dynamic data from model organisms or macroscopic tissues, such as C. elegans travel and wave propagation in cultured cardiac monolayers. The first RAP prototype, built by three undergraduates in the McGill lab, was able to image four samples simultaneously. Our second generation prototype increased the sample count to 80, and we are currently working on new versions with a range of capabilities.

Remote focusing is a microscopy technique, pioneered by Prof. Tony Wilson's Scanning Optical Microscopy group in Oxford, which allows tissue to be scanned in depth without moving the sample or the imaging objective. When combined with laser scanning two-photon microscopy, the technique allows capture of cell structure and function in living tissue.

Two-photon microscopy uses infrared lasers to image cells in living tissue. Many labs build their own setups allowing them to test new techniques. This is a high-speed remote focusing microscope currently under development.

Remote focusing can be used to measure cell structure in the heart. It does this by measuring two oblique images at 45 degrees to the image plane, and using the measured sarcomere angle to calculate the cell's orientation.

One of the main limitations of scanning microscopes is that they're slow as the laser has to visit each point in an image. We're developing new remote focusing microscopes which split the laser into many beamlets, so we can increase acquisition speed. The aim of this project is to be able to measure cell-cell communication in intact heart and brain tissues.

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