Sonocytology: dynamic acoustic manipulation of particles and cells

Separating and sorting cells and micro-organisms from a heterogeneous mixture is a fundamental step in biological, chemical and clinical studies, enabling regenerative medicine, stem cell research, clinical sample preparation and improved food safety. Particle and cell manipulation by ultrasound acoustic waves provides the capability of separation of cells on the basis of their size and physical properties. Offering the advantages of relatively large microfluidic volumes in a label-free, contactless and biocompatible manner. Consequently, the discovery of alternative methods for precise manipulation of cells and particles is of highly demand. This thesis describes a novel approach of ultrasound acoustic manipulation of particles and cells. The principle of operation of the dynamic acoustic field method is described accompanied with acoustic separation simulations. Furthermore, the complete fabrication and characterisation of two types of ultrasound devices is given. The first one is a bulk acoustic wave (BAW) device and the second is a surface acoustic wave (SAW) device. Successful experiments using the BAW device for sorting different diameter particles with a range from 5 to 45 μm are demonstrated, also experiments for sorting particles depending on their density are presented. Moreover, experiments of the proposed method for sorting porcine dorcal root ganglion (DRG) cells from a heterogeneous mixture of myelin debris depending on their size are displayed. Experimental results of sorting cells depending on their stiffness are demonstrated. Experiments using the fabricated SAW device for sorting different diameter particles in a constant flow with a range from 1 μm to 10 μm are presented. Furthermore, experiments of the proposed method for sorting live from dead Htert cells depending on their mechanical properties, i.e. stiffness are displayed. As a side project a new idea for dynamic acoustic manipulation by rotating the acoustic field is demonstrated. The basic principles of this method and the simulations for verifying this concept are displayed. Experiments for sorting 10 μm from 3 μm polystyrene particles are presented, with two different types of the dynamic acoustic rotating field being examined

Hybridising Photonic and Biotechnologies to CMOS

Complementary metal oxide semiconductor (CMOS) technology lies at the heart of all computing and communications equipment, and has also been very successful as an image sensing technology, revolutionising digital imaging. New possibilities for CMOS are now being explored and delivered, including applications in gene sequencing, cell sorting, terahertz imaging and image fusion. We present recent data on the development of ion sensitive field effect transistors for large scale arrays used in gene sequencing and chemical imaging. These devices are capable of following proton ion evolution and diffusion sufficiently fast to be able to measure the ion dynamics in an aqueous medium. These dynamic capabilities are further exploited to demonstrate the measurement of enzyme kinetics on a CMOS chip. We also present advances in photonic technologies on CMOS and how they can be exploited for terahertz imaging and potential multispectral imaging on a chip. Finally, we present results on the development of single photon counting technology and its integration with acoustic particle sorting, presenting a future avenue for hand-held cell sorting and manipulation systems