Magnetic actuation of microparticles for mass transfer enhancement

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The motion of magnetic microparticles (250μm diameter) in a circular microfluidic reactor with a diameter of 10 mm under time dependent magnetic field has been studied using CFD code COMSOL. The effect of actuation protocol on the local and average particle velocity has been investigated. The local Sh numbers were obtained as a function of angular particle position in the range of Re numbers between 0.05 and 10 while the particle velocity was changed over two orders of magnitude. Under time dependent magnetic field, the thickness of the boundary layer continuously changes which results in an increased mass transfer towards the particle surface under periodic particle velocity conditions as compared to steady state velocity conditions. A good agreement between numerical and experimental data has been observed

Optimization of magnetic actuation protocol to enhance mass transfer in solid/liquid microfluidic systems

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The dynamic properties of a 250 m magnetic microparticle in a time varying magnetic field have been studied in a PDMS microreactor with a diameter of 13 mm using a dual coupled quadrupolar arrangement of electromagnets. A sinusoidal applied magnetic field has dictated a circular motion of the particles in the microreactor in the frequency range below 0.6 Hz. Different circular motion modes have been observed at higher frequencies of the applied field. The particular symmetric arrangement of the magnets has allowed a non-steady-state motion with variation in velocity between magnetic poles. The motion of magnetic particle has been described in terms of average velocity and mean square deviation from average velocity. The effect of actuation protocol parameters (frequency, magnetic field strength and phase shift) on particle velocity and acceleration has been investigated. The maximum average velocity of 0.016 m/s has been observed under an optimized actuation protocol. The mass transfer rate towards the particle surface is mainly influenced by the average velocity while the effect of acceleration/deceleration of the particle has an order of magnitude less influence

Parallel manipulation of individual magnetic microbeads for lab-on-a-chip applications

Many scientists and engineers are turning to lab-on-a-chip systems for cheaper and high throughput analysis of chemical reactions and biomolecular interactions. In this work, we developed several lab-on-a-chip modules based on novel manipulations of individual microbeads inside microchannels. The first manipulation method employs arrays of soft ferromagnetic patterns fabricated inside a microfluidic channel and subjected to an external rotating magnetic field. We demonstrated that the system can be used to assemble individual beads (1-3µm) from a flow of suspended beads into a regular array on the chip, hence improving the integrated electrochemical detection of biomolecules bound to the bead surface. In addition, the microbeads can follow the external magnet rotating at very high speeds and simultaneously orbit around individual soft magnets on the chip. We employed this manipulation mode for efficient sample mixing in continuous microflow. Furthermore, we discovered a simple but effective way of transporting the microbeads on-chip in the rotating field. Selective transport of microbeads with different size was also realized, providing a platform for effective sample separation on a chip. The second manipulation method integrates magnetic and dielectrophoretic manipulations of the same microbeads. The device combines tapered conducting wires and fingered electrodes to generate desirable magnetic and electric fields, respectively. By externally programming the magnetic attraction and dielectrophoretic repulsion forces, out-of-plane oscillation of the microbeads across the channel height was realized. Furthermore, we demonstrated the tweezing of microbeads in liquid with high spatial resolutions by fine-tuning the net force from magnetic attraction and dielectrophoretic repulsion of the beads. The high-resolution control of the out-of-plane motion of the microbeads has led to the invention of massively parallel biomolecular tweezers.Ph.D.Committee Chair: Hesketh, Peter; Committee Member: Allen, Mark; Committee Member: Degertekin, Levent; Committee Member: Lu, Hang; Committee Member: Yoda, Minam

Magnetic actuation of microparticles for mass transfer enhancement

The motion of magnetic microparticles (250μm diameter) in a circular microfluidic reactor with a diameter of 10 mm under time dependent magnetic field has been studied using CFD code COMSOL. The effect of actuation protocol on the local and average particle velocity has been investigated. The local Sh numbers were obtained as a function of angular particle position in the range of Re numbers between 0.05 and 10 while the particle velocity was changed over two orders of magnitude. Under time dependent magnetic field, the thickness of the boundary layer continuously changes which results in an increased mass transfer towards the particle surface under periodic particle velocity conditions as compared to steady state velocity conditions. A good agreement between numerical and experimental data has been observed

