18 research outputs found
Miniaturized Devices for Reaction Monitoring Using Online Mass Spectrometry and Developments Towards Reaction Control
Understanding the mechanism of chemical reactions brings possibilities to optimization of reaction conditions. Microreactors coupled online to mass spectrometric detection provide a system highly suitable for mechanistic studies, enabling sensitive, selective, and rapid detection. By combining the information obtained with this experimental system with theoretical density functional theory investigations of the potential energy surface of the system, detailed information about the mechanism of a reaction can be obtained. On the other hand, molecularly imprinted polymers are useful tools for facilitating selective synthesis. This is achieved by formation of cavities within the polymer matrix, which are able to stabilize the transition state of the desired reaction.
In this thesis, three different miniaturized reactors fabricated with additive manufacturing were combined online with electrospray ionization mass spectrometry for monitoring chemical reactions (Studies I-IV). The different miniaturized reactors were found to be variably suitable for this task. Overall, three different reactions were studied using miniaturized reactors coupled to a mass spectrometer – an inverse electron-demand Diels-Alder, followed by a retro Diels-Alder reaction (Studies I and II), an oxidation of a heptafulvene into the corresponding tropone by meta-chloroperoxybenzoic acid (Study III), and an acetylation reaction yielding the antibiotic drug linezolid (Study IV). The online mass spectrometry results obtained for the heptafulvene oxidation reaction were furthermore used as a basis for density functional theory studies of said reaction (Study III). Nine reaction pathways were investigated. The key step of the mechanism with the lowest energy barrier for oxidation of the studied heptafulvene into its corresponding tropone was identified as a Criegee-like rearrangement, while the overall reaction follows a Hock-like mechanism.
Furthermore, highly porous molecularly imprinted polymer systems, which in flow injection quartz crystal microbalance studies exhibited enantioselectivity for a proposed transition state analogue of a transamination reaction, were developed and assessed (Study V). The molecularly imprinted systems prepared with n-heptane as porogen, and polystyrene beads, which, when extracted out, formed pores in the polymers that were imprinted with a molecule having either a D or L conformation of a proposed transition state analogue of a transaminase reaction, showed a clear selectivity for the transition state analogue enantiomer that they were imprinted with in flow injection quartz crystal microbalance studies. Otherwise these systems exhibited similar selectivity for the other analytes screened.
The results presented in this thesis demonstrate that online combination of additively manufactured miniaturized reactors and mass spectrometry provides a convenient system for monitoring reactions online. At the same time, the results highlight limitations of the system such as memory effects arising from rough surfaces of the miniaturized reactors in combination with (from a mass spectrometry viewpoint) high concentrations of reactants used. However, the results from the oxidation study show that combinations of several methods can aid in overcoming limitations that one single approach may present. Finally, the developed hyperporous molecularly imprinted systems for enantioselective transamination reaction are promising for introduction into miniaturized reactors in the future.Förståelse av mekanismen för hur kemiska reaktioner sker möjliggör optimering av reaktionsförhållandena. Mikroreaktorer kopplade online (direkt) till masspektrometrisk detektion erbjuder ett experimentellt system som är väl lämpat för mekanistiska studier då det möjliggör sensitiv, selektiv och snabb detektion. Genom att kombinera informationen som fås med hjälp av detta experimentella system med teoretiska täthetsfuktionalteoretiska studier av den potentiella energiytan för systemet ifråga, kan detaljerad information om en reaktions mekanism erhållas. Molekylärt imprintade polymerer är, å andra sidan, användbara verktyg för att främja selektiv kemisk syntes. Den ökade selektiviteten för en syntes fås genom att selektiva ”fickor”, som har egenskaper som kan stabilisera den önskade reaktionens övergångstillstånd, skapas i en polymermatris.
