Mu Chiao

Professor

Relevant Degree Programs

 

Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - Mar 2019)
Robust and optimal switching linear parameter-varying control (2018)

No abstract available.

Magnetically actuated MEMS devices for active control of cell migration (2015)

The ability of living cells to sense and respond to mechanical cues from the surrounding environment has been the subject of much study. Over the past two decades, a variety of techniques have been used to apply mechanical stimuli and investigate cell response. Recently, with advances in the field of Microelectromechanical Systems, devices incorporating microscale actuators have been developed to apply forces and study the cell response of individual cells. Among these microdevices, micropillar arrays incorporating remotely actuated magnetic pillars have shown some success as combined actuation and sensing platforms for cell strain studies. However, issues associated with the complex fabrication techniques used, the low actuation forces generated and the high magnetic field gradients required for pillar actuation have hindered the wide-scale adoption of these devices by the general research community. Consequently, investigation into the use of these active micropatterned surfaces in eliciting or controlling specific cellular response on a multicellular level has yet to be undertaken. This thesis aims to investigate the application of remotely actuated micropillar surfaces in controlling the migration behavior of cells on a multicellular level. First, using a novel custom-made magnetically actuated cell strain assessment tool, conventional tests are performed on endothelial cells to determine the minimum strain requirements for eliciting cell response. Then, a new technique for fabrication and patterning of magnetic micropillar arrays is developed to overcome the complexities of previous fabrication methods. Using the newly developed fabrication technique, magnetic micropillar arrays of various dimensions are fabricated and their mechanical, magnetic and material properties are characterized. The fabricated magnetic micropillars generate forces of several hundred nanonewtons at moderate magnetic fields of 100mT and are favorable to previous state-of-the-art. Finally, a cell migration chip comprising various micropillar topologies is developed and the migration behavior and migration rates of sheets of cells on the micropillar surfaces in the presence and absence of micropillar actuation is studied using in-vitro experiments. We show that actuated micropillar surfaces significantly impede cell migration, reducing cell migration rates by up to 85%. The magnetically actuated micropillar surfaces could have possible in-vivo applications for preventing cell-migration induced biofouling of medical implants.

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Microfabricated electromagnetic actuators for confocal measurements and imaging (2013)

Various optical microscopy techniques have been developed for micrometer level imaging of biological tissue samples. Among those techniques, confocal imaging provides superior image contrast and high resolution with a modest system cost. Confocal microscopy allows vertical optical sectioning (imaging a section perpendicular to the surface of tissue) or horizontal optical sectioning (imaging a section parallel to the surface of tissue) and provides high-resolution tissue morphology that is analogous to conventional histopathology images. This has brought up a tremendous potential for guiding surgical biopsies and in vivo non-invasive diagnosis of diseases such as cancer. The challenge in moving microscopic imaging modalities into clinical applications is miniaturization into a form of hand-held devices or catheters for endoscopic applications.In this thesis, micro-fabrication techniques such as Microelectromechanical Systems (MEMS) fabrication process and laser micromachining have been employed to develop magnetic actuators. The actuators are then used to move lenses and optical fibers in order to scan a laser beam across a sample. Lens and fiber actuators are integrated in catheter and hand-held devices for confocal thickness measurement and optical sectioning imaging of biological samples.Thickness measurement is performed by scanning the focal point of a microlens across the thickness of thin films or layered biological tissues and collecting the intensity signal of the single scattering light reflected back from the samples as a function of lens position. A catheter was developed and thickness measurements of polymer layers and biological tissues were demonstrated. The device has optical resolution of 32 µm with expanded uncertainty of measurement of 11.86 µm. Lens and fiber optic actuators have been coupled to form two-dimensional imaging devices. Direct and real-time vertical and horizontal cross-sectional imaging of biological samples has been demonstrated. Vertical imaging is performed by transverse (X-axis) and axial (Z-axis) scanning of a focused laser beam using an optical fiber and a microlens actuator respectively. Horizontal imaging is done by a 2-axis fiber optic scanner. All the developed actuators are driven by electromagnetic forces and require low driving voltages. Confocal imaging of biological samples, with lateral resolution of 1.55 µm, has been demonstrated.

