Microfluidics is rapidly gaining traction in areas like medical diagnostics, cell engineering, and therapeutics. Innovative devices now offer faster results, reduced costs, and the ability to work with extremely small sample volumes compared to traditional methods. But, as the microfluidics market is set to rise rapidly to over USD 100 Billion by 2033, how is Belgian innovation contributing to this burgeoning field and what can we expect from microfluidics-based solutions for diagnostics and cellular therapeutics of the future?
The power of the microfluidic lab-on-a-chip
Healthcare practitioners use diagnostic tests to help them link disease characteristics to a patient’s condition or to guide their treatment decisions based on the particular cell types or biomarkers identified. In diseases such as cancer, results from diagnostics might lead to cell-based treatments like CAR T-cell therapy, where scientists modify patient-derived T-cells in the lab to attack tumor cells in the patient’s body.
In both diagnostics and cell-based therapies, the correct cells must be isolated from a patient’s blood. Current methods of sorting cells are often based on flow cytometry but rely on expensive instruments with high operating costs, need highly trained operators, have low scalability, and long turnaround times.
Luckily, microfluidic devices have what it takes to overcome these barriers. “Microfluidic chips offer a very modular approach,” says Sarah Libbrecht, senior bio-application scientist at imec in Leuven, Belgium, an international leader in research and development of nanoelectronics and digital technologies. This modularity makes it possible to scaleup by adding more channels to a chip, use multiple chips to match the desired sample throughput, or even combine chips designed for different jobs. “Chips for different stages of the process can easily be combined. The global scientific community has developed solutions to identify different types of cells, to sort them, and to track them, so we can now think about how to click all those modules together,” continues Libbrecht.
The outcome is a highly efficient, full-service, customizable lab-on-a-chip. Such integrated solution will reduce the risk of human error and contamination associated with traditional approaches where scientists must manually move cells between different process steps such as cell sorting, manual medium exchange in culture flasks, and cell expansion in an incubator. “With modular approaches, you go from batch-in to batch-out and that makes a world of difference,” emphasizes Libbrecht. Furthermore, it increases automation and scalability, which are crucial to bring rapid bedside diagnostics closer to the clinic and streamline the efficient processing of billions of cells required for groundbreaking cell therapeutics like CAR T-cell therapy, where time is everything.
Microfluidics in action
Sorting healthy cells that meet clinical and regulatory requirements are the foundation of effective CAR T-cell therapies, so addressing cell recovery after sorting with standard methods is crucial. “After sorting, we want the cells to exert their biological function, but if something happens during the process that changes their function, your therapeutic will not be as effective,” says Libbrecht. “The key is to make cells as comfortable as possible during the sorting process so that they don’t really feel like they’ve been sorted at all.”
To achieve this, the team from imec developed a gentle microfluidic cell sorting device called a bubble jet sorter. On the chip, microbubbles are formed that gently make waves in the fluid that contains the cells. The cells then ride these waves down a defined microfluidic channel, thereby separating the cells of interest from the rest of the sample based on specific cell markers detected by lasers. The researchers compared their gentle sorting device to magnetic bead cell sorting and found that it achieved a similar purity and cell viability but with an increased cell recovery rate that would benefit cell therapy approaches.
In another proof-of-concept project, Libbrecht was driven by discussions with clinicians who struggled to retrospectively adapt or improve treatment of ovarian cancer. This was largely due to the cumbersome way data on the immune system are currently gathered using classical flow cytometry methods. In most hospitals, high-end equipment is not available, or it’s located in a core facility staffed by highly trained personnel. “To overcome this issue, clinicians need a rapid, non-invasive test which can be done at regular time points, without the need for intervention from a technology specialist,” says Libbrecht.
To offer clinicians better guidance and more informed development of immunotherapies in a personalized way, Libbrecht and colleagues developed a microfluidics device to monitor the immune system of ovarian cancer patients at point-of-care. The proof-of-concept device matched conventional diagnostic systems in sensitivity and accuracy, but without the need for specialized staff or expensive equipment.
Multidisciplinary microfluidics
Microfluidics is an inherently multidisciplinary field, integrating physics, engineering, chemistry, and biology to create powerful but easy-to-use devices. Researchers are now also combining advances in other disciplines into microfluidic chips with exiting results. “I think that incorporating multiple disciplines in one powerful chip is the technology of the future,” explains Libbrecht. For instance, researchers from imec, in collaboration with the Austrian startup Sarcura, recently demonstrated how a microfluidics chip with integrated photonics could reliably distinguish between two different types of human white blood cells, called lymphocytes and monocytes, for cell therapy applications.
Similarly, the power of artificial intelligence (AI) also stands to benefit the field as a whole, alongside downstream diagnostic and clinical users. “AI will put an extremely powerful layer on top, where the whole process can benefit,” predicts Libbrecht. However, while AI holds immense promise, the field remains in its infancy and there’s a lot of biology that is required to validate what AI predicts in terms of cellular morphologies and sample heterogeneity. “Future AI-enhanced lab-on-chip microfluidic devices might one day tell us why one patient responds to a treatment but another does not.”
An outlook for the future
Proof-of-concept microfluidic devices are potentially revolutionary with wide ranging positive impacts for industry and society, however, there remains a disconnect between the increasing number of research efforts and the lack of sufficient early-stage investment to help get these products to market. While a growing number of microfluidic devices are being commercially developed by startups, unfortunately many innovations will never make it out of the research lab to the clinic. “It would be great if a larger ecosystem could be built to support this transition from the lab to the clinic. With this in place, we would be more likely to bridge the gap and ensure patients benefit from this type of technological evolution,” emphasizes Libbrecht.
Once again, it seems the solution lies in collaboration.
