Contactless acoustic micro/nano manipulation:a paradigm for next generation applications in life sciences

Acoustic actuation techniques offer a promising tool for contactless manipulation of both synthetic and biological micro/nano agents that encompass different length scales. The traditional usage of sound waves has steadily progressed from mid-air manipulation of salt grains to sophisticated techniques that employ nanoparticle flow in microfluidic networks. State-of-the-art in microfabrication and instrumentation have further expanded the outreach of these actuation techniques to autonomous propulsion of micro-agents. In this review article, we provide a universal perspective of the known acoustic micromanipulation technologies in terms of their applications and governing physics. Hereby, we survey these technologies and classify them with regards to passive and active manipulation of agents. These manipulation methods account for both intelligent devices adept at dexterous non-contact handling of micro-agents, and acoustically induced mechanisms for self-propulsion of micro-robots. Moreover, owing to the clinical compliance of ultrasound, we provide future considerations of acoustic manipulation techniques to be fruitfully employed in biological applications that range from label-free drug testing to minimally invasive clinical interventions

Embedded Microbubbles for Acoustic Manipulation of Single Cells and Microfluidic Applications.

Acoustically excited microstructures have demonstrated significant potential for small-scale biomedical applications by overcoming major microfluidic limitations. Recently, the application of oscillating microbubbles has demonstrated their superiority over acoustically excited solid structures due to their enhanced acoustic streaming at low input power. However, their limited temporal stability hinders their direct applicability for industrial or clinical purposes. Here, we introduce the embedded microbubble, a novel acoustofluidic design based on the combination of solid structures (poly(dimethylsiloxane)) and microbubbles (air-filled cavity) to combine the benefits of both approaches while minimizing their drawbacks. We investigate the influence of various design parameters and geometrical features through numerical simulations and experimentally evaluate their manipulation capabilities. Finally, we demonstrate the capabilities of our design for microfluidic applications by investigating its mixing performance as well as through the controlled rotational manipulation of individual HeLa cells

Advanced medical micro-robotics for early diagnosis and therapeutic interventions

Recent technological advances in micro-robotics have demonstrated their immense potential for biomedical applications. Emerging micro-robots have versatile sensing systems, flexible locomotion and dexterous manipulation capabilities that can significantly contribute to the healthcare system. Despite the appreciated and tangible benefits of medical micro-robotics, many challenges still remain. Here, we review the major challenges, current trends and significant achievements for developing versatile and intelligent micro-robotics with a focus on applications in early diagnosis and therapeutic interventions. We also consider some recent emerging micro-robotic technologies that employ synthetic biology to support a new generation of living micro-robots. We expect to inspire future development of micro-robots toward clinical translation by identifying the roadblocks that need to be overcome

Gas Flows in Microsystems

International audienc

Innovative designs and applications of Janus micromotors with (photo)-catalytic and magnetic motion

El objetivo principal de esta Tesis Doctoral es el diseño y desarrollo de micromotores Janus biocompatibles y su aplicación en ámbitos relevantes de la salud y de la protección medioambiental. Los micromotores Janus son dispositivos en la microescala autopropulsados que tienen al menos dos regiones en su superficie con diferentes propiedades físicas y químicas, lo que les convierte en una clase distintiva de materiales que pueden combinar características ópticas, magnéticas y eléctricas en una sola entidad. Como la naturaleza del micromotor Janus -el dios romano de las dos caras- los objetivos de esta Tesis Doctoral presentan naturaleza dual y comprenden desarrollos de química fundamental y de química aplicada. En efecto, por una parte, el objetivo central aborda el diseño, síntesis y ensamblaje, así como la caracterización de micromotores Janus poliméricos propulsados por mecanismos (foto)-catalíticos y/o accionados por campos magnéticos. Por otra parte, el objetivo central implica la aplicación de los micromotores desarrollados para resolver desafíos sociales relevantes en los ámbitos químico-analítico, biomédico y ambiental. Partiendo de estas premisas, en la primera parte de la Tesis Doctoral, se sintetizaron micromotores Janus de policaprolactona propulsados químicamente integrando nanomateriales para el diseño de sensores móviles para la detección selectiva de endotoxinas bacterianas. De esta forma, el movimiento autónomo del micromotor mejora la mezcla de fluidos y la eficacia de las reacciones implicadas permitiendo detectar el analito en pocos minutos, incluso en muestras viscosas y medios donde la agitación no es posible. Además, esta autopropulsión es altamente compatible con su empleo en formatos ultra-miniaturizados para el desarrollo de futuros dispositivos portátiles en el marco de la tecnología point of care para aplicaciones clínicas y agroalimentarias. Con el fin de incrementar su biocompatibilidad para aplicaciones in vivo, en una segunda etapa de la Tesis Doctoral, se diseñaron micromotores Janus con propulsión autónoma utilizando luz visible para la eliminación de toxinas relevantes en procesos inflamatorios. El fenómeno autopropulsivo del micromotor y su capacidad de interacción con agentes tóxicos condujo a metodologías más rápidas y eficaces infiriéndose un futuro prometedor de estos micromotores para el tratamiento del shock séptico o intoxicación. En una tercera etapa, se sintetizaron micromotores propulsados por campos magnéticos. Estos micromotores utilizan una aproximación elegante de propulsión, exenta del empleo de combustibles químicos tóxicos como sucede en la propulsión catalítica y, en consecuencia, biocompatible. Asimismo, este mecanismo propulsivo permite controlar e incluso programar su trayectoria para aplicaciones que requieran de un guiado y de un control preciso de esta. De manera específica, estos micromotores han sido aplicados en esta Tesis Doctoral para la liberación controlada de fármacos en el tratamiento de cáncer pancreático y como elementos de remediación ambiental en la eliminación de agentes nerviosos en aguas contaminadas

