Aggregation-induced emission (AIE) dye loaded polymer nanoparticles for gene silencing in pancreatic cancer and their in vitro and in vivo biocompatibility evaluation

We have developed aggregation-induced emission (AIE) dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration (FDA) approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction (PCR) indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research

Engineering functional nanomaterials for biophotonics and nanomedicine applications

To date, functional nanomaterials have been commonly synthesized and applied for various biomedical applications such as sensing, imaging, drug delivery, and tissue engineering due to their unique optical, electronic, and biocompatible property. In this Ph.D. work, different types of nanomaterials/nanodevices have been engineered, characterized, and studied for biophotonic sensing and nanodrug delivery therapy, namely, two-dimensional (2D) transition metal dichalcogenides (TMDCs), nanoporous polymers and triboelectric nanogenerator (TENG). The engineered solutions presented in the Thesis aims at addressing current limitations in healthcare diagnostics and therapeutics fields, particularly the low detection sensitivity of optical biosensors and the large footprint of stimuli-controlled drug delivery systems. The presentation of this Thesis work was divided into two parts. In the first part of Thesis, we studied the physical and optical property of a series of 2D TMDCs including molybdenum disulfide (MoS2), tungsten disulfide (WS2), molybdenum diselenide (MoSe2) and tungsten diselenide (WSe2), to develop and optimize next generation of plasmonic biosensors with high sensitivity for small molecules. The sensing performance is affected by types of 2D materials, thickness and incident wavelength. In theoretical studies, a monolayer WS2 based plasmonic biosensor was demonstrated to achieve a 200% increment in the detection sensitivity in the visible wavelength. In the experimental studies, the phase sensitivity of the WS2 sensing film reaches 15,000 deg/RIU in detecting low concentration analytes, which represents an enhancement of 151% over the conventional bare gold SPR sensing film. In addition, the enhanced SPR biosensor exhibits fast and accurate feedback in real-time monitoring of small molecules. In the second part of the work, we designed and studied the triboelectric nanogenerator (TENG) in creating a miniaturized, self-powered drug delivery device for transdermal patch application. TENG system can effectively convert various mechanical energies into electricity. It has many advantages such as the large output of power, low cost, simple fabrication, and high conversion efficiency. The designed transdermal patch mainly composed of an electric-responsive polymer and TENG. The drugs embedded in the polymer matrix were released upon receiving electric-stimuli from TENG. Such a mechanism can allow one to achieve precise control in programming the drug delivery profile by tailoring the appropriate TENG action time. The release rate can be tuned from ~ 0.05 to 0.25 μg/cm2. More importantly, the drug delivery efficiency in dermis was noted to improve by ~ 100% when compared with the absence of TENG triggered reaction. In conclusion, this Ph.D. work has generated reliable and emerging engineering solutions to overcome challenges we faced in the current healthcare diagnostic and therapeutic technology especially in the areas of optical plasmonic sensors and skin patch drug delivery devices. Such solutions can be further integrated into other sensing and drug delivery systems for personalized healthcare applications.Doctor of Philosoph

A Novel, Finite-Time, Active Fault-Tolerant Control Framework for Autonomous Surface Vehicle with Guaranteed Performance

In this paper, a finite-time, active fault-tolerant control (AFTC) scheme is proposed for a class of autonomous surface vehicles (ASVs) with component faults. The designed AFTC framework is based on an integrated design of fault detection (FD), fault estimation (FE), and controller reconfiguration. First, a nominal controller based on the Barrier Lyapunov function is presented, which guarantees that the tracking error converges to the predefined performance constraints within a settling time. Then, a performance-based monitoring function with low complexity is designed to supervise the tracking behaviors and detect the fault. Different from existing results where the fault is bounded by a known scalar, the FE in this study is implemented by a finite-time estimator without requiring any prioir information of fault. Furthermore, under the proposed finite-time AFTC scheme, both the transient and steady-state performance of the ASV can be guaranteed regardless of the occurrence of faults. Finally, a simulation example on CyberShip II is given to confirm the effectiveness of the proposed AFTC method

Advanced low‐dimensional carbon materials for flexible devices

We live in a digitized era, where we are completely surrounded by a plethora of automated electronic systems, be it a smart home energy controller or a self‐operated diagnostic kiosk in a clinic. With the recent advent of one‐dimensional (1D) and two‐dimensional (2D) nanomaterials like carbon nanotube (CNT) and graphene, the world of electronics has revolutionized with state‐of‐the‐art product paradigms. These nanomaterials possess desirable features of large surface area, excellent electrical conductivity, and high mechanical strength. Electronic devices made out of these materials have the added advantages of being flexible, light‐weight, and durable. Thus, present‐day devices that utilize these substances as channel or electrode materials have been able to undergo a positive transformation as compared with conventional structures. Flexibility and bendability are some of the coveted aesthetics of modern‐day electronics and the use of these 1D and 2D nanomaterials imparts such features to the devices, without having to compromise on key output characteristics like sensitivity and efficiency. In this short review, we discuss about various new configurations that are based on graphene, CNT, and other materials like transition metal dichalcogenides, and how these materials have been able to metamorphose the attributes of conventional devices.NRF (Natl Research Foundation, S’pore)Published versio

Sensitivity enhancement of MoS2 nanosheet based surface plasmon resonance biosensor