I denna avhandling har tre miniatyriserade reaktorer, som tillverkats genom friformsframställning (3D printning), kombinerats online med masspektrometri för monitorering av kemiska reaktioner (Studie I-IV). De olika reaktorerna visade sig vara varierande lämpade för detta ändamål. Sammanlagt studerades tre reaktioner genom att koppla miniatyriserade reaktorer online till en masspektrometer – en inverst elektronbehovs-Diels-Alder, följd av en retro Diels-Alder reaktion (Studie I och II), en oxidering av en heptafulven till dess motsvarande tropon med hjälp av meta-kloroperoxybensoesyra (Studie III), och en acetyleringsreaktion för framställning av det antibiotiska läkemedlet linezolid (Studie IV). Masspektrometriresultaten för heptafulven-oxidationen användes som utgångspunkt för täthetsfuntionalteoristudier av reaktionens mekanism (Studie III). Nio reaktionsvägar undersöktes med denna metod. Nyckelsteget i mekanismen med lägst energibarriär för reaktionen fastställdes vara en Criegee-liknande omlagring, emedan den sammantagna mekanismen för oxidationen följer en Hock-liknande mekanism.
Vidare utvecklades och utvärderades hyperporösa molekylärt imprintade polymersystem, som i kvartskristallmikrovågsexperiment uppvisade enantioselektivitet för en föreslagen övergångstillståndsanalog i en transaminasreaktion (Studie V). De molekylärt imprintade systemen som förberetts med n-heptan som porogen och innehöll polystyrenkulor, som då de extraheras ut ur polymermatrisen, lämnar porer i polymeren som visade en tydlig selektivitet för övergångstillståndsanalog-enantiomeren som den imprintats med. För andra analyter uppvisade dessa system liknande selektivitet.
Resultaten som presenteras i denna avhandling visar att online-koppling av 3D printade miniatyriserade reaktorer till masspektrometri är ett användbart system för att följa kemiska reaktioner online. Samtidigt belyser resultaten att detta system har begränsningar, så som problem med minneseffekter av analyter i systemet, vilket uppkommer från reaktorernas ojämna ytor kombinerat med (från ett masspektrometriskt perspektiv) användning av höga koncentrationer av reaktanter. Dock visar resultaten från oxidationsstudien att kombinerande av flera olika metoder kan bidra till att kompensera för begränsningarna som en viss metod kan medföra. Slutligen så är de utvecklade hyperporösa molekylärt imprintade systemen för enantioselektiv transaminasreaktion lovande för framtida introducering i miniatyriserade reaktorer
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Nanoporous Quartz Crystal Microbalance: Increasing Sensitivity 1000x and Beyond
We report experimental results of the adsorption and desorption kinetics of 1-octadecanethiol onto porous gold quartz crystal microbalances (QCM). Fabricated porous gold substrates range in thickness from 75 nm to 3 µm. The porous gold was fabricated using a two-step process of sputtering and etching. First, an alloy of gold and silver was sputtered onto a flat gold QCM with the desired ratio of roughly 70 atomic percent silver and 30 atomic percent gold. Second, the sputtered silver from the alloy was removed by etching in concentrated nitric acid, leaving a gold nanoporous structure on the surface. This porous gold structure on the QCM surface greatly increases the surface area of the sensor, allowing much more thiol to be adsorbed. Experimental adsorption kinetics are compared to a Langmuir isotherm model. Thiol adsorption on porous QCM in n-Hexane is presented with concentrations ranging from 10nM (5ppb) to 3mM (900ppm). Thiol adsorption and kinetics on a nominally flat gold surface are included for comparison. Optimized sputtering conditions for porous gold substrates lead to a 1000-fold increase of thiol adsorption over flat gold QCM. It follows that the high specific area of porous gold can amplify the final sensitivity of a flat QCM by more than 3 orders of magnitude. We further present evidence that the three orders of magnitude sensitivity increase we achieve is the maximum enhancement possible when used in liquids for thiol detection. We verify our theoretical model of the QCM, describe our fabrication technique, characterize our substrates, and detail the uses of our porous gold QCM
PZE-transduced Suspended Microchannel Resonators for sensing applications
This PhD thesis aims at developing a system which can measure the mechanical properties of fluidic samples in the picoliter range. The ultimate goal is the characterization of cancer cells and viscoelastic fluids (i.e. biological fluids), in order to study their mass and stiffness for diagnostic applications.