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A battery-less MEMS device for on-demand and controlled drug delivery (2011)

Drug therapy efficacy depends on therapeutic concentrations of drugs at disease sites. An ideal controlled and localized drug delivery system would deliver drugs to a target tissue and would locally maintain the required drug concentration. Furthermore, for many diseases, the delivery of therapeutic concentrations on an “on-demand” basis would be of tremendous benefit.In this thesis, a MEMS (Microelectromechanical Systems) based drug delivery device has been developed that provides on-demand release of defined drug quantities. The device consists of a drug-loaded microreservoir that is sealed with an elastic PDMS (polydimethylsiloxane) magnetic membrane with a laser-drilled aperture. The drug release is triggered in the presence of an external magnetic field by deforming the magnetic membrane and therefore discharging the drug solution. The use of magnetic actuation for on-demand and controlled dose sequencing eliminates the need for an on-board power source. A new magnetic membrane material has been developed for the proposed drug delivery device. The polymeric magnetic composites were developed by incorporating coated iron oxide nanoparticles within a PDMS matrix. The new composites show improvement in reducing particle agglomeration compared to existing polymeric magnetic materials. Free-standing PDMS magnetic membranes with a thickness of 35 µm have been fabricated and have shown to deflect in applied magnetic fields. The MEMS drug delivery device has been used to deliver an antiproliferative, taxane-based drug, docetaxel (DTX). On-demand and controlled release of DTX with a dosage suitable for treatment of diabetic retinopathy has been achieved for 35 days. Biological activity of the released DTX was investigated two months after the drug was packaged in the device. These studies confirmed that the antiproliferative effect of DTX can be maintained for 2 months, and the drug does not degrade within the device. This device is a proof-of-concept development for on-demand and controlled delivery of taxane-based agents for treatment of proliferative retinopathy, which requires accurate delivery of nanomolar drug concentrations.

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MEMS pressure, temperature and conductivity sensors for high temperature and harsh environments (2011)

Kraft pulp digesters have been used to convert wood chips into pulp for manufacturing a wide variety of paper products. Inside a kraft digester, chemical reactions remove lignin from their wood matrix in a caustic environment (pH~13.5, 170°C, 2MPa). Data on actual internal operating conditions in a kraft digester is needed to optimize kraft digester operation and obtain maximum production quality. Currently, this information is limited to selected static locations on the periphery of the digester. The objective of this thesis is to develop miniature temperature, pressure, and liquid conductivity sensors for use in autonomous flow-following SmartChips to measure kraft process variables within the digester during their passage through the process. Combined capacitive pressure and temperature sensors were fabricated by bonding silicon and Pyrex chips using a new polymeric gap-controlling layer and a high temperature adhesive. A simple chip bonding technique involving insertion of the adhesive into the gap between two chips was developed. A silicon dioxide layer and a thin layer of Parylene were deposited to passivate the pressure sensor diaphragm against the caustic environment in kraft digesters. The sensors were characterized at both high temperatures and pressures and no signs of corrosion could be identified on the sensors.Integrated piezoresistive pressure and temperature sensors consisting of a square silicon diaphragm and high resistance piezoresistors were developed. A new Parylene and silicone conformal coating process were developed to passivate the pressure sensors against the caustic environment. The sensors were characterized up to 2MPa and 180°C in an environmental chamber. The sensors’ resistances were measured before and after testing in a kraft pulping cycle and showed no change in their values. SEM pictures and topographical surface analyses were also performed before and after pulp liquor exposure and showed no observable changes.Combined liquid conductivity and temperature sensor packages consisting of a platinum resistance temperature detector (RTD) and a four-electrode conductivity sensor formed by stainless steel electrodes and installed on a polyetheretherketone (PEEK) enclosure were developed. The sensors were characterized up to 180°C at NaOH concentrations of 10-100g/l in the presence of wood chips and survived with no signs of corrosion.

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MEMS-based anti-biofouling - mechanism, devices and application (2009)