Magnetic particle actuation for functional biosensors

Molecular processes play a major role in the biology of the human body. As a consequence, molecular-level information can be very effctively used for medical diagnostics. In medical practice, samples of e.g. blood, urine, saliva, sputum, faeces or tissue are taken and investigated in specialized laboratories using a variety of biological tests. The tests can generally be separated into five process steps: (i) sample taking, (ii) sample preparation, (iii) specific recognition of the molecules of interest, (iv) transduction of the presence of the molecules into a measurable signal and (v) translation of the measured signal into a diagnostic parameter that can support the treatment of the patient. Particles with nanometer to micrometer sizes are widely used as carriers and labels in bio-analytical systems/assays. An important class of particles used in in-vitro diagnostics are so-called super-paramagnetic particles, which consist of magnetic nanoparticles embedded inside a non-magnetic matrix. The absence of magnetic material in biological samples allows a controlled application of magnetic fields. Super-paramagnetic particles are therefore powerful because they can be easily manipulated and reliably detected inside complex biological fluids. These properties are exploited in magnetic-label biosensors, which employ the magnetic particles as labels in order to measure the concentration of target molecules in a biological sample.In this thesis we investigate techniques for a novel generation of biosensors - called functional biosensors - in which the concentration as well as a functional property of biological molecules can be determined by controlled manipulation of the magnetic particles. We demonstrate real-time on-chip detection and manipulation of single super-paramagnetic particles in solution. The chip-based sensor contains micro fabricated on-chip current wires and giant magneto resistance (GMR) sensors. The current wires serve to apply force on the particles as well as to magnetize the particles for on-chip detection. By simultaneously measuring the sensor signal and the position of an individual particle crossing the sensor, the sensitivity profile of the sensor was reconstructed and qualitatively understood from a single-dipole model. The manipulation of multiple particles in parallel combined with real-time detection of single particles opens the possibility to perform on-chip high-parallel assays with single-particle resolution. The drawback of on-chip magnetic actuation and detection is the limited amount of statistics since only a limited amount of particles (typically several dozens) can be used in a single experiment. To study a large number of particles (typically several hundreds) without hydrodynamic and magnetic particle-to-particle interactions, a magnetic tweezers setup is designed and built to apply translational pulling forces to magnetic particles. The magnetic tweezers setup is based on an electromagnet combined with an optical microscope for the detection of the particles. Using this setup the non-specific binding of protein coated particles to a glass substrate is measured for various buffer conditions. The increase of binding with increasing ionic strength is understood from the electrostatic interaction between the particles and the glass substrate. A complementary way to probe biological molecules or interactions is by applying a controlled torsion, i.e. a controlled rotation under well-defined torque. Particle based single-molecule experiments described in literature already indicate novel types of assays enabled by the application of rotation to biological molecules. Although the degree of rotation was known in these single-molecule experiments, the quantitative value of the applied torque was not controlled. In fact, it is a surprise that a torque can be applied because in an idealized super-paramagnetic particle, the angle difference between the induced magnetization and the applied magnetic field is zero and thus the torque should be zero as well. To answer the question which physical mechanism is responsible for torque generation, a rotating magnetic field was applied to single super-paramagnetic particles by on-chip current wires. We unraveled the mechanisms of torque generation by a comprehensive set of experiments at different field strengths and frequencies, including field frequencies many orders of magnitude higher than the particle rotation frequency. A quantitative model is developed which shows that at field frequencies below 10 Hz, the torque is due to a permanent magnetic moment in the particle of the order of 10¡15 Am2. At high frequencies (kHz - MHz), the torque results from a phase lag between the applied field and the induced magnetic moment, caused by the non-zero relaxation time of magnetic nanoparticles in the particle. A magnetic quadrupole setup is developed to upscale the rotation experiments to multiple particles in parallel. The advantage of the rotation experiments over the pulling experiments is that rotation experiments not only give information on dissociation but also on association processes. Using the quadrupole setup, the non-specific binding between protein coated particles and a glass substrate is measured for various buffer conditions. The increase of binding with increasing ionic strength and decreasing pH is understood from the electrostatic interaction between the particles and the glass substrate. When coating the glass substrate with bovine serum albumin (BSA), the non-specific binding of streptavidin coated particles is strongly reduced. Although the blocking effect of BSA is not fully understood, our measurements clearly show the feasibility of rotational excitation of particles to probe molecular interactions. Finally, we studied the feasibility of rotational actuation of magnetic particles to measure the torsional stiffness of a biological system with a length scale of several tens of nanometers. As a model system we used protein G on the particles that binds selectively to the crystallisable part of the IgG antibody that is physically adsorbed on a polystyrene substrate. The angular orientation of the particles that are bound to the substrate show an oscillating behavior upon applying a rotating magnetic field. The amplitude of this oscillation decreases with increasing anti-body concentration, which we attribute to the formation of multiple bonds between the particle and the substrate. By evaluating the details of the oscillatory behavior, we found a lower limit of the torsional modulus of the IgG-protein G complex of 6¢10¡26 Nm2. The torsional modulus is two orders of magnitude larger than typical values found in literature for DNA strands. A difference in torsional modulus is expected from the structural properties of the molecules i.e. DNA is a long and flexible chain-like molecule whereas the protein G and IgG molecules are more globular due to the folding of the molecule