Advanced medical micro-robotics for early diagnosis and therapeutic interventions

Recent technological advances in micro-robotics have demonstrated their immense potential for biomedical applications. Emerging micro-robots have versatile sensing systems, flexible locomotion and dexterous manipulation capabilities that can significantly contribute to the healthcare system. Despite the appreciated and tangible benefits of medical micro-robotics, many challenges still remain. Here, we review the major challenges, current trends and significant achievements for developing versatile and intelligent micro-robotics with a focus on applications in early diagnosis and therapeutic interventions. We also consider some recent emerging micro-robotic technologies that employ synthetic biology to support a new generation of living micro-robots. We expect to inspire future development of micro-robots toward clinical translation by identifying the roadblocks that need to be overcome

Elasto-Magnetic Pumps for Point-of-Care Diagnostics

In recent decades the development of microfluidic lab-on-a-chip devices has accelerated dramatically, revolutionising the fields of microbiology and medicine. However, these systems are not without limitations. Many of these devices are powered by comparatively large and expensive external pumping systems, which limit their widespread applications in areas such as point of care medical devices. As such there is a need to carry out research into miniaturising the pumping systems in order to be integrated directly within the device. The same is true for the reliance on macroscopic sample preparation such as particle filtration. This thesis will focus on a new class of elasto-magnetic pumps and the physical rinciples underpinning their functionality when integrated within microfluidic lab-on-a-chip devices, as well as investigating the novel use of herringbone micromixers for particle filtration.Operating Budge

Acoustofluidic manipulation of cells

This thesis aims to investigate the manipulation of cells, especially cancer cells, via acoustofluidic techniques at high ultrasound frequencies. This PhD project's motivation and ultimate goal are to separate circulating tumour cells (CTCs) from normal blood cells to achieve CTCs detection via acoustofluidic techniques. At the same time, the acoustofluidics-based manipulation of other types of cells and microparticles have also been investigated. The presence of rare cancer cells in cancer patient blood, called CTCs, has been increasingly researched as an essential biomarker for cancer diagnosis and cancer treatment monitoring. Separation and enrichment of CTCs from cancer patients’ blood samples via liquid biopsy methods have shown excellent compatibility compared with the conventional screening and invasive tissue biopsy methods. As a novel, bio�compatible and label-free technique, acoustofluidics has the potential to become an effective tool to sort CTCs from liquid samples or manipulate other types of cells via the cells physical properties: size, density, and compressibility. In this thesis, acoustofluidic platforms based on standing surface acoustic waves (SSAW) are demonstrated, including the Interdigital transducers (IDTs) design, cleanroom (CR) fabrication, and integration with microfluidics, electronics and mechanics systems. The simulation has been conducted via Governing equations (Continuity and Navier-Stokes equation) and Finite Element Method (FEM) model to understand the working principle and compare it with the microparticles manipulation experiment on the parallel and tilted-angle IDT SSAW devices. Moreover, a conventional tilted-angle (CTA) IDTs acoustofluidic device has been applied to wash the electroporated cells from the original medium, and a higher electroporation efficiency and cell viability are achieved. By optimising the IDTs patterning, a filled tilted-angle (FTA) IDTs design with less electrical input power but higher acoustic energy generated compared with CTA IDTs is demonstrated that achieves around 90% deflection efficiency of Hela cells with the input power of 4.5 W. In addition, to overcome the challenges of frangibility and overheating due to the conventional SSAW substrates, a novel Gallium Nitride (GaN) compound semiconductor film based acoustic tweezer is demonstrated. Cancer cell patterning via the GaN platform has been successfully achieved with excellent thermal stability with high input power. SSAW-based acoustofluidic cell manipulation in this thesis extends understanding of acoustofluidics techniques via the novel IDT design and SSAW generation substrate and will enable further development in high precision cell manipulation and biosensors application

Biophysical investigations of single cells with optically actuated microtools

I demonstrated that optical tweezer-based techniques are capable to explore living cells physical and biochemical properties. For example the measurement of Young’s modulus of endothelial cells or determination of adhesion force of preliminary functionalized microtools. These experiments could be carried out with precisely manipulated two-photon polymerized, purpose designed microstructures. In my thesis I investigated the glutathione's adhesion forces to brain endothelial cells using our novel holographic optical tweezer-based binding force measurement technique. In this series of experiments the used micromanipulators could prevent the cells from photodamage, furthermore the laser microfabrication made it possible to easily change the geometry of the micromanipulator’s probe as the experimental methodology required. In both type of measurement arrangements, we used a cell culturing method where the cells were grown on mask-lithography made walls, which were parallel to the optical axis what enabled us to measure the adhesion force and the stiffness in a direction perpendicular to the cell membrane by approximation of the cell via lateral movement of the trapped microstructure. Our method could be extended in the future to differentiate between multiple and single binding events, to characterize other BBB targeting ligands with the adhesion force on living cells or even to select novel targeting molecules. The functionalization protocol could be easily adapted to immobilize those molecules with covalent bonds, thanks to the variety of PEG-linkers