A novel anti-biofouling mechanism based on the combined effects of electric field and shear stress was reported. The mechanism was observed in millimeter-scale piezoelectric plates coated with different metal materials and microfabricated Micro-Electro-Mechanical Systems (MEMS) devices. Experimental observation on the quantities of protein desorption and theoretical calculations on surface interactions (van der Waals, electrostatic, hydrophobic, shear stress) have been carried out. This anti-fouling mechanism can also be activated by a vibrating micromachined Si/SiO₂ membrane. The combined effect of polyethylene glycol (PEG) grafting and application of vibration on attenuation of protein adsorption was also investigated. Vibrating PEG-grafted surfaces significantly attenuate protein adsorption, especially at low PEG grafting densities. Polymer steric interaction dominates over vibration interaction with protein on surfaces with high PEG grafting densities.Monothiol-functionalized hyperbranched polyglycidols (HPG-SH) were synthesized and self-assembled on the gold surface. The characteristics of the polymer were studied and compared with linear PEG using various surface analysis techniques. This hyperbranched polyglycidol is more resistant to protein adsorption than is linear PEG of similar molecular weight. In addition, higher molecular weight HPG shows less protein adsorption than does lower molecular weight HPG.The hyperbranched polyglycidols (without a thiol group) were further modified to generate functionality for microchannel-based liquid chromatography applications. The microchannel surface was first amino modified by allylamine plasma, and amino groups then reacted with N-hydroxy succinimide-functionalized HPGs to form strong amide bonds. The grafted HPGs are resistant to nonspecific protein adsorption. The succinimidyl ester groups degrade in water to form carboxyl groups on HPGs. By giving extra carboxyl groups to each HPG, the HPG can selectively capture positive avidin from a mixture of avidin and bovine serum albumin (BSA). To increase the capture efficiency, the microchannel was integrated with micropillar arrays as the liquid chromatography column.

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Master's Student Supervision (2010-2017)
Design, fabrication and characterization of a double-network alginate-pHEMA hydrogel coating for PDMS-based biomedical implants (2017)

Traditional silicone biomedical implants, such as urinary catheters, often suffer from high surface friction, high stiffness, and a lack of hydrophilicity, which can cause discomfort or discomfort. To tackle these challenges, we developed a double-network alginate-pHEMA hydrogel “cushion” coating for polydimethylsiloxane (PDMS) biomedical implants. The double-network hydrogel presented here consists of two distinct networks made of alginate and pHEMA, respectively. The alginate network is covalently bonded to PDMS substrates as scaffolding, and the denser pHEMA network fills the free space within the alginate network. In this proof of concept study, the double-network hydrogel achieved a compressive fracture stress of 502.04±14.41 kPa, which is 5.8-fold stronger than the alginate hydrogel, while its elasticity is still comparable to soft tissues. The proposed double-network hydrogel has a negligible amount of swelling in biological fluids and exhibits no cytotoxicity, which are desirable qualities for biomedical and coating applications. Both chemical modification using APTES and micropillar anchors have been used to improve the coating stability. We found that the adhesion strength of the hydrogel coating on micropillar PDMS substrates is 55% stronger than on bare PDMS substrates when both substrates are grafted with APTES. In comparison to native PDMS and K-Y Jelly-lubricated PDMS, the double-network alginate-pHEMA hydrogel-coated PDMS demonstrated significantly less friction and superior hydrophilicity.

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Design, fabrication, and characterization of a magnetic porous pdms as an on-demand drug delivery device (2016)

We introduce a novel, on-demand drug delivery device based on a biocompatible magnetic sponge. The sponge is made of a porous polydimethylsiloxane (PDMS) mixed with carbonyl iron (CI) particles. The sponge is deformed under a magnetic field and consequently leads to releasing its contents. As a proof of concept study, three different CI/PDMS wt% ratios of 50%, 100%, and 150% were selected where, the 100% showed the most deformation under various magnetic fields. Although this sponge can solely be used as a potential drug delivery agent, a separate reservoir has been fabricated to protect the sponge and control the release rate. The final device has a diameter of 6 mm with a thickness of 2 mm. Controlled release of methylene blue (MB) and docetaxel (DTX) have been investigated to demonstrate the consistency and flexibility in adjusting the release rate from the device to suit different treatment requirements. Ex vivo tissue implantation has also been accomplished. This device is able to be implanted and deliver therapeutic agents at prescribed dosages.

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A 3d printing and moulding method of the fabrication of a miniature voice coil motor actuator (2015)

The goal of this project is to apply 3D printing and moulding (3DPM) methods for the fabrication of a miniature magnetic actuator for optical image stabilization (OIS) applications. Polydimethylsiloxane (PDMS) and strontium ferrite (SrFe) nano powder were used as the main structural material. Young’s modulus and the magnetization of the material with SrFe-doping ratios ranging from 20% to 60% by weight were characterized. The actuator, consisting of four coils, an actuating plate, and a base supporter was assembled and tested with a Laser Doppler Velocimetry (LDV) system. A tilting angle of 0.6º was achieved with the application of 500 mA (50 turns/9 mm long coils). A Taguchi’s orthogonal experimental design was used in the finite element analysis (FEA) simulation to examine the effect of dimension variations on the eigenfrequencies. Frequency response of the actuator was characterized and the experimental results matched with the simulation results between 1 and 450 Hz showing less than 5% errors. A series of replica experiments were also performed and analyzed.