Roadmap for optical tweezers

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects, ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in the life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nano-particle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration.journal articl

Roadmap for optical tweezers

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMOptical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects, ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in the life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nano-particle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space explorationEuropean Commission (Horizon 2020, Project No. 812780

Roadmap for Optical Tweezers 2023

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nanoparticle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration

ACTIVE MANIPULATION OF EXTRACELLULAR MATRIX STIFFNESS

Ph.DDOCTOR OF PHILOSOPH

Dynamics of individual magnetic particles near a biosensor surface

The use of magnetic particles in biosensing is advantageous for transport of target molecules in the device, for assay integration, and for labeled detection. The particles generally have a size between 100 nm and 3 ¿m and are of a superparamagnetic nature, being composed of thousands of iron oxide grains in a polymer matrix. In this thesis we describe a series of detailed microscopy studies of magnetic particles near to and coupled to a biosensor surface, in order to characterize their dynamic behavior and their magnetic properties. The first part of the thesis deals with the use of integrated microscopic current wires to study and manipulate unbound particles on a chip surface. The magnetic properties of individual particles are characterized in magnetic fields below 10 mT using on-chip magnetophoretic analysis and on-chip Brownian motion analysis. In magnetophoretic analysis, the volume susceptibility of 1 µm particles is determined by optically measuring the speed of particles moving between two current wires. The analysis reveals distinct differences in volume susceptibilities of particles with the same outer diameter. In addition to DC magnetic fields, also AC magnetic fields are applied, showing a decrease in particle susceptibility for increasing field frequencies. To reduce the hydrodynamic perturbation by the surface in on-chip magnetophoretic analysis, we present a chip design in which a particle can move back and forth in the channel between two large wires. In Brownian motion analysis, small particles of 150 to 450 nm are trapped in a tunable magnetic potential well above an integrated current wire. The histogram of two-dimensional particle positions reveals the strength of the particle magnetization. Using straight current wires, we demonstrate differences in bead susceptibility of an order of magnitude and differences in volume susceptibility of more than a factor of two. By using wires with surface barriers and wires with a tapered shape, the accuracy of the susceptibility determination is improved to better than 10%. We also show that combining a tapered wire with an external uniform field can give additional information on particle properties such as anisotropy or a small permanent magnetic moment. The second part of the thesis describes a study of the dynamics of particles that are biologically bound to a sensor surface. We show that an optical eva-nescent field can be used to study the thermal out-of-plane motion of bound particles with nanometer resolution, because the scattered light intensity of the particles depends on the height above the surface. By using a biological tether of known length (dsDNA of 290 bp/99 nm) we show that height variations can be quantitatively determined. We demonstrate that the accuracy of the height determination depends on the properties of the used particles, e.g. the shape, smoothness, and internal structure. Optimal results are found for polystyrene particles and magnetic particles that are smooth and spherical. Next, we show that the bond between a particle and a surface can be characterized by measuring the three-dimensional thermal mobility of the particle. As a model analyte we use four different lengths of dsDNA to bind the particle to the surface (590 bp/201 nm, 290 bp/99 nm, 141 bp/48 nm and 105 bp/36 nm). Plots of the minimum height, average height and maximum height as function of the in plane particle position reflect the differences in bond length, bond flexibility and bond orientation of the different DNA molecules. We also analyze ensembles of particles bound to the four DNA lengths and show that the height displacement is at maximum equal to the bond length, but large variations between particles are observed, which we attribute to non-specific interactions. The mobility of a bound particle can be influenced by external forces. We show that a magnetic force towards the surface brings bound particles on average closer to the surface. However, a magnetic force away from the surface does not always brings bound particles away from the surface, but can lead to medium or minimum heights. This can be explained by magnetic anisotropy in the particles, leading to particle alignment and subsequent height reduction. We describe a model that shows how particle alignment due to magnetic anisotropy brings bound particles into well-defined three-dimensional positions. Although particle alignment may interfere with the desired magnetic manipulation, it can also lead to additional information on for example rotational freedom of the bond and bond flexibility. Finally, we show that a bound particle can also be pulled away from the surface by an electrostatic force induced by replacing the buffer with a buffer of low ionic strength. We show that the height modulation is dependent on both the analyte length and the ionic strength, and describe a quantitative model to account for the measured height displacements for particles bound to four different lengths of DNA. The improved knowledge on the magnetic properties of individual particles and the mobility of individual particles bound to a biosensor surface, resulting from the experiments described in this thesis, may lead to improved detection limits and enhanced specificity in future biosensors