IBM scientists have developed a new lab-on-a-chip technology that can, for the first time, separate biological particles at the nanoscale.
As reported in the journal Nature Nanotechnology, the IBM team’s results show size-based separation of bioparticles down to 20 nanometres (nm) in diameter, a scale that gives access to important particles such as DNA, viruses and exosomes. This research opens up new avenues of medicine as it could enable scientists to detect diseases such as cancer much earlier than was previously possible.
‘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 translational systems biology and nanobiotechnology at IBM Research. ‘Our lab-on-a-chip device could offer a simple, noninvasive and affordable option to detect and monitor a disease, long before physical symptoms manifest. This extra amount of time allows physicians to make more informed decisions and when the prognosis for treatment options 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.
For the research project, IBM is collaborating with a team from the Icahn School of Medicine at Mount Sinai to continue development of this lab-on-a-chip technology.
Results from the project show that it is possible to separate and detect particles as small as 20 nm from smaller particles. In addition, the research demonstrates that exosomes of size 100 nm and larger could be separated from smaller exosomes and that separation can take place in spite of diffusion.
With Mt Sinai, the team plans to confirm their device can pick up exosomes with cancer-specific biomarkers from patient liquid biopsies.
With the ability to sort bioparticles at the nanoscale, Mt 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 could provide valuable insights into the biology of diseases as well as pave the way to non-invasive diagnostic tools.
‘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 Dr Carlos Cordon-Cardo, professor and chairman of the Mount Sinai Health System Department of Pathology. ‘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.’
Lab-on-a-chip technologies have the potential to fundamentally change the way diagnostic tests are carried out as they are often significantly faster, portable, easy to use in addition to requiring less sample volume for a particular test.
IBM is continuing this research into Lab-on-a-chip technologies, IBM scientists Dr Joshua Smith and Dr Benjamin Wunsch, are currently leading work looking at the use of nanoscale deterministic lateral displacement, or nano-DLD. Using this technology, the IBM researchers are creating lab-on-a-chip technology that allows a liquid sample to be passed, in a continuous flow, through a silicon chip containing an asymmetric pillar array.
This array allows the system to sort a microscopic stream of nanoparticles, separating particles by size down to a resolution of tens of nanometers. IBM has already managed to scale the chip size to 2cm by 2cm while continuing development to increase the device density to improve functionality and throughput.