02 Apr 2007
US researchers have designed a laser-based holographic imaging system to monitor what happens to a cancerous cell as an anti-cancer drug is administered.
According to David Nolte of Purdue University, the experiment uses a technique known as digital holographic optical imaging to detect movements within a cell to a resolution of 100 nm. "Our experiment is aimed at determining a direct physiological measure of what a drug is doing inside cancer cells,” Nolte told optics.org. The technique could have important uses in drug testing and biotechnology.
In the experiment, cancerous cells in a Petri dish are irradiated with light from a 800 nm, 100 fs titanium-sapphire laser. Light from the laser is split into two: a reference beam is directed to a CCD camera, while the other laser beam is directed towards the tumour. Light reflecting off the tumour then interferes with the reference beam to produce a hologram, which appears on a computer screen as a series of bright and dark speckled spots.
This pattern of bright and dark blotches changes as the contents of the cancer cells move. "All living matter is in constant motion, and the laser speckle from a living object is constantly changing with that motion,” explained Nolte. “The image appears to ‘shimmer’ with the motion inside the cell.”
Information about cellular motility (or movement) is obtained by carefully analysing the speckles that show up on the sensor. Even though the cells’ constituents are of sub-wavelength dimensions, the effect of their motion can be detected by rapidly photographing the interference pattern created by their motion. "It’s amazing that we can say which part of the cell is moving just by looking at these speckles."
Of particular interest are the organelles – complex structures inside a cell that perform specialized functions. When organelles move inside a cell, they can facilitate the process of mitosis, where a cell divides itself into two identical daughter cells. Antimitosis drugs, used in cancer therapy, seek to stall this cell division process by blocking this internal movement.
The Purdue technique – which was first presented by Nolte at the American Physical Society Meeting in Denver, Colorado, at the beginning of March – is therefore designed to determine the degree of activity inside a cell. “As the anticancer drug works, there is less motion inside the cell and the shimmer effect is reduced. Even if the organelle moves by about 100 nm, we will be able to detect it,” said Nolte.
Although holographic technology has been available for some time, technical challenges have prevented researchers from recording and analysing the images in real time. Special semiconductor films have until recently been used to produce such holographic images, but they are expensive to fabricate and do not make it possible to snap the thousands of images that are needed to chart real-time activity on the cell level.
Now, however, rapid advances in digital cameras have made it possible to use a much cheaper CCD sensor for the entire recording. "It’s quite exciting. We have gone from taking a photograph of the tissue to making a movie (well almost) of cellular action."
Nolte elucidates complex biological processes about cell division and cancer therapy with ease and confidence, even though his training is in physics. "It’s been a fun learning experience for me," he told optics.org. Invaluable contributions to the project were made by John Turek, a specialist in biological sciences, and graduate assistant Kwan Jeong.
It will take some time for an imager of this type to be incorporated into a device that peers inside our bodies, but in the meantime the technique could have two potential applications in drug testing. "In one case, we can see how fast an antimitotic drug brings intracellular activity in tumour cells to a stop, and in the other case we can observe the toxic impact that a drug has on healthy tissue (i.e. side effects)," explained Nolte.
Next on the team's agenda is taking similar measurements on the cytoskeleton, which acts as the cells’ support structure. "We want to find out what types of motion influence the shimmer effect, so that we can find more applications for this in biotechnology and medical diagnosis," concluded Nolte.