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A minimally-invasive MEMS drug delivery device for the treatment of prostate cancer (2015)

We have developed a cylindrical shape magnetically-actuated MEMS drug delivery device for localized prostate cancer treatment. The device is small enough for implantation through a needle with minimally invasive procedures with potentially fewer side effects compared with full prostate removal. This method of implantation will be similar to brachytherapy, a standard procedure to implant radioactive seeds inside the prostate through a needle. The drug delivery device consists of a drug reservoir, a PDMS membrane, a magnetic block and housing. Docetaxel (DTX), an anti-proliferative drug, is deposited in the reservoir in solid form. The reservoir is then filled with fluids to form a saturated drug solution. When an external magnetic field is applied, it attracts the magnetic block towards the positive field gradient and causes the membrane to deflect. As a result, DTX is discharged from the reservoir, through a laser-drilled aperture on the membrane and into the housing. The housing has a 10 mm long opening which allows the released drug to diffuse to the surrounding tissues while it would prevent the tissues from touching the thin membrane.We have achieved a 1.8 fold increase of the actuating distance and a 3.6 fold increase in the magnetic force compared to the state-of-the-art magnetically-actuated drug delivery devices under the same actuation parameters. We have also demonstrated device implantation with a needle into swine bladder tissue and successful drug release of the device in the tissue.

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A vertical and horizontal 3-axis hand-held confocal scanner for skin imaging applications (2015)

The goal of this project is to develop a hand-held size, confocal optical scanner for clinical skin imaging. Both vertical and horizontal image scanning have been successfully achieved. Vertical scanning is performed by a voice coil actuator in the Z axial direction and a resonant galvanometer scanner in the X lateral direction. Horizontal scanning is conducted with the same resonant galvanometer scanner and a regular galvo mirror in X and Y lateral directions. The vertical imaging plane is perpendicular to the sample surface, while the horizontal imaging plane is parallel to the sample surface. The developed device is capable of providing image resolutions of 0.9-1.1μm and 5-8μm in the lateral and axial directions, respectively. The operational scanning speed is adjustable from 8 to 20 frames per second. Imaging results in both vertical and horizontal directions are presented with biological samples, including onion and mouse skin. By using this hand-held scanner, physicians may be able to reduce the number of unnecessary and repetitive biopsies, which will lower the cost to the health care system.

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Cardiomyocyte differentiation with cyclic mechanical strain (2015)

The creation of cardiomyocytes from pluripotent stem cells has the potential to revolutionize the treatment of heart disease, the discovery and testing of drugs, and our understanding of human physiology. Thus far, differentiation protocols have mainly focused on recapitulating the biochemical signalling events of cardiac organogenesis, and the resulting cardiomyocytes exhibit a fetal-like phenotype. We postulated that cyclic mechanical strain can mimic the mechanical environment of the developing heart, and, when applied in conjunction to biochemical differentiation protocols, can increase the efficiency of differentiation and the maturity of the resulting cells. Using an induced pluripotent stem cell line derived from human fibroblasts, we derived spontaneously contracting cardiomyocytes via treatment with activin A and bone morphogenetic protein 4 (BMP4). We observed that differentiation of induced pluripotent stem cells to cardiomyocytes is sensitive to cyclic strain, with the application of 5% continuous cyclic strain at 1Hz having the effect of inhibiting spontaneous contractions and disrupting sarcomere formation.

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A microsphere based microfluidic check valve (2011)

Biomedical applications of Micro-Electro-Mechanical System (MEMS) technology have sprung growth in the field of microfluidic systems and have been attracting much attention from scientific researchers and industry. Implantable drug delivery devices can deliver localized dosage which can reduce the side effects of medication. Such devices can maintain therapeutic concentrations of the drug over extended periods by providing small doses minimizing the risk of systemic toxicity.Recently, ocular drug delivery devices with micropumps using check valves have been demonstrated. The use of external magnetic actuation in a MEMS-based drug delivery device has been verified in reciprocating diaphragm micropumps. However, the magnetic diaphragm generates low pressures resulting in low flow rates (Re
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Surface elasticity models for static and dynamic response of nanoscale beams (2010)

