HPIM – High Precision Inertial Microfluidics at High Pressures
2021 - 2023
- Dept Materials Science and Engineering, Uppsala University
- Dept Protein Science, KTH
Klas Hjort, Microsystems Technology, Uppsala University
Aman Russom, Nanobiotechnology, KTH
Javier Cruz, both organisations
Inertial focusing is a phenomenon where initially randomly distributed particles are focused in well-defined positions as they travel through a microfluidic system. The movement across the main flow is attributed to a force (lifting force) that is applied to the particles due to their interaction with the liquid as they travel through the microchannels. The force originates in originates in the transfer of momentum from the fluid to the particles, which only occurs in systems where inertia plays a role. In fact, the phenomenon was first observed by Segré & Silbeberg in 1961, but the analytical models commonly used for calculations in flowing microsystems, where inertia is neglected, failed to explain the experimentally observed behaviour of the particles. It was not until 1974 that Ho & Leal gave an analytical explanation for the phenomenon, which is today accepted as the basis for our understanding of the phenomenon.
We use high pressures (up to 200 bar) for the first time to enable focusing, separation and concentration of bacteria with high throughput. This new technology not only achieves excellent performance for focusing and concentrating particles, but it can provide an extreme resolution when separating the particles according to their size (mathematically unlimited; demonstrated experimentally for differences in size down to 80 nm). It is perhaps even more important that the systems are stable, predictable and easy to design - properties that we hope will make the technology with its outstanding advantages more accessible to a larger community than those currently researching in the field.
The birth of microsystems offered technical solutions that were not previously possible, as it is not only the smallness that characterizes the microsystems but also the unique phenomena that occur when they become small enough. Such a unique phenomenon, inertia focusing, can be created in flowing microsystems with a laminar flow (we describe it a little further down) when the inertia of a particle is important. Inertial focusing enables different types of manipulation of particles in liquid samples, such as focusing, separation and concentration, and even transfer to another liquid, thereby facilitating their detection and analysis..
These abilities are the key to a difficult-to-solve problem: analysis of complex fluid samples, where rare particles of interest may be present in a very small number among a huge number of others, making the analysis difficult - if not impossible. Examples of interesting rare particles in complex fluids are circulating tumour cells in blood that provide important information about cancer, extracellular vesicles in blood that contain biomarkers with physiological and pathological information, or bacteria and algae in water, where the species and its number may need to be monitored for biological studies or for safety reasons.
Given these interesting complex samples, how can the most advanced sensors of the XXI century detect and analyse a particle surrounded by millions or billions of others in a matrix full of molecules? The answer is very simple. They cannot. Even the most sensitive and selective sensor struggles in such an environment. When we seek for more advanced information, a stand-alone sensor is not enough, it requires several other integrated components to help it, for sample preparation, transport of the sample and a controlled environment (e.g. temperature or pH). Today, this is usually performed by several different instruments in a laboratory. With the help of its small size, a flowing microsystem can offer a complete laboratory on a small surface, a lab on a chip (where the chip connects to the microelectronics chip with processors, memories or other advanced integrated circuits). It can offer great benefits in cost for both the system and its use, as well as less need for sample materials and expensive analytical fluids.
When choosing a technique for studying rare particles, generally high throughput is needed to extract them from the sample. It is like finding a very small needle in a small haystack. A passive technology enables this at the same time, as it is simple and robust because the process simply consists of passing the sample through the flow system at a controlled speed. In addition, passive techniques are label-free, which reduces the complexity and costs of the process and offers sorting of unknown particles. By comparison, active techniques can provide more flexibility, as the force can be adjusted externally; and labelling techniques can usually offer higher specificity. Depending on the application, different techniques are needed to prepare a sample. We started this project because it was clear that a new technology was needed to offer high throughput sample preparation of rare extremely small particles such as bacteria, viruses and organelles of eukaryotic cells.
With its remarkably good performance, it would come as no surprise that inertial focus in the near future may change the way analyses are performed and open up opportunities beyond what is possible today.