Biosensors to Monitor Cell Activity in 3D Hydrogel-Based Tissue Models

Three-dimensional (3D) culture models have gained relevant interest in tissue engineering and drug discovery owing to their suitability to reproduce in vitro some key aspects of human tissues and to provide predictive information for in vivo tests. In this context, the use of hydrogels as artificial extracellular matrices is of paramount relevance, since they allow closer recapitulation of (patho)physiological features of human tissues. However, most of the analyses aimed at characterizing these models are based on time-consuming and endpoint assays, which can provide only static and limited data on cellular behavior. On the other hand, biosensing systems could be adopted to measure on-line cellular activity, as currently performed in bi-dimensional, i.e., monolayer, cell culture systems; however, their translation and integration within 3D hydrogel-based systems is not straight forward, due to the geometry and materials properties of these advanced cell culturing approaches. Therefore, researchers have adopted different strategies, through the development of biochemical, electrochemical and optical sensors, but challenges still remain in employing these devices. In this review, after examining recent advances in adapting existing biosensors from traditional cell monolayers to polymeric 3D cells cultures, we will focus on novel designs and outcomes of a range of biosensors specifically developed to provide real-time analysis of hydrogel-based cultures

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

Microfluidics for Biosensing and Diagnostics

Efforts to miniaturize sensing and diagnostic devices and to integrate multiple functions into one device have caused massive growth in the field of microfluidics and this integration is now recognized as an important feature of most new diagnostic approaches. These approaches have and continue to change the field of biosensing and diagnostics. In this Special Issue, we present a small collection of works describing microfluidics with applications in biosensing and diagnostics

The 2019 surface acoustic waves roadmap

Today, surface acoustic waves (SAWs) and bulk acoustic waves are already two of the very few phononic technologies of industrial relevance and can been found in a myriad of devices employing these nanoscale earthquakes on a chip. Acoustic radio frequency filters, for instance, are integral parts of wireless devices. SAWs in particular find applications in life sciences and microfluidics for sensing and mixing of tiny amounts of liquids. In addition to this continuously growing number of applications, SAWs are ideally suited to probe and control elementary excitations in condensed matter at the limit of single quantum excitations. Even collective excitations, classical or quantum are nowadays coherently interfaced by SAWs. This wide, highly diverse, interdisciplinary and continuously expanding spectrum literally unites advanced sensing and manipulation applications. Remarkably, SAW technology is inherently multiscale and spans from single atomic or nanoscopic units up even to the millimeter scale. The aim of this Roadmap is to present a snapshot of the present state of surface acoustic wave science and technology in 2019 and provide an opinion on the challenges and opportunities that the future holds from a group of renown experts, covering the interdisciplinary key areas, ranging from fundamental quantum effects to practical applications of acoustic devices in life science

Study of particle suspensions in microfluidics for the development of optical devices

The vision of this PhD research project is to create a microfluidic system for controlling the locations of suspended particles in order to form three dimensional (3D) objects on demand. To realize this, the author implemented a microfluidic system that can apply suitable and desired forces on particles on demand. Particles of various refractive indices were placed close to each other in order to form a media having reconfigurable and tuneable properties. Light was coupled into such well-controlled particles in order to form dynamically tuned objects suspended in liquid such as optical waveguides. The dielectrophoretic (DEP) force was used for manipulating the locations of particles as it is capable of focusing and scattering suspended particles from pre-determined locations. Additionally, when combined with hydrodynamic forces, the DEP force was able to form densely packed areas of such particles with non-turbulent boundaries. The research was implemented in three stages. In the first stage, the author utilized a platform consisting of a microfluidic system integrated with DEP microelectrodes, microfluidics and optical peripherals for the coupling of light. Light was directly coupled into densely packed silicon dioxide (SiO2) particles with diameters of 230 and 450 nm, respectively. Light was transmitted via the closely packed 230 nm particles and in contrast was significantly scattered by the 450 nm particles. The outcomes, which were resulted from this initial stage, were the first demonstration of a dynamically tuneable optical waveguide based on the DEP focused particles in microfluidics. In the second stage of his research, the author integrated a multi mode polymeric waveguide into the microfluidic system. Tungsten trioxide (WO3) and SiO2 particles with diameters of 80 and 450 nm were investigated. The findings demonstrated that the densely packed WO3 particles were able to couple light from the polymeric waveguide, while the SiO2 particles did not affect the transmission of the optical signals significantly. The investigations of the second stage platform resulted in the first demonstration of optical waveguide tuning based on DEP focused particles. Finally, in the third stage of this research, the author implemented a quasi single mode polymeric waveguide integrated with the microfluidics. The author used WO3, zinc oxide (ZnO) and SiO2 particles with diameters of 80, 50 and 72 nm, respectively. Under the DEP force, these particles were able to interact with the optical guided modes. The results show that the WO3 particles were capable of forming layers of packed particles with anti-resonant characteristics. In particular, the fundamental mode was strongly coupled to the packed WO3 particles. However, under certain particle focusing conditions, the first order mode was anti-resonant to the closely packed WO3 particles as it was largely isolated. These findings were the first demonstration of the coupling and manipulation of optical guided modes using DEP focused particles with resonant and anti-resonant behaviors

A transistor based sensing platform and a microfluidic chip for a scaled-up simulation of controlled drug release

The framework of my thesis are Biomedical (or Biological) Microelectromechanical Systems (BioMEMSs). Two fields in which this discipline is involved are sensors and fluidics. Functionalized organic materials are under investigation to be the means for target biological sensing, and sensors are evolving to be integrated in fluidics platforms in order to produce in the future new small portable diagnostic devices. On the other hand one of the challenges of micro and nanofluidic technology is the fabrication of drug release devices, in order to control the amount of drug present in an organism. In this thesis these two arguments are considered. First we will discuss the implementation of a process oriented to the fabrication of an hybrid Organic Field Effect Transistor (OFET) with sensing capabilities from the semiconductive layer. In the second part we will show the fabrication process of a silicon based structure for the scaled-up characterization of drugs in nanochannels for controlled drug release. The characterization will consider charged microspheres playing the role of drugs to be tracked with a microscope. We will highlight also the possibility of implementing the transistor related technology in nanofluidic systems for the electronic controlled drug release