A team of researchers has recently developed a microchip that can detect the type and severity of cancer in patients. As an interdisciplinary pursuit between U of T’s biochemistry and electrical and computer engineering departments, pharmacy faculty, and the Princess Margaret Hospital, the microchip is bound to revolutionize the way we test for cancer.
Pharmacy professor Shana O. Kelley originally envisioned the development of a chip-based platform using an electrocatalytic system (a system using an electrode as a substrate or base for electrochemical reactions) capable of detecting cancer biomarkers (biological molecules particular to each kind of cancer that indicate the presence or absence of that cancer in an individual) in clinical samples.
In order to create this chip-based platform, Kelley sought the help of professor Ted Sargent of the Electrical and Computer Engineering Department. The two obtained funding for the project and oversee a team of 10 graduate students and researchers in various disciplines who are working on improving the chip and using it to test different clinical samples.
PhD students Leyla Soleymani (fourth year Electrical and Computer Engineering) and Zhichao Fang (fifth year Pharmaceutical Sciences) are the two main researchers on the team and published a paper under the supervision of Sargent and Kelley that was featured in Nature Nanotechnology.
Soleymani and Fang have been active in this project since its inception approximately three years ago. The process of using the chip to test for biomarkers equally involves the expertise of Soleymani and Fang. “It was a collaborative effort,” said Soleymani. “I would do something and then get feedback from Fang and others about whether it’s working and usable and then we’d go back and redesign things.
“It’s an electronic chip. It has electrodes that are decorated with nanostructures [that are] functionalized with what we call ‘capture probes.’ They’re like bait attached to the electrode that will capture some biomolecules in the sample or solution we put it in,” described Soleymani. “[The biomolecules] are then associated with a specific type of cancer, which is how it is possible to determine which cancer-related genes are present in the solution.”
The type of probe used on the chip differs depending on the cancer type being tested. “The development of the probe itself is several steps,” added Fang, “but [the length of time needed to develop each probe] depends on the target, for example, how long the target is or how unique the DNA sequence is. We do a lot of experimentation to see if the probe can bind to a target selectively, so once that is accomplished, the rest of the work is [easy].”
Soleymani explained that the chip is composed of a silicon wafer coated and patterned with gold via a process called photolithography. It’s then covered with an insulator (silicon dioxide) resulting in the production of small nanostructures on the chip. The nanostructures are then assembled and functionalized to enable them to grab the target biomarkers from the solution.
This method was used to create the original “first generation” model of the chip, which took approximately one year to produce and was considerably bigger than the current model with significantly fewer electrodes.
“First we put only four electrodes on the chip,” said Fang, “then the number increased to eight and now we have 42.”
Thanks to the team’s collaboration with Princess Margaret Hospital, Soleymani was also able to use the chip to test for brain and neck cancers. “We have clinicians who provide us with samples and help us [prepare them]. We wouldn’t be able to do any of this without this network of researchers,” said Soleymani.
Once the clinical sample is obtained from the Princess Margaret Hospital, Fang is able to use the chip on the clinical sample. Fang explained how he tested for prostate cancer using the clinical sample:
“Once we have accurately detected the target [using some sample solutions created in the lab] we know that we are ready to test the ‘real sample’—the clinical sample. So that’s when we get the sample from Princess Margaret Hospital, which contains the prostate cancer-related gene fusion. Again, the probe is designed to detect the gene fusion sequences, so [if the gene fusion is present], there will be a signal increase which shows the probes have detected the biomarkers for the cancer. Otherwise there will be no signal increase.”
Soleymani and Fang hope to start testing the microchip on other clinical samples as well. “Theoretically, any disease that would have a biomarker that’s a nucleic acid is detectable, so in the future it could be extended to detecting bacterial or viral diseases,” mentioned Soleymani.
Soleymani and Fang’s research is extremely important and will have a profound influence on the medical field. Both students plan on expanding their work in the coming years by testing the microchip on a variety of clinical samples of cancers and disease.
