33 research outputs found
Development of Microwave/Droplet-Microfluidics Integrated Heating and Sensing Platforms for Biomedical and Pharmaceutical Lab-on-a-Chip Applications
Interest in Lab-on-a-chip and droplet-based microfluidics has grown recently because of their promise to facilitate a broad range of scientific research and biological/chemical processes such as cell analysis, DNA hybridization, drug screening and diagnostics. Major advantages of droplet-based microfluidics versus traditional bioassays include its capability to provide highly monodispersed, well-isolated environment for reactions with magnitude higher throughput (i.e. kHz) than traditional high throughput systems, as well as its low reagent consumption and elimination of cross contamination. Major functions required for deploying droplet microfluidics include droplet generation, merging, sorting, splitting, trapping, sensing, heating and storing, among which sensing and heating of individual droplets remain great challenges and demand for new technology. This thesis focuses on developing novel microwave technology that can be integrated with droplet-based microfluidic platforms to address these challenges.
This thesis is structured to consider both fundamentals and applications of microwave sensing and heating of individual droplets very broadly. It starts with developing a label-free, sensitive, inexpensive and portable microwave system that can be integrated with microfluidic platforms for detection and content sensing of individual droplets for high-throughput applications. This is, indeed, important since most droplet-based microfluidic studies rely on optical imaging, which usually requires expensive and bulky systems, the use of fluorescent dyes and exhaustive post-imaging analysis. Although electrical detection systems can be made inexpensive, label-free and portable, most of them usually work at low frequencies, which limits their applications to fast moving droplets. The developed microwave circuitry is inexpensive due to the use of off-the-shelf components, and is compact and capable of detecting droplet presence at kHz rates and droplet content sensing of biological materials such as penicillin antibiotic, fetal bovine serum solutions and variations in a drug compound concentration (e.g., for Alzheimer’s Disease).
Subsequently, a numerical model is developed based on which parametrical analysis is performed in order to understand better the sensing and heating performance of the integrated platform. Specifically, the microwave resonator structure, which operates at GHz frequency affecting sensing performance significantly, and the dielectric properties of the microfluidic chip components that highly influence the internal electromagnetic field and energy dissipation, are studied systematically for their effects on sensing and heating efficiency. The results provide important findings and understanding on the integrated device operation and optimization strategies.
Next, driven by the need for on-demand, rapid mixing inside droplets in many applications such as biochemical assays and material synthesis, a microwave-based microfluidic mixer is developed. Rapid mixing in droplets can be achieved within each half of the droplet, but not the entire droplet. Cross-center mixing is still dominated by diffusion. In this project, the microwave mixer, which works essentially as a resonator, accumulates an intensive, nonuniform electromagnetic field into a spiral capacitive gap (around 200 ÎĽm) over which a microchannel is aligned. As droplets pass by the gap region, they receive spatially non-uniform energy and thus have non-uniform temperature distribution, which induces non-uniform Marangoni stresses on the interface and thus three-dimensional (3D) chaotic motion inside the droplet. The 3D chaotic motion inside the droplet enables fast mixing within the entire droplet. The mixing efficiency is evaluated by varying the applied power, droplet length and fluid viscosity.
In spite of various existing thermometry methods for microfluidic applications, it remains challenging to measure the temperature of individual fast moving droplets because they do not allow sufficient exposure time demanded by both fluorescence based techniques and resistance temperature detectors. A microwave thermometry method is thus developed here, which relies on correlating fluid temperature with the resonance frequency and the reflection coefficient of the microwave sensor, based on the fact that liquid permittivity is a function of temperature. It is demonstrated that the sensor can detect the temperature of individual droplets with ±1.2 °C accuracy.
