Tiny testers

Lab-on-a-chip technology is replacing full-scale laboratories for analysing the effects of stimuli on cells

What do mobile phones, PDAs and drug- testing laboratories have in common? They may all be able to fit into the palm of your hand if research at Glasgow University goes according to plan.

Electrical engineers, in collaboration with the Institute of Biology and Life Science, are developing a micro-engineered lab-on-a-chip device that mimics the living cell environment and analyses the effects of mechanical, electrical or chemical stimuli on a cell, which could eventually reduce the need for animal testing.

Dr Huabing Yin, Royal Society of Edinburgh personal research fellow in Glasgow’s department of electronics and electrical engineering, explained how the new technology would offer a quicker, cheaper, more reliable and more controlled method of cellular analysis compared with conventional techniques.

‘Traditionally, in-vitro cellular analysis uses a Petri dish or multi-well plate containing a 2D layer of cells. Using this method, you normally measure tens of thousands of cells in static conditions and get an average response to a stimulus,’ said Yin.

‘However, in-vivo cells live in a dynamically changing 3D matrix, consisting of complex protein and carbohydrate networks with constantly exchanging oxygen and nutrients. Cells sense the chemical and mechanic cues from their local environment and respond correspondingly.

‘This environment can be mimicked in a microfluidic device containing micron and submicron-sized components. This provides more controlled experimental conditions to better understand how the cell responds to different stimuli.

‘Furthermore, cells are individually different and react to stimuli differently. The device we are developing can measure single cells or groups of cells simultaneously to give a database of results instead of just an average.’

Yin claimed the micron-sized components of the device offered greater scope for scientists to control the cellular environment. ‘At its heart, the microdevice consists of a complex network of microchannels, which have dimensions ranging from tens of microns to hundreds of microns,’ she said. ‘They are very compatible with cellular analysis because cells are normally tens of microns in size.’

If the scientists have greater control over the environment surrounding the cell, Yin said the device would produce more reliable readouts, because by mimicking the natural 3D environment that allows cells to be kept healthy, fewer false responses would be returned.

Lab-on-a-chip technology can be adapted for high throughput, which means simultaneous and different biological analyses can take place on the device, which has cost and time advantages over Petri dish or multi-well plate techniques. This is a promising technology for drug development, where economic, high-throughput screening of potential lead compounds is desired.

‘In the traditional multi-well plate assay, drugs are added to the individual well by pipettes. But in the microfluidic device, you can apply a drug simultaneously, to tens or hundreds of arrays of cells,’ said Yin. ‘At the moment, robots are used to do the experiment, which is quicker than using humans, but there is still a problem of variables occurring as the robot still has to pick up the drug and put it on to the wells, whereas with our device, you can control how, when, and at what concentration the drug is inputted.’

This project has benefited from work Yin previously carried out in collaboration with the GlaxoSmithKline and LGC pharmaceutical companies.

‘From our previous work, we understood the importance of controlling the cell’s local microenvironment in retrieving reliable responses from the cells,’ she said. ‘This project is not just an extension of that work, although it will still be applied in the field of drug development.

‘With the infusion of expertise in the field of tissue engineering and adult stem cells from the Cell Engineering Centre in the Institute of Biology and Life Science, we expect to have a new approach to understand and influence cell growth and differentiation.’