Physics of microfluidics to predict the outcome of cancer therapies

One of the great challenges in the fight against cancer is to design new technologies for personalized treatment for each patient. Depending on the molecular characteristics —DNA mutations and others— of each tumor, precision medicine wants to make it easier for cancer patients, both adults and children, to receive personalized treatment appropriate to their pathology. But, is it possible to know if a patient can benefit or not from a treatment before starting the therapy?

A team of experts from the Faculty of Medicine and Health Sciences of the University of Barcelona (UB) and the Institute of Bioengineering of Catalonia (IBEC) have designed a microfluidic device called Microfluidic Dynamic BH3 Profiling (μDBP) that predicts the efficacy of cancer treatment quickly and automatically, using a reduced amount of cells from biopsies and without requiring specialized technical personnel.

The work was directed by Joan Montero, professor in the Department of Biomedicine of the UB and IBEC, and Javier Ramón-Azcón, ICREA research professor at IBEC. In the study, whose first author is Albert Manzano (UB-IBEC) —PhD at the UB in 2022 with a thesis on precision medicine in the fight against cancer—, experts from the Faculty of Physics of the UB also participate , the Vall d’Hebron Institute of Oncology (VHIO) and the Center for Biomedical Research Network Bioengineering, Biomaterials and Nanomedicine (CIBERBBN) consortium, in Spain.

Precision medicine in the fight against cancer

Personalized medicine has revolutionized the way of designing increasingly effective cancer treatments. If we consider that each tumor is unique and has its own characteristics, having predictive indicators of each patient’s response to treatment is a great step forward in oncology. DBP (dynamic BH3 profiling) was initially developed in the laboratory of Professor Anthony Letai —Professor Montero was a co-inventor— and patented in 2015 by the Dana-Farber Cancer Institute (United States). It was one of the first functional assays successfully tested to predict treatment in various types of cancer. This system puts cancer cells in contact with different therapeutic options to quickly identify ex vivo those that could be most effective in eliminating the tumor. Conceptually, it is very similar to antibiograms used in the identification of antibiotics to treat bacterial infections.

“DBP has been used to identify the efficacy of treatments on a preclinical and clinical scale in many different types of cancer, both solid and liquid. These studies have used cell lines, animal models and primary samples with great predictive capacity in all cases. However, this assay has not yet been widely applied in hospitals”, explains Professor Joan Montero.

“So far,” he adds, “several studies have found a good correlation between the results of the DBP and the clinical response in primary samples of leukemia. There are currently several open clinical trials, with which we hope that this technology can be implemented in hospitals in the coming years to improve cancer therapies.”

Predict therapeutic response with few cancer cells

Now, the new DBP-type microfluidic device —known as μDBP— solves several challenges of functional assays: it reduces the number of cancer cells needed to test possible therapies ex vivo and automates the process to facilitate its clinical application without specialized technical personnel.

“One of the main limitations of DBP is the number of cells needed to carry out the assay. When a patient is biopsied, the number of tumor cells obtained is very limited, which does not allow a study with many different treatments and limits the ability to identify one that is effective,” explains expert Albert Manzano.

The experts Albert Manzano and Joan Montero at the Faculty of Medicine and Health Sciences of the UB. (Photo: UB)

When a biopsy is received, the sample is dissociated to obtain individual cells using mechanical and enzymatic treatment. Once processed, the sample is filtered to obtain individual cells that will then be subjected to the desired treatments and seeded in the microfluidic device.

“Thanks to our μDBP microfluidic platform, which is equipped with small wells to seed the cells, we can reduce the number of cells required to test a treatment. This is a decisive innovation to increase the number of drugs that can be evaluated”, adds Manzano.

A fast and fully automated system

The new research and development work is the first in which microfluidics is applied to carry out the functional assay of DBP. Unlike other versions developed up to now, such as the high-throughput DBP (Bhola et al., Science Signaling, 2020) with plates and automatic dispensers to test hundreds of treatments, the new μDBP device is aimed at testing treatments in situ in a very fast (which prevents the deterioration of the samples), simple and automated, without the need for expensive machinery or specialized personnel.

“The biggest advantage of the μDBP device is also the automation of the entire process, which would help to implement this functional methodology on a clinical scale. Taken together, all these advantages would facilitate the adoption of the DBP system in hospitals as a routine test”, the experts detail.

“We have developed this new tool with the idea of ​​making it available to oncologists. This automated system makes it possible to obtain personalized information about the patient and the treatment”, explains Javier Ramón-Azcón (IBEC).

As the team details: “We will continue to work with our clinical partners to analyze patient samples and adapt this methodology to improve personalized treatment of multiple cancers for the benefit of all cancer patients.”

The research and development team discusses the technical details of the new device in the academic journal npj Precision Oncology, under the title “Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy”. (Source: UB)