Magnetic tweezers | EPFL Graph Search

Magnetic tweezers (MT) are scientific instruments for the manipulation and characterization of biomolecules or polymers. These apparatus exert forces and torques to individual molecules or groups of molecules. It can be used to measure the tensile strength or the force generated by molecules. Most commonly magnetic tweezers are used to study mechanical properties of biological macromolecules like DNA or proteins in single-molecule experiments. Other applications are the rheology of soft matter, and studies of force-regulated processes in living cells. Forces are typically on the order of pico- to nanonewtons (pN to nN). Due to their simple architecture, magnetic tweezers are a popular biophysical tool. In experiments, the molecule of interest is attached to a magnetic microparticle. The magnetic tweezer is equipped with magnets that are used to manipulate the magnetic particles whose position is measured with the help of video microscopy. Construction principle and physics of ma

Automated microfluidic sorting of mammalian cells labeled with magnetic microparticles for those that efficiently express and secrete a protein of interest

Niamh Harraghy, Etienne Lançon, Nicolas Mermod, Amar Rida

We developed a method for the fast sorting and selection of mammalian cells expressing and secreting a protein at high levels. This procedure relies on cell capture using an automated microfluidic device handling antibody-coupled magnetic microparticles and on a timed release of the cells from the microparticles after capture. Using clinically compatible materials and procedures, we show that this approach is able to discriminate between cells that truly secrete high amounts of a protein from those that just display it at high levels on their surface without properly releasing it. When coupled to a cell colony imaging and picking device, this approach allowed the identification of CHO cell clones secreting a therapeutic protein at high levels that were not achievable without the cell sorting procedure. Biotechnol. Bioeng. 2017;114: 1791-1802. (c) 2017 Wiley Periodicals, Inc.

Wiley2017

Separation of magnetic microparticles in segmented flow using asymmetric splitting regimes

Matteo Cornaglia, Martinus Gijs

A magnetic microparticle-based bioassay requires the separation of the microparticles from the sample matrix, after the microparticles have specifically captured the target of interest. For the implementation of such an assay in water-in-oil droplet segmented flow microfluidics, the particles must be separated from the aqueous sample droplets during a purification step. Current magnetic separation methods pose limits to purification, as only a limited part of the sample volume is removed in the purification step. Combining asymmetric droplet splitting in a T-junction-shaped microfluidic channel with magnetic separation, as induced by a permanent magnet positioned close to the microfluidic channel, is a promising and elegant solution for extracting the magnetic microparticles. However, retaining a high separation efficiency is a challenge and yet untried. In this paper, we describe a microfluidic and magnetic setup to separate superparamagnetic microparticles from the sample droplets, removing up to 90 % of the original sample volume in a single purification step, while keeping the separation efficiency constant. First, the conditions for particle aggregation, attraction and immobilization are determined and used to predict good separation conditions. Second, the magnetic forces at the splitting zone on the microfluidic chip are simulated for different permanent magnet positions and orientations; hereafter, the most promising setups are experimentally realized in polydimethylsiloxane microchannels, tested and the results considering different splitting regimes compared.

Springer Heidelberg2015

Microdevices for Locomotion in Complex Biological Fluids

Tian Qiu

Locomotion is an essential feature for survival of many organisms, and it is also a technical requirement for untethered biomedical microdevices to operate inside the human body for targeted drug delivery and minimally invasive surgery. The overall goal of this thesis is to develop microdevices that are capable of actively propelling themselves through and performing tasks in complex biological fluids. Two major challenges are encountered: the complex fluidic environment and the small length scale. The first part of the thesis addresses the first challenge: the diverse rheological properties of biological fluids. Most biological fluids are non-Newtonian, and to move in these fluids, the propulsion scheme is highly dependent on the size of the device: 1) When it is comparable or smaller than the mesh size of the biopolymeric network, then the device experiences purely viscous drag, thus the schemes for propulsion in Newtonian fluids will still be effective. To study the active microrheology of porous biological fluids, a magnetic tweezer set-up is constructed to pull magnetic beads of varying size through the porcine vitreous. It is found that for unhindered propulsion through the vitreous, nanodevices with a cross-section of less than 500 nm are needed. 2) When the size of the device is larger than the fluidic mesh size, non-Newtonian properties of the fluid become important and can be utilized for propulsion. We design the first symmetric micro-swimmer actuated by reciprocal motion and demonstrate its propulsion in biologically-relevant fluids. A larger scale low Reynolds number swimmer model is also built and excellent agreement between measurements and theory indicates that the net propulsion is caused by modulation of the fluid viscosity upon varying the shear rate. It opens new possibilities of using a simple actuation scheme for propulsion in non-Newtonian biological fluids. The second challenge is the small size of the device which severely limits the choice of available miniaturized actuators. We explore a novel wireless ultrasonic actuation scheme and a prototype is tested for application in the urinary tract. In order to test the prototype, a general technique is first developed to build a phantom of the human kidney. Based on high resolution medical imaging data, a three dimensional (3D) model is constructed using 3D printing and polymer casting techniques. The phantom not only faithfully reproduces the anatomical structural details, but also mimics the mechanical properties of the real tissue. To address the challenge of powering untethered microdevices, a novel bubble array streaming surface (BASS) actuator is developed. Under ultrasonic excitation, the oscillation of micro gas bubbles results in acoustic streaming and provides a propulsive force that drives the device. Ultrasonic actuators with different bubble sizes are fabricated, and individual driving frequency and propulsive force are measured. The actuator operates as an end-effector of a miniaturized endoscope, which has a cross-sectional side length of only 1 mm, thinner than the endoscopes currently in use. The tip of the end-effector is equipped with a miniaturized camera, its orientation is controlled wirelessly by the actuator, and active cystoscopy is successfully performed inside a rabbit bladder. Miniaturized medical instruments and micro-robots will benefit from the wireless actuation schemes demonstrated herein.

EPFL2016

Microdevices for Locomotion in Complex Biological Fluids

Tian Qiu

EPFL2016