Pushing the boundaries of acoustic particle separation: achieving high-throughput, avoiding spillover effects, investigating the effects of the particle concentration, and measuring acoustic properties
(2022) BMEM01 20221Department of Biomedical Engineering
- Abstract
- Acoustophoresis, i.e., the contactless manipulation of small cells or particles via acoustic waves is a gentle and label-free method that can, amongst others, be used to isolate rare cells such as circulating tumor cells from blood. To isolate enough cells, a large amount of sample needs to be processed in a reasonable amount of time. In a clinical setting, usually around 10 mL of blood can be collected from a patient. Typically, a throughput higher than 100 µL/min is expected to process the whole sample under one hour. Currently, the sample throughput achievable by acoustophoresis is around 5 to 20 µL/min. The underlying work aims at resolving this exact challenge. Several different strategies exist to increase the throughput. First,... (More)
- Acoustophoresis, i.e., the contactless manipulation of small cells or particles via acoustic waves is a gentle and label-free method that can, amongst others, be used to isolate rare cells such as circulating tumor cells from blood. To isolate enough cells, a large amount of sample needs to be processed in a reasonable amount of time. In a clinical setting, usually around 10 mL of blood can be collected from a patient. Typically, a throughput higher than 100 µL/min is expected to process the whole sample under one hour. Currently, the sample throughput achievable by acoustophoresis is around 5 to 20 µL/min. The underlying work aims at resolving this exact challenge. Several different strategies exist to increase the throughput. First, increasing the total flow rate or the sample flow rate are obvious candidates. However, at high flow rates inertia effects impact the flow dynamics and the spillover effect occurs, which pushes all particles in the center outlet and thus, renders all separation impossible. Herein, we show that the spillover effect can be reduced by tuning the outlet splitting ratio. We obtain separation with an unprecedented sample throughput of 1200 µL/min. A second strategy consists of analyzing the set up numerically, to find the optimal setting parameters in silico. To this aim, we set up a finite element model and validated it with experimental results. To our surprise, the position of the streamlines in the prefocusing channel depends on the prefocusing voltage at high flow rates, which raises new questions on the behavior of the chip at these flow conditions. By considering this effect in the finite element model, simulations and experiments give similar positions of the particle streamline in the main channel. A third strategy to increase throughput is to run the separation at high sample concentrations. However, this entails that the particles are closer to each other, which can lead to hydrodynamic particle-particle interactions. We made a few observations at high particle concentrations. An increase in apparent acoustic energy density was observed. Furthermore, the separation curve, which is used as a tool to characterize particle separations, showed that increasing the concentration or the flow rates hinders particle separation. Here, another surprising effect occurred: at very high flow rates, and rather high inlet splitting ratios, the gap between the two particle streamlines is much larger than what we would expect from the theory. This effect could be further investigated to improve the separation performance. Finally, we introduce a new method to measure the mobility ratio of cells and particles based on particle separation. The method is validated by measurements previously obtained with particle tracking. The advantage of particle separation with respect to particle tracking is that many particles can be evaluated at once. Moreover, it does not require any knowledge on the flow rate, the acoustic energy density, the viscosity of the fluid, or the length of the channel. (Less)
- Popular Abstract
- Expanding our knowledge on particle separation using acoustic waves to improve its throughput
Microfluidics is the use of small channels to control small volumes of fluids. At the microscale, the fluid behaviour is predictable which is an advantage when you want a precise control of the fluids. Acoustophoresis means the use of sound waves to handle cells and particles in a microfluidic channel. With acoustophoresis we can separate a cell type from another based on their properties such as density or compressibility. We exploit channel resonance by placing transducers on the channel wall. We build up a strong acoustic field that results in lateral forces. The forces induce motion and the speed of the particle depends on its mechanical... (More) - Expanding our knowledge on particle separation using acoustic waves to improve its throughput
Microfluidics is the use of small channels to control small volumes of fluids. At the microscale, the fluid behaviour is predictable which is an advantage when you want a precise control of the fluids. Acoustophoresis means the use of sound waves to handle cells and particles in a microfluidic channel. With acoustophoresis we can separate a cell type from another based on their properties such as density or compressibility. We exploit channel resonance by placing transducers on the channel wall. We build up a strong acoustic field that results in lateral forces. The forces induce motion and the speed of the particle depends on its mechanical properties. Thus, it is possible to separate slow particles from fast particles. The fastest particles or cells will move closer to the center of the channel. By placing two outlets, one in the center of the channel, one on the sides, the