At the final part of the thesis, I extend my platform technology further to applications such as disease diagnosis and drug delivery. First, I develop a microfluidic chip for controlled synthesis of poly (acrylamide-co-sodium acrylate) copolymer hydrogel microparticles whose structure varies with temperature, chemical composition and pH values. This project investigates the effects of monomer compositions and cross-linker concentrations on the swelling ratio. The results are validated through the Fourier transform infrared spectra (FTIR), SEM and swelling test. Second, a preliminary study on DNA hybridization detection through microwave sensors for disease diagnosis is conducted. Gold sensors and biological protocols of DNA hybridization event are explored. The event of DNA hybridization with the immobilized thiol-modified ss-DNA oligos and complimentary DNA (c-DNA) are monitored. The results are promising, and suggests that microwave integrated Lab-on-a-chip platforms can perform disease diagnosis studies
Natural Convection in a Quadrantal Cavity Heated and Cooled on Adjacent Walls
In this study, experimental and numerical analyses of natural convection in a quadranta
Microwave temperature measurement in microfluidic devices
In spite of various existing thermometry methods for microfluidic applications, it remains challenging to measure the temperature of individual droplets in segmented flow since fast moving droplets do not allow sufficient exposure time demanded by both fluorescence based techniques and resistance temperature detectors. In this contribution, we present a microwave thermometry method that is non-intrusive and requires minimal external equipment. This technique relies on the correlation of fluid temperature with the resonance frequency of a microwave sensor that operates at a GHz frequency range. It is a remote yet direct sensing technique, eliminating the need for mixing fluorescent dyes with the working fluid. We demonstrated that the sensor operates reliably over multiple tests and is capable of both heating and sensing. It measures temperature to within +/- 1.2 degrees C accuracy and can detect the temperature of individual droplets
A Microfluidics-Assisted Double-Barreled Nanobioconjugate Synthesis Introducing Aprotinin as a New Moonlight Nanocarrier Protein: Tested toward Physiologically Relevant 3D-Spheroid Models
Proteins are promising substances for introducing new
drug carriers
with efficient blood circulation due to low possibilities of clearance
by macrophages. However, such natural biopolymers have highly sophisticated
molecular structures, preventing them from being assembled into nanoplatforms
with manipulable payload release profiles. Here, we report a novel
anticancer nanodrug carrier moonlighting protein, Aprotinin, to be
used as a newly identified carrier for cytotoxic drugs. The Aprotinin–Doxorubicin
(Apr–Dox) nanobioconjugate was prepared via a single-step microfluidics
coflow mixing technique, a feasible and simple way to synthesize a
carrier-based drug design with a double-barreled approach that can
release and actuate two therapeutic agents simultaneously, i.e., Apr–Dox
in 1:11 ratio (the antimetastatic carrier drug aprotinin and the chemotherapeutic
drug DOX). With a significant stimuli-sensitive (i.e., pH) drug release
ability, this nanobioconjugate achieves superior bioperformances,
including high cellular uptake, efficient tumor penetration, and accumulation
into the acidic tumor microenvironment, besides inhibiting further
tumor growth by halting the urokinase plasminogen activator (uPA)
involved in metastasis and tumor progression. Distinctly, in healthy
human umbilical vein endothelial (HUVEC) cells, drastically lower
cellular uptake of nanobioconjugates has been observed and validated
compared to the anticancer agent Dox. Our findings demonstrate an
enhanced cellular internalization of nanobioconjugates toward breast
cancer, prostate cancer, and lung cancer both in vitro and in physiologically
relevant biological 3D-spheroid models. Consequently, the designed
nanobioconjugate shows a high potential for targeted drug delivery
via a natural and biocompatible moonlighting protein, thus opening
a new avenue for proving aprotinin in cancer therapy as both an antimetastatic
and a drug-carrying agent
Effective Thermo-Capillary Mixing in Droplet Microfluidics Integrated with a Microwave Heater
In
this study, we present a microwave-based microfluidic mixer
that allows rapid mixing within individual droplets efficiently. The
designed microwave mixer is a coplanar design with a small footprint,
which is fabricated on a glass substrate and integrated with a microfluidic
chip. The mixer works essentially as a resonator that accumulates
an intensive electromagnetic field into a spiral capacitive gap (around
200 ÎĽm), which provides sufficient energy to heat-up droplets
that pass through the capacitive gap. This microwave actuation induces
nonuniform Marangoni stresses on the interface, which results in three-dimensional
