Vertical-external-cavity surface-emitting lasers and quantum dot lasers

The use of cavity to manipulate photon emission of quantum dots (QDs) has been opening unprecedented opportunities for realizing quantum functional nanophotonic devices and also quantum information devices. In particular, in the field of semiconductor lasers, QDs were introduced as a superior alternative to quantum wells to suppress the temperature dependence of the threshold current in vertical-external-cavity surface-emitting lasers (VECSELs). In this work, a review of properties and development of semiconductor VECSEL devices and QD laser devices is given. Based on the features of VECSEL devices, the main emphasis is put on the recent development of technological approach on semiconductor QD VECSELs. Then, from the viewpoint of both single QD nanolaser and cavity quantum electrodynamics (QED), a single-QD-cavity system resulting from the strong coupling of QD cavity is presented. A difference of this review from the other existing works on semiconductor VECSEL devices is that we will cover both the fundamental aspects and technological approaches of QD VECSEL devices. And lastly, the presented review here has provided a deep insight into useful guideline for the development of QD VECSEL technology and future quantum functional nanophotonic devices and monolithic photonic integrated circuits (MPhICs).Comment: 21 pages, 4 figures. arXiv admin note: text overlap with arXiv:0904.369

Development of an On-Animal Separation Based Sensor using On-line Microdialysis Sampling Coupled to Microchip Electrophoresis with Electrochemical Detection

Microdialysis is a sampling technique that can be employed for the continuous monitoring of compounds both in vivo and in vitro. The online-coupling of microdialysis to microchip electrophoresis provides an attractive technology for near real time monitoring of drugs and neurotransmitters in pharmacokinetic and behavioral studies. These on-line systems for the analysis of microdialysis samples allow for the development of selective and sensitive separation based sensors with the capability of preserving high temporal resolution. Electrochemical detection is well suited for these separation-based sensors due to the possibility of integrating the working and reference electrodes directly into the chip as well as the availability of a miniaturized isolated potentiostat. This dissertation primarily focuses on the development of an on-animal separation-based sensor using microdialysis coupled to microchip electrophoresis with amperometric detection. The system consists of an on-line interface to couple the microdialysis to microchip electrophoresis, high voltage power supplies, and an electrically isolated potentiostat. Initial studies were focused on developing and fabricating an all glass microfluidic device. This system was evaluated in vitro for the continuous monitoring of the enzymatic production of hydrogen peroxide. The system was optimized for the in vivo analysis of nitrite on a freely roaming animal. The system incorporates telemetry for remote control, data acquisition, and has been optimized for the continuous on-line analysis of microdialysis samples obtained using a linear probe following nitroglycerin administration. The on-line microdialysis-microchip electrophoresis system was fabricated using an all glass substrate that includes an electrophoresis separation channel, integrated platinum working and reference electrodes, as well as an interface for direct coupling of the chip to the microdialysis probe. This dissertation describes the development of the integrated system including optimization of the electrophoresis conditions, injection of samples into the chip using the on-line microdialysis-microchip electrophoresis interface, and evaluation of the overall ruggedness of the system. The ultimate goal is to use the separation based sensor for on-animal in vivo analysis of drugs and neurotransmitters in order to correlate neurochemistry and/or metabolism with behavior in freely roaming animals

High-throughput microfluidic assay devices for culturing of soybean and microalgae and microfluidic electrophoretic ion nutrient sensor

In the past decade, there are significant challenges in agriculture because of the rapidly growing global population. Meanwhile, microfluidic devices or lab-on-a-chip devices, which are a set of micro-structure etch or molded into glass, silicon wafer, PDMS, or other materials, have been rapidly developed to achieve features, such as mix, separate, sort, sense, and control biochemical environment. The advantages of microfluidic technologies include high-throughput, low cost, precision control, and highly sensitive. In particular, they have offered promising potential for applications in medical diagnosis, drug discovery, and gene sequencing. However, the potential of microfluidic technologies for application in agriculture is far from being developed. This thesis focuses on the application of microfluidic technologies in agriculture. In this thesis, three different types of microfluidic systems were developed to present three approaches in agriculture investigation. Firstly, this report a high throughput approach to build a steady-state discrete relative humidity gradient using a modified multi-well plate. The customized device was applied to generate a set of humidity conditions to study the plant-pathogen interaction for two types of soybean beans, Williams and Williams 82. Next, a microfluidic microalgal bioreactor is presented to culture and screen microalgae strains growth under a set of CO2 concentration conditions. C. reinhardtii strains CC620 were cultured and screened in the customized bioreactor to validate the workability of the system. Growth rates of the cultured strain cells were analyzed under different CO2 concentrations. In addition, a multi-well-plate