particles will be separated by exiting through different outlets. An application of such system is to isolate rare cells. Only one to ten circulating tumor cells (CTCs) can be found in one milliliter of blood from a patient with metastatic disease. In comparison, there are millions of white blood cells and billions of red blood cells in one milliliter of blood. To isolate the CTCs, a large volume of sample needs to be processed. The throughput of the chip needs to be improved to have the sample processed in a reasonable amount of time, which means minutes, not hours. A logical step to increase the throughput is to increase the total flow rate. However, increasing the flow rate induces the spillover effect, all the particles exit through the center outlet and particle separation is impossible. By changing the flow rate ratios we succeeded to reduce the spillover effect and separation was obtained at a high flow rate of 1200 µL/min. In some applications, the sample is diluted before processing which impacts the throughput of the chip. Separation needs to be achievable even at high concentration to not have to dilute the sample. When concentration is higher, particles are closer to each other and are more likely to interact with each others. The inter-particle interaction leads to hydrodynamic forces which deflect the particles trajectories. Indeed, we showed that for higher concentrations the particles are more focused towards the center of the channel. Depending on their difference in acoustic properties, some cells or particles will be separated from each other more easily than others. In order to quantify this difference of mobility, we use the mobility ratio. It can be measured using methods such as particle tracking, but this method is time consuming and analyses the cells individually. By using particle separation, we tested a new and faster method to measure the mobility ratio which gives similar results to particle tracking. The thesis presents new leads on how to improve particle separation and highlights the limitations that can be encountered when processing at high throughput. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9098122
- author
- Péroux, Linda LU
- supervisor
- organization
- course
- BMEM01 20221
- year
- 2022
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- additional info
- 2022-17
- id
- 9098122
- date added to LUP
- 2022-09-05 15:51:30
- date last changed
- 2022-09-05 15:51:38
@misc{9098122,
abstract = {{Acoustophoresis, i.e., the contactless manipulation of small cells or particles via acoustic waves is a gentle and label-free method that can, amongst others, be used to isolate rare cells such as circulating tumor cells from blood. To isolate enough cells, a large amount of sample needs to be processed in a reasonable amount of time. In a clinical setting, usually around 10 mL of blood can be collected from a patient. Typically, a throughput higher than 100 µL/min is expected to process the whole sample under one hour. Currently, the sample throughput achievable by acoustophoresis is around 5 to 20 µL/min. The underlying work aims at resolving this exact challenge. Several different strategies exist to increase the throughput. First, increasing the total flow rate or the sample flow rate are obvious candidates. However, at high flow rates inertia effects impact the flow dynamics and the spillover effect occurs, which pushes all particles in the center outlet and thus, renders all separation impossible. Herein, we show that the spillover effect can be reduced by tuning the outlet splitting ratio. We obtain separation with an unprecedented sample throughput of 1200 µL/min. A second strategy consists of analyzing the set up numerically, to find the optimal setting parameters in silico. To this aim, we set up a finite element model and validated it with experimental results. To our surprise, the position of the streamlines in the prefocusing channel depends on the prefocusing voltage at high flow rates, which raises new questions on the behavior of the chip at these flow conditions. By considering this effect in the finite element model, simulations and experiments give similar positions of the particle streamline in the main channel. A third strategy to increase throughput is to run the separation at high sample concentrations. However, this entails that the particles are closer to each other, which can lead to hydrodynamic particle-particle interactions. We made a few observations at high particle concentrations. An increase in apparent acoustic energy density was observed. Furthermore, the separation curve, which is used as a tool to characterize particle separations, showed that increasing the concentration or the flow rates hinders particle separation. Here, another surprising effect occurred: at very high flow rates, and rather high inlet splitting ratios, the gap between the two particle streamlines is much larger than what we would expect from the theory. This effect could be further investigated to improve the separation performance. Finally, we introduce a new method to measure the mobility ratio of cells and particles based on particle separation. The method is validated by measurements previously obtained with particle tracking. The advantage of particle separation with respect to particle tracking is that many particles can be evaluated at once. Moreover, it does not require any knowledge on the flow rate, the acoustic energy density, the viscosity of the fluid, or the length of the channel.}},
author = {{Péroux, Linda}},
language = {{eng}},
note = {{Student Paper}},
title = {{Pushing the boundaries of acoustic particle separation: achieving high-throughput, avoiding spillover effects, investigating the effects of the particle concentration, and measuring acoustic properties}},
year = {{2022}},
}