motion inside the droplet and thus fast mixing. In order to evaluate
the performance of the microwave mixer, droplets with highly viscous
fluid, 75% (w/w) glycerol solution, were generated, half of which
were seeded with fluorescent dye for imaging purposes. The relative
importance of different driving forces for mixing was evaluated qualitatively
using magnitude analysis, and the effect of the applied power on mixing
performance was also investigated. Mixing efficiency was quantified
using the mixing index, which shows as high as 97% mixing efficiency
was achieved within the range of milliseconds. This work demonstrates
a very unique approach of utilizing microwave technology to facilitate
mixing in droplet microfluidics systems, which can potentially open
up areas for biochemical synthesis applications
Controlled Synthesis of Poly(acrylamide-<i>co</i>-sodium acrylate) Copolymer Hydrogel Microparticles in a Droplet Microfluidic Device for Enhanced Properties
In
this study, monodisperse polyÂ(acrylamide-<i>co</i>-sodium
acrylate) hydrogel microparticles with a controlled water
absorbance capacity were synthesized in a droplet microfluidic device
that can be used for enhanced oil recovery applications. The experimental
method and the microfluidic device were optimized to produce well-spaced
monodisperse monomer droplets that were then polymerized by UV initiation
in an oil reservoir. The monomer composition (acrylamide-to-sodium
acrylate weight ratio) and the cross-linker concentration were tailored
to increase the water absorbance capacity. The copolymer composition
was evaluated and confirmed by FTIR spectroscopy measurements. The
water absorbance capacity determined by swelling experiments agreed
very well with that predicted by Flory–Huggins swelling theory,
which relates swelling to the ionic content and the cross-linker concentration
Evaluation of the cytotoxic and genotoxic potential of lecithin/chitosan nanoparticles
WOS: 000329623000001Nanoparticles-based drug targeting delivery systems have been introduced in the treatment for various diseases because of their effective properties, although there have been conflicting results on the toxicity of nanoparticles. In the present study, the aim was to evaluate the cytotoxicity and the genotoxicity of different concentrations of lecithin/chitosan nanoparticles with and without clobetasol-17-propionate (CP) by neutral red uptake (NRU) cytotoxicity assay and single cell gel electrophoresis (Comet) and cytokinesis-blocked micronucleus assays. The IC50 values of lecithin/chitosan nanoparticles with/without CP were found as 1.9 and 1.8 %, respectively, in the NRU cytotoxicity test. High concentrations of lecithin/chitosan nanoparticles induced DNA damage in human lymphocytes as evaluated by comet assay. The micronucleus frequency was increased by the lecithin/chitosan treatment in a dose-dependent manner. Also at the two highest concentrations, a significant increase in micronucleus formation was observed. Lecithin/chitosan nanoparticles with CP did not increase the frequency of micronucleus and also did not induce additional DNA damage when compared with lecithin/chitosan nanoparticles without CP; therefore, CP itself has not found to be genotoxic at the studied concentration
Assessment of antibacterial activity of different treatment modalities in deciduous teeth: an in vitro study
In recent years, different biotechnological materials and modalities
with antibacterial activity are being developed for oral cavity
disinfection. However, the antimicrobial effects of all these materials
have not been studied and understood in detail. Thus, the aim of this
study was to compare the antibacterial activity of ozone therapy with
dentine-bonding agents (containing antibacterial monomer
12-meth-acryloyloxydodecylpyridinium bromide (MDPB) and
10-methacryloyloxydecyl dihydrogen phosphate (MDP) and Ca(OH)(2) for
deciduous teeth in vitro. The antibacterial effectiveness of the studied
materials was determined by using a tooth cavity model on cylindrical
cavities created in 90 deciduous second mandibular molars. Streptococcus
mutans suspension was inoculated in the cavities. The teeth were
distributed into six study groups (five different modalities and a
negative control group). Dentine samples, which were collected from the
cavities before and after the treatment sessions, were microbiologically
evaluated and the materials' antibacterial activities were compared.
There were statistically significiant differences in the S. mutans
counts before and after treatment (P < 0.05). In terms of antibacterial
efficiency, 60-second O-3 treatment was found to be the most successful
method, followed by 30-second O-3, Clearfil Protect Bond (containing
MDPB), Clearfil SE Bond (containing MDP) and Ca(OH)(2) treatment. The
results from this study suggested that longer exposure to ozone might
have more beneficial effects in terms of antibacterial activity for
reducing the levels of S.mutans