New device tracks chemical signals within cells

Researchers have invented a new device that quickly and accurately tracks chemical signals which tell cells how to multiply, an advance that could help identify new targets for cancer medications.
Throughout the human body, certain signalling chemicals - known as hormones - tell various cells when to grow, divide and proliferate. However, not all cells respond to these signals in the same manner.
In rare instances, the internal chemical response of a cell can cause unregulated cell growth, leading to cancer.
To look into the responses of different cells, researchers at the University of Toronto harnessed the emerging power of digital microfluidics, which involves shuttling tiny drops of water around on a series of small electrodes that looks like a miniature checkerboard.

The researchers were able to increase the speed at which chemical changes can be detected by a factor of 100.
"By applying the right sequence of voltages, we can create electric fields that attract and move around droplets containing any chemical solution," said first author Alphonsus Ng who recently graduated with a PhD from the U of T Institute of Biomaterials and Biomedical Engineering (IBBME) and Donnelly Centre.

The team's method allows the scientists to deliver a quick-fire sequence of chemicals to small groups of cells stuck to the surface of the board.
For example, the first drop might contain a hormone that tells cells to grow faster. Within seconds, this hormone sets off a chain reaction called a "phosphorylation cascade," modifying certain proteins within the cell in a specific sequence.

To see these changes, scientists deliver a second drop containing formaldehyde, which freezes all the proteins in place. They then deliver a third drop containing fluorescent antibodies that stick only to the proteins modified in the cascade.
Looking at the antibodies in a microscope provides a snapshot of what has changed and what has not.
By building up a series of snapshots at different time intervals, scientists can see how the cascade progresses.
Using sequences of chemicals to measure how cells respond to a hormone is nothing new. But until now, scientists were limited by how fast they could add each chemical in the sequence.

The team tested the technique on a type of breast cancer cells.
"Roughly 10 per cent of the cells had a very rapid and strong response that we could detect up to five minutes before the rest of the population," said Chamberlain.
The team speculates that these "rapid responders" may be involved in the early stages of tumour generation, although more research is needed to confirm this.
While scientists have long suspected that some cancer cells respond to signals faster and more strongly than others, the new device offers a way to study such cells in unprecedented detail.