Nanoscale beam-like structures have attracted much attention due to their superior mechanical properties for applications in nanomechanical and nanoelectromechanical systems (NEMS). Nanoscale structures are characterized by a high surface to volume ratio. The elastic response of surface layers of atoms is different from that of the bulk atoms due to reduced connectivity. Thus, surface energy has a significant effect on the response of nanoscale structures, and is associated with their size-dependent behavior. The classical continuum mechanics fails to capture the surface energy effects and hence is not directly applicable at nanoscale. To overcome this limitation, modified continuum models incorporating surface energy effects need to be developed in order to evaluate the size-dependent mechanical response of nanoscale structures.This thesis presents a modified continuum model and finite element formulation to study the static and dynamic response of nanoscale beams. The objective is to provide NEMS designers with an efficient set of tools that can predict static deflections, natural frequencies of vibrations, and uniaxial buckling loads of nanoscale beams with different geometries, applied forces, and boundary conditions. A general beam model based on Gurtin-Murdoch continuum surface elasticity theory is developed for the analysis of thin and thick beams of arbitrary cross-section. Closed-form analytical solutions for static bending of thin and thick beams under different loadings and boundary conditions are obtained. Their free vibration characteristics are also investigated. Analytical expressions for critical buckling loads of thin beam are presented. An intrinsic length scale depending on both surface and bulk elastic properties is defined to characterize surface energy effects in beam bending problems. The finite element simulation results of static bending, free vibration and axial buckling of nanoscale beams are compared with the analytical solutions for validation. Selected numerical results are presented for aluminum and silicon beams to demonstrate their salient response features. A technique is proposed to estimate surface elastic properties from measured natural frequencies of GaAs cantilever specimen. The surface elasticity continuum mechanics and finite element models developed in this work provide designers efficient tools to predict mechanical response of beam structures in nano devices.

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Recent Tri-Agency Grants

The following is a selection of grants for which the faculty member was principal investigator or co-investigator. Currently, the list only covers Canadian Tri-Agency grants from years 2013/14-2016/17 and excludes grants from any other agencies.

  • Thermal conductivity measurement of a new energy saving wall assembly - Natural Sciences and Engineering Research Council of Canada (NSERC) - Engage Grants Program (2016/2017)
  • Research in sensory information technologies and implementation in sleep disorder monitoring - Natural Sciences and Engineering Research Council of Canada (NSERC) - Strategic Partnership Grants for Projects (2016/2017)
  • 3D Thin-Film Coating for Micro/Nanodevice Study and Prototyping - Natural Sciences and Engineering Research Council of Canada (NSERC) - Research Tools and Instruments - Category 1 (2015/2016)
  • A new low-cost sensors for wearable devices - Natural Sciences and Engineering Research Council of Canada (NSERC) - Engage Grants Program (2015/2016)
  • Magnetic micropillar structures as mechanotransduction devices for cells - Natural Sciences and Engineering Research Council of Canada (NSERC) - Discovery Grants Program - Individual (2015/2016)
  • Dynamic Mechanical Analysis of Microstructures - Natural Sciences and Engineering Research Council of Canada (NSERC) - Research Tools and Instruments - Category 1 (2014/2015)
  • A new low cost device for skin monitoring - Mathematics of Information Technology and Complex Systems (MITACS) - Networks of Centres of Excellence (NCE) - Internship Funds (2014/2015)
  • Anti-biofouling mechanisms and devices for health applications - Natural Sciences and Engineering Research Council of Canada (NSERC) - Discovery Grants Program - Individual (2014/2015)
  • A new low-cost imaging device for skin cancer screening - Natural Sciences and Engineering Research Council of Canada (NSERC) - Engage Grants Program (2013/2014)
  • Development of a microlens module with image stabilization for mobile applications - Natural Sciences and Engineering Research Council of Canada (NSERC) - Strategic Projects (2013/2014)
  • A MEMS-based ocular drug delivery service - Natural Sciences and Engineering Research Council of Canada (NSERC) - Collaborative Health Research Projects (2013/2014)
  • Antibiofouling mechanisms, microdevices and applications to proteomics - Natural Sciences and Engineering Research Council of Canada (NSERC) - Discovery Grants Program - Individual (2013/2014)
  • Canada Research Chair Tier II - Dr. Mu Chiao - Canada Research Chairs - Canada Research Chair Tier II (NSERC) (2013/2014)
 
 

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