A surface plasmon resonance based biosensor consisting of SF10 prism, silicon layer, gold thin film and MoS2 enhanced nanosheet is presented. We systematically investigated the SPR reflectivity and resonance angle through the transfer matrix method. Furthermore, with the optimized thickness of gold, silicon and MoS2, we calculated the change of resonance angle to a fixed refractive index change of sample solutions and the full width at half maximum of the reflectivity curves. The excitaition wavelengths of light sources that we use range from 600 nm to 1024 nm which covers both visible and near infrared light. In addition, the optimum configuration for MoS2-enhanced SPR biosensors are monolayer MoS2 and 7 nm silicon layer coated on 50 nm Au thin film with 633 nm as the excitation wavelength. With these optimized parameters we can efficiently increase the sensitivity by ∼10%. Even without the silicon layers, the pure MoS2 enhanced nanosheet can also improve the sensitivity by ∼8%. The performance of MoS2 enhanced nanosheet is almost 3-fold higher than that of graphene.Published versio

Giant enhancement in Goos-Hänchen shift at the singular phase of a nanophotonic cavity

In this letter, we experimentally demonstrate thirtyfold enhancement in Goos-Hänchen shift at the Brewster angle of a nanophotonic cavity that operates at the wavelength of 632.8 nm. In particular, the point-of-darkness and the singular phase are achieved using a four-layered metal-dielectric-dielectric-metal asymmetric Fabry-Perot cavity. A highly absorbing ultra-thin layer of germanium in the stack gives rise to the singular phase and the enhanced Goos-Hänchen shift at the point-of-darkness. The obtained giant Goos-Hänchen shift in the lithography-free nanophotonic cavity could enable many intriguing applications including cost-effective label-free biosensors.MOE (Min. of Education, S’pore)Published versio

Electrically tunable singular phase and Goos–Hänchen shifts in phase-change-material-based thin-film coatings as optical absorbers

The change of the phase of light under the evolution of a nanomaterial with time is a promising new research direction. A phenomenon directly related to the sudden phase change of light is the Goos-Hänchen (G-H) shift, which describes the lateral beam displacement of the reflected light from the interface of two media when the angles of incidence are close to the total internal reflection angle or Brewster angle. Here, an innovative design of lithography-free nanophotonic cavities to realize electrically tunable G-H shifts at the singular phase of light in the visible wavelengths is reported. Reversible electrical tuning of phase and G-H shifts is experimentally demonstrated using a microheater integrated optical cavity consisting of a dielectric film on an absorbing substrate through a Joule heating mechanism. In particular, an enhanced G-H shift of 110 times of the operating wavelength at the Brewster angle of the thin-film cavity is reported. More importantly, electrically tunable G-H shifts are demonstrated by exploiting the significant tunable phase change that occurs at the Brewster angles, due to the small temperature-induced refractive index changes of the dielectric film. Realizing efficient electrically tunable G-H shifts with miniaturized heaters will extend the research scope of the G-H shift phenomenon and its applications.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)National Research Foundation (NRF)Accepted versionK.V.S. and R.S. acknowledge the funding support from Singapore Ministry of Education (MOE) grant numbers AcRF MOE2016-T3-1-006 and MOE AcRF Tier 1 RG96/19 and Advanced Manufacturing and Engineering (AME) Programmatic grant (A18A5b0056) by Agency for Science, Technology and Research (A*STAR). R.M. and R.S.R. would like to acknowledge the Ministry of Education (MOE) through Tier 2 grants (2019-T2-1-058). In addition, C.M.D. and K.T.Y. acknowledge the funding support from Singapore National Research Foundation (NRF) and French National Research Agency (ANR), grant number (NRF2017-ANR002 2DPS)

Large-Area Silver-Stibnite Nanoporous Plasmonic Films for Label-Free Biosensing

The development of various plasmonic nanoporous materials has attracted much interest in different areas of research including bioengineering and biosensing because of their large surface area and versatile porous structure. Here, we introduce a novel technique for fabricating silver–stibnite nanoporous plasmonic films. Unlike conventional techniques that are usually used to fabricate nanoporous plasmonic films, we use a room-temperature growth method that is wet-chemistry free, which enables wafer-scale fabrication of nanoporous films on flexible substrates. We show the existence of propagating surface plasmon polaritons in nanoporous films and demonstrate the extreme bulk refractive index sensitivity of the films using the Goos–Hänchen shift interrogation scheme. In the proof-of-concept biosensing experiments, we functionalize the nanoporous films with biotin-thiol using a modified functionalization technique, to capture streptavidin. The fractal nature of the films increases the overlap between the local field and the immobilized biomolecules. The extreme sensitivity of the Goos–Hänchen shift allows femtomolar concentrations of streptavidin to be detected in real time, which is unprecedented using surface plasmons excited via the Kretschmann configuration

Sensitivity Enhancement of Transition Metal Dichalcogenides/Silicon Nanostructure-based Surface Plasmon Resonance Biosensor

In this work, we designed a sensitivity-enhanced surface plasmon resonance biosensor structure based on silicon nanosheet and two-dimensional transition metal dichalcogenides. This configuration contains six components: SF10 triangular prism, gold thin film, silicon nanosheet, two-dimensional MoS2/MoSe2/WS2/WSe2 (defined as MX2) layers, biomolecular analyte layer and sensing medium. The minimum reflectivity, sensitivity as well as the Full Width at Half Maximum of SPR curve are systematically examined by using Fresnel equations and the transfer matrix method in the visible and near infrared wavelength range (600 nm to 1024 nm). The variation of the minimum reflectivity and the change in resonance angle as the function of the number of MX2 layers are presented respectively. The results show that silicon nanosheet and MX2 layers can be served as effective light absorption medium. Under resonance conditions, the electrons in these additional dielectric layers can be transferred to the surface of gold thin film. All silicon-MX2 enhanced sensing models show much better performance than that of the conventional sensing scheme where pure Au thin film is used, the highest sensitivity can be achieved by employing 600 nm excitation light wavelength with 35 nm gold thin film and 7 nm thickness silicon nanosheet coated with monolayer WS2.Published versio