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The slow are the fastest: a new method for separating molecules and biological particles in tiny samples

Joint development of scientists at the Technion and IBM laboratories in Switzerland: a device that separates biological particles according to their size using an electric field. The device may be used in rapid diagnosis of corona patients

Members of the joint Technion and IBM research team: in the photos: Prof. Moran Berkowitz, Dr. Federico Pretora, Vesna Bacheva, Dr. Govind Gaikla
Members of the joint Technion and IBM research team: in the photos: Prof. Moran Berkowitz, Dr. Federico Pretora, Vesna Bacheva, Dr. Govind Gaikla

Joint research by researchers from the Technion and IBM laboratories in Zurich led to the development of a new method for separating particles and molecules from small samples. The device may help in the rapid analysis of samples from corona patients, under a grant from the Innovation Authority.

In an article published by the researchers in the journal Angewandte Chemie, they present a new method for separating biological particles and molecules from a liquid. This development was defined by one of the article's reviewers as "a huge contribution to the field and a breakthrough the likes of which only happens once every decade or two."

This is a tiny device that quickly separates different types of particles: small particles stay near the entrance to the device, while large particles quickly move away from the opening. The group calls the new method BFF, short for bidirectional flow filter. The article presents a theoretical analysis of the system, its experimental verification and guidelines for the design of future devices for different uses. The research group at the Technion was led by Prof. Moran Berkovich from the faculties of mechanical engineering and biomedical engineering, head of the laboratory for microflow technologies.

The device presented by the researchers in the article is a microfluidic chip in which the liquid sample is separated into its components by flowing through virtual channels through electro-osmosis - control of liquid flow by electric fields and surface charge. In the current study, the researchers used this technology to create a two-way flow - the flow of the liquid in two opposite directions at the same time. The traditional approach - controlling the flow using pumps, valves and channels - does not allow to achieve such flow patterns.

A video explaining the research

In the new device, when particles are injected into the flow field, they behave in a well-explained but surprising way: small particles stay in place, while large particles are transported quickly. According to doctoral student Vanessa Bacheva from the Technion, one of the two main authors of the article, "Particles in liquid and gas move randomly - a phenomenon called Brownian motion. This movement leads to the fact that particles in the gas tend to disperse in space so that they will eventually be uniformly dispersed in it. This is the mechanism thanks to which we can smell, after a certain time, a bottle of perfume that is opened on the other side of the room - because the molecules move randomly and disperse in space in a process also called diffusion."

Diffusion processes are characterized by the correlation between the size of the particle and its level of diffusivity - small particles are more diffusive than large particles. In the innovative device developed by Prof. Berkovich's research group, a two-way flow takes place, and the result is that the large particles in the sample, which are characterized by low diffusivity, drift with the current, while the small particles run quickly between the opposite current lines and therefore experience zero velocity on average and remain close to the entrance to the cell the flow. The result is a tiny device that separates particles according to their size.

"The principle here is quite simple," says Dr. Federico Pretora, a postdoctoral student working at IBM laboratories in Zurich, also lead author of the paper. "Surprisingly, this is something that has not been done until now, probably due to technological limitations. We managed to overcome these limitations through continuous research that included many trials and improvements, and the result is a solid standard that can be produced commercially for the benefit of new diagnostic tools and as a basis for new research tools of tiny samples."

Professor Moran Berkovich explains that "most devices for biological diagnosis are based on the creation of a reaction between sensing molecules (probes) and the target molecules or particles that are being sought, followed by the removal of the sensing molecules that have not bound to the target. This process, especially in the last step, is very complicated to implement especially when it comes to in small samples. Our method does this quickly and efficiently, as long as the sensing and target molecules are sufficiently different from each other."

Now the team is working on adapting the method for rapid monitoring of the SARS-CoV-2 virus based on a sample from the throat surface. Dr. Govind Gaikla from IBM explains that "Fortunately, viruses are relatively large - their diameter is about 100 nanometers, much larger than antibodies or other sensing molecules that we use. Our idea is to put the sample into our flow cell, where the viruses will meet luminescent sensing molecules that will stick to them, and only the labeled viruses will flow out while the excess sensing molecules will be left behind."

The research was funded by a MetamorphChip grant from the European Research Commission (ERC) and the BRIDGE program funded by the Swiss Innovation Authority (Innosuisse) and the Swiss Science Foundation (SNF).

for the scientific article

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