When we look at biological cells under the microscope, they are usually not very colourful. Usually, to visualize them we have to artificially add color – usually by blurring. By doing this, we can see their shape and arrangement in the tissue and determine whether they are healthy.
Sometimes, however, cell structure alone is not sufficient to correctly identify the disease – which can lead to misdiagnosis and potentially fatal consequences for the patient. But what if there was a way to not only look at the structure of cells, but also determine whether they are abnormal, simply by looking at their internal color under a microscope?
This was the goal of our team as we developed a new medical diagnostic tool called NanoMslide. We modified a standard microscope slide to turn it into a powerful tool for detecting breast cancer. Our research is published today in Nature.
early detection is important
It is estimated that one in eight Australian women will be diagnosed with breast cancer by the age of 85. As with most cancers, catching the disease early is important. However, accurate diagnosis of the early stages of breast cancer requires the identification of small numbers of diseased cells throughout the tissue, which can be incredibly challenging.
The NanoMslide can manipulate light at the nanoscale, allowing cells to “light up” with vivid color contrast. This makes it easier to identify potential cancer cells (or benign abnormalities) within the tissue.
By providing a way to quickly identify which cells may become cancerous, the tool could help reduce the current uncertainty around detecting very early-stage breast cancer. As with mammogram screening, it is very important to differentiate breast abnormalities from early breast cancer on biopsy, especially as the misdiagnosis rate can be as high as 15%.
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major barriers to development
Incorporating nanotechnology in medical diagnostics presents several challenges. It took us six years to make sure the NanoMslide would work effectively. In the end it was a combination of state-of-the-art nanofabrication, a significant amount of trial-and-error and a little bit of luck that led to our success.
For decades, researchers have known that cancer cells interact with light in a way that is different from healthy cells. This is due to a number of factors, such as the distribution of proteins within the cell and differences in its overall shape.
The main challenge is that these differences can be extremely subtle and present in different ways. Previous approaches (without using stains or labels) to isolate cancer cells have tended to use specialized microscopy equipment, or complex techniques.
But incorporating these approaches into existing pathology workflows is difficult and may require specialist training and knowledge. So we took a fundamentally different approach.
success with human tissue
Instead of focusing on developing a better microscope, we instead focused on improving the microscope slide.
By developing a special nanofabricated coating, we modified the surface of a simple microscope slide and turned it into a giant sensor. What is truly remarkable is that the structures of the sensors are just a few hundred nanometers across, yet replicate with amazing accuracy in the region of ten centimeters or more.
Maintaining this level of accuracy, which is essential for reliable fabrication at this scale, has led to advances in nanofabrication techniques that have only become commercially available in the past six years.
The sensor is activated by visible light. And when an object such as a tissue or a single cell comes into contact with the surface of the sensor, colors are produced. It is this feature that we have been able to adapt to allow pathologists to detect potential cancer cells simply by looking at them.
Dyes that are currently used to stain tissues (to visualize cell shape and architecture) usually exist as one or two dyes. NanoMslide renders tissues in beautiful full-color contrast, making it easy to isolate multiple cell types on a single slide.
For our study, we tested slides with specialist breast-cancer pathologists using both mouse models and patient tissue. By starting with a well-characterized small-animal model, our team of physicists, cancer researchers and breast pathologists was able to further develop the technology.
We eventually reached the point where we could be sure that some of the distinctive colors that appeared were signs of cancer cells. This led to further pathology evaluation with patient tissue, where there is more complexity to contend with in terms of diagnosis.
Nevertheless, even in this more challenging setting, the NanoMslide performed strongly. It also outperformed some commercial biomarkers, which are used as aids for borderline diagnosis (where cancer is difficult to tell apart from benign abnormalities).
like moving from black and white to color television
Since the technology is not dependent on any particular function, or specific molecular interactions, it could potentially be applied to other types of cancer – even other types of diseases. Another application that is now being worked on is to examine the results of a liquid biopsy, such as a cheek swab, for immediate point-of-care analysis.
In April, we were fortunate enough to benefit from the opening of a new equipment at the Australian National Manufacturing Facility to enable the scaling-up of production. This means that NanoMslide can be taken from small-scale to medium-scale manufacturing, allowing us to explore many different applications, and by producing the number of slides needed for further clinical validation. can.
The technology could also be hugely beneficial to the growing digital-pathology space, where the vivid colors generated by nanomuslides could help develop next-generation artificial intelligence algorithms to identify disease symptoms.
Read more: Curious Kids: Why do people get cancer?