In 2023, the World Economic Forum in 2023 named bioconvergence a mega trend that will redefine the 21st century. According to an article on the World Economic Forum (WEF) website, biology and data science are on a collision course. But like all collisions, if the right particles of a substance meet in the right orientation, the result will be a successful change.
Imec is on board with this idea and has built its healthcare strategy around bioconvergence. At ITF World 2024 in Leuven, Charlotte D’Hulst, portfolio manager for life sciences at Imec highlighted some of the projects the Belgian research and technology organisation is working on to bring its expertise in semiconductor technology to the world of life sciences.
We have all heard what ChatGPT can do with natural language, said D’Hulst. Biology is another natural language, built on just a few letters that are vastly more complex when assembled into what we call our genetic code.
But, as was pointed out to Imec researchers during a recent Gingko Bioworks Investor Day event, biology is a much more complex problem to tackle and we don’t understand all the rules. Before we can apply the power of large language models (LLMs) to generative AI (GenAI) for biology, we need to gain a better understanding of how biology works and we need to digitise what we already know.
According to D’Hulst, less than 1% of the existing biological data is currently accessible. We need tools to grow that into a data lake of biological information that can be used to train AI algorithms.
The tools would include more sophisticated molecular microscopes that allow us to understand at a deeper level what’s going on inside cells and how cells communicate with one another.
“Imec has helped shine new light on some aspects of biology by looking with unprecedented resolution at the structure of proteins, long-read DNA, and even of the brain,” said D’Hulst.
“But while much progress has already been made using modern technology, such as next-generation sequencing to read biology and CRISPR/Cas9 to edit biology, the advances are only the tip of the iceberg.”
Five areas of bioconvergent technology come into focus
One of the bioconvergent technologies Imec is working on has to do with synthetic biology.
“If we look at the building blocks that are used to develop next-generation therapeutics and in synthetic biology to understand or even create new life, it all comes down to nucleic acids, especially DNA, which makes it a key component of a lot of health-related R&D,” said D’Hulst.
While the cost of DNA sequencing (reading DNA) has dropped by six orders of magnitude over the past 20 years, cost-effective DNA synthesis (writing DNA) remains a challenge. It still costs about the same today as it did 20 years ago.
Imec is also working on scalability, but how technology scales depends on the application. For drug development and synthetic biology, scaling means parallelism –simultaneously producing unique sequences to screen through millions of different candidate solutions. But for precision medicine, where a single dose of medicine is needed for a specific patient, scaling is entirely different.
“We are developing highly scalable schemes addressing electrodes, including post-processing of electrode arrays on application-specific circuits, so manufacturers can control the synthesis of up to hundreds of millions of individual nucleic acids,” said D’Hulst. “Imec is also addressing quantity challenges, increasing the surface on which nucleic acids are being synthesised to increase quantity.”
A third task Imec is doing is to look at ways of customising some of the underlying processes in semiconductor manufacturing to help in healthcare. The research firm is investigating how nanowire meshes, 3D-pillar structures, or nano-imprint lithography can be optimised for bioconvergent applications.
The fourth area of bioconvergence that Imec is investigating is ways of reducing cost. “Here, our fast fluid expertise comes into play, because this allows us to really flush reagents and mix reagents in less than a second, and to perform PCR [polymerase chain reactions] in less than five minutes, with much less reagents, which then has an effect on the cost,” said D’Hulst.
Imec is also working on neuroscience. “For a long time, we have been limited to EEGs, aggregated signals from certain areas of the brain and basic crude deep brain stimulation,” said D’Hulst.
But bioconvergent technologies can now be used to interpret signals among neurons – and Imec is developing three different neurotech platforms. According to D’Hulst, the research organisation has already created high resolution tools that allow practitioners and researchers to study multiple brain structures simultaneously on the level of a single neuron. “Imec has deployed more than 16,000 of these NeuroPixel probes in over 900 research labs globally,” she added.
Imec is developing components for new implants to treat chronic diseases. The implants are miniaturised and wirelessly connected and don’t require batteries. These include neuro-stimulators that can be used to trigger specific parts of the brain. The Belgian research organisation is also looking at non-invasive interfaces with the human brain using, for example, photo-acoustics.
Technology helps to monitor patients
One area where improvement is needed in healthcare is in monitoring patients, ideally in a non-intrusive manner that allows practitioners to observe people as they go about their normal lives.
Along those lines, Imec is introducing a new waveform, speckle plethysmography. Speckles are a form of noise. Coherent light is projected on living tissue, causing particles in the tissue to move, which changes the speckle pattern in ways that provide insight into the underlying tissues and arteries. This can help practitioners observe vital signs such as heart rate, oxygenation, respiration and blood pressure without direct contact.
But perhaps the most intriguing technology that Imec is introducing is the ingestible pill with a wireless antenna to report observations back from within the body. According to D’Hulst, while one out of four people suffer from digestive problems, current methods for finding out what’s going on in the gut (for example, clinical endoscopy or colonoscopy) are expensive and cumbersome and don’t show what’s happening with the patient throughout the day.
D’Hulst said Imec is introducing an intestinal pill, the size of a vitamin pill that can be swallowed. It can be used to measure different things – for example, pH or inflammation – and includes an antenna to transfer data wirelessly from a patient’s intestine. Imec finished the first in-human trial of the ingestible sensor last winter and it is developing a second-generation sensor that can even take samples from the gut.