The core of this project is the design, fabrication and characterization of hollow micromechanical resonators containing embedded microfluidic channels and provided with integrated piezoelectric (PZE) transduction. The measurement strategy consists in monitoring the device resonance frequency over time, while the analyte flows through the microchannel.
Arrays of singly-clamped and doubly-clamped resonators are made of low stress Silicon Nitride (ls-SiNx) and vibrate in a frequency range from tens of kHz to few MHz. Microfluidic channels span 25%, 60% and 100% of the cantilever length in order to compare the resonance frequency shift induced by the same particle at different positions, along identically-designed beams. The goal is to disentangle analyte mass and stiffness contribution from the suspended microchannel resonator (SMR) mechanical response. The cross section of the suspended fluidic channel, 6 um x 10 um, is designed to measure particles in the same size range (i.e. red blood cells or circulating tumor cells).
SMR energy dissipation is studied via FEM simulation, as a function of fluidic properties and geometrical dimensions. A coupled fluid-structure interaction (FSI) problem, based on linear elasticity and linearized Navier Stokes equations, is studied. The model is found well in agreement with theory and experiments presented in literature, considering the viscosity range of interest in case of biosensing application.
The fabrication of transparent and PZE-transduced suspended microchannel resonators is achieved via a 6-mask process flow. 250, 500, 750 and 1000 um long singly- and doubly-clamped SMRs are fabricated. Microfluidic channels are defined via the etching of high aspect ratio-trenches through a sacrificial layer of polysilicon, and filled with ls-SiNx. Discontinuous etch apertures are defined on top of the buried fluidic network and enable channel emptying in 25 minutes via KOH etching. PZE electrodes in platinum and aluminum nitride are deposited via sputter deposition and provide independent actuation and readout of each resonator, for the first time in SMR arrays.
The development of an experimental platform enables fluidic and electrical connections, as well as temperature control during devices characterization.
The mechanical response of fabricated sensors is measured in air and vacuum environment, while channels are filled with air, water and Isopropyl Alcohol. PZE electrodes demonstrate efficient actuation, in the order of 1.5 nm/V for 250 um- long singly-clamped SMRs. However, PZE detected signals result very low in amplitude, thus optical detection via laser Doppler vibrometer is preferred.
Frequency stability of fabricated sensors is studied in order to estimate their sensing performances and characterize their physical limitations. 250 um-long SMRs filled with DI water exhibit a frequency stability of 30 ppb at 400 ms integration time, in air. This result is in agreement with values found in literature for SMRs sensors and translates in an estimated mass sensitivity of few femtograms
Microfluidics for Biosensing
There are 12 papers published with 8 research articles, 3 review articles and 1 perspective. The topics cover: Biomedical microfluidics Lab-on-a-chip Miniaturized systems for chemistry and life science (MicroTAS) Biosensor development and characteristics Imaging and other detection technologies Imaging and signal processing Point-of-care testing microdevices Food and water quality testing and control We hope this collection could promote the development of microfluidics and point-of-care testing (POCT) devices for biosensing
Graphene resonators for mass sensing applications
PhD ThesisGraphene’s exceptional physical and mechanical properties make it an excellent
nanomaterial for MEMS/NEMS devices with wide reaching applications. This
thesis explores graphene as a nanomaterial, its use in mass sensing applications
and the suitability of existing theoretical models to describe its behaviour as a
rectangular resonator. Several local and nonlocal continuum models have been
proposed in literature for the vibration analysis of graphene resonators. But with
very little experimental data to validate these theoretical models, most of the
solutions employed to solve these models compare their results with results from
other theoretical models, leading to doubts about their validity and accuracy. In
addition to providing a guide for determining the suitable theoretical model for
different sized rectangular graphene resonators, this work establishes that a
small-scale parameter 0 of any value between 0 and 2 needs to be
incorporated in any local continuum modelled applied to micro-sized graphene
sheets to avoid overestimation of the frequency of the sheets. A fabrication route
for NEMS and MEMS devices with rectangular graphene resonators up to 32
by 7 is also developed with the provision for magnetomotive actuation via
Lorentz force with possible capacitive readout capabilities. This is important as
the use of graphene in MEMS/NEMS is being hurriedly transitioned from the
Research space to the marketplace
Microelectromechanical Systems and Devices
The advances of microelectromechanical systems (MEMS) and devices have been instrumental in the demonstration of new devices and applications, and even in the creation of new fields of research and development: bioMEMS, actuators, microfluidic devices, RF and optical MEMS. Experience indicates a need for MEMS book covering these materials as well as the most important process steps in bulk micro-machining and modeling. We are very pleased to present this book that contains 18 chapters, written by the experts in the field of MEMS. These chapters are groups into four broad sections of BioMEMS Devices, MEMS characterization and micromachining, RF and Optical MEMS, and MEMS based Actuators. The book starts with the emerging field of bioMEMS, including MEMS coil for retinal prostheses, DNA extraction by micro/bio-fluidics devices and acoustic biosensors. MEMS characterization, micromachining, macromodels, RF and Optical MEMS switches are discussed in next sections. The book concludes with the emphasis on MEMS based actuators
Self-powered mobile sensor for in-pipe potable water quality monitoring
Traditional stationary sensors for potable-water quality monitoring in a wireless sensor network format allow for
continuous data collection and transfer. These stationary sensors have played a key role in reporting contamination
events in order to secure public health. We are developing a self-powered mobile sensor that can move with the water flow, allowing real-time detection of contamination in water distribution pipes, with a higher temporal resolution. Functionality of the mobile sensor was tested for detecting and monitoring pH, Ca2+, Mg2+, HCO3-/CO32-, NH4+, and Clions. Moreover, energy harvest and wireless data transmission capabilities are being designed for the mobile sensor
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Smart Platform for Low-Cost MEMS Sensors – Pressure, Flow and Thermal Conductivity
In a technological world that is trending towards smart and autonomous engineering, the collection of quality data is of unrivalled importance. This has led to a huge market demand for the development of low-cost, small and accurate sensors and thus has resulted in significant research into sensors, with the aim of advancing the price/performance ratio in commercial solutions. Micro Electro Mechanical Systems (MEMS) have recently offered an attractive solution to miniaturise and drastically improve the performance of sensors. In this thesis, MEMS technology is exploited to create a multi-sensor technology platform that is used to fabricate several sensing technologies.
Piezo-resistive and piezo-electronic pressure sensors are designed, fabricated and tested. Different doping profiles, stress-engineered structures and electronic devices for pressure transduction are investigated, with focus on their sensitivity and non-linearity. A ring is fabricated in the metal layer around the circumference of the membrane that alleviates the effects of over/under etching. This is achieved by creating a new rigid edge of the membrane in the metal layer, which has tighter fabrication tolerances. A piezo-MOSFET is developed and shown to have greater sensitivity than similar state-of-the-art devices.
Flow sensors based on a heated tungsten wire are designed, fabricated, tested and substantiated with numerical modelling. Calorimetric and anemometric driving modes are optimised with regards to device structure. Thermodiodes are also used as the temperature transduction devices and are compared to the traditional resistor method and showed to be preferable when further miniaturising the sensor.
Thermal conductivity gas sensors based on a heated tungsten resistor are designed, tested and substantiated with numerical modelling. Holes through the membrane are used to improve the sensitivity to measuring carbon dioxide by 270%. Asymmetric holes are utilised to prove a novel method of measuring thermal conductivity in a calorimetric method. Designs improving this new concept are outlined and substantiated with analytical and numerical models.
Linear statistical methods and artificial neural networks are used to differentiate flow rate and gas concentration using three on-membrane resistors. With membrane holes, the discrimination between gases in the presence of flow is improved. Neural networks provide a viable solution and show an increase in the accuracy of both flow rate and gas concentration.
The main objective of the work in this thesis was to develop low-cost, low-power, small devices capable of high-volume production and monolithic integration using a single smart technology platform for fabrication. The smart technology platform was used to create pressure sensors, flow sensors and thermal conductivity gas sensors. Within each sensing technology, proof-of-concepts and optimisations have been carried out in order to maximise performance whilst using the low-cost, high-volume fabrication process, ultimately helping towards smart and autonomous engineering solutions driven by data