IBM scientists have developed a new lab-on-a-chip technology that can, for the first time, separate biological particles at the nanoscale and could help enable physicians to detect diseases such as cancer before symptoms appear.
Reported in the journal Nature Nanotechnology, the IBM team’s results show size-based separation of bioparticles down to 20 nanometers (nm) in diameter, a scale that gives access to important particles such as DNA, viruses and exosomes. Once separated, these particles can be analysed to potentially reveal signs of disease even before patients experience any physical symptoms and when the outcome from treatment is most positive. Until now, the smallest bioparticle that could be separated by size with on-chip technologies was about 50 times or larger, for example, separation of circulating tumour cells from other biological components.
IBM is collaborating with a team from the Icahn School of Medicine at Mount Sinai to develop this lab-on-a-chip technology and plans to test it on prostate cancer, the most common cancer in men in the US.
In the era of precision medicine, exosomes are increasingly being viewed as useful biomarkers for the diagnosis and prognosis of malignant tumours. Exosomes are released in easily accessible bodily fluids such as blood, saliva or urine. They represent a precious biomedical tool as they can be used in the context of less invasive liquid biopsies to reveal the origin and nature of a cancer.
The IBM team targeted exosomes with its lab-on-chip technology as existing scientific techniques face challenges for separating and purifying exosomes in liquid biopsies. Exosomes range in size from 20-140nm and contain information about the health of the originating cell that they are shed from. A determination of the size, surface proteins and nucleic acid cargo carried by exosomes can give essential information about the presence and state of developing cancer and other diseases.
IBM’s results show they could separate and detect particles as small as 20 nm from smaller particles, that exosomes of size 100 nm and larger could be separated from smaller exosomes, and that separation can take place in spite of diffusion, a hallmark of particle dynamics at these small scales. With Mount Sinai, IBM plans to confirm their technology is able to pick up exosomes with cancer-specific biomarkers from patient liquid biopsies.
“The ability to sort and enrich biomarkers at the nanoscale in chip-based technologies opens the door to understanding diseases such as cancer as well as viruses like the flu or Zika,” said Gustavo Stolovitzky, program director of Ttanslational systems biology and nanobiotechnology at IBM Research. “This extra amount of time could allow physicians to make more informed decisions and when the prognosis for treatment options is most positive.”
With the ability to sort bioparticles at the nanoscale, Mount Sinai hopes that IBM’s technology can provide a new method to eavesdrop on the messages carried by exosomes for cell-to-cell communications. This can elucidate important questions about the biology of diseases as well as pave the way to noninvasive and eventually affordable point-of-care diagnostic tools. Monitoring this intercellular conversation more regularly could allow medical experts to track an individual’s state of health or progression of a disease.
“When we are ahead of the disease we usually can address it well; but if the disease is ahead of us, the journey is usually much more difficult. One of the important developments that we are attempting in this collaboration is to have the basic grounds to identify exosome signatures that can be there very early on before symptoms appear or before a disease becomes worse,” said Carlos Cordon-Cardo, chair of the department of pathology at the Mount Sinai Health System and professor of pathology, genetics and genomic sciences, and oncological sciences at the Icahn School of Medicine. “By bringing together Mount Sinai’s domain expertise in cancer and pathology with IBM’s systems biology experience and its latest nanoscale separation technology, the hope is to look for specific, sensitive biomarkers in exosomes that represent a new frontier to offering clues that might hold the answer to whether a person has cancer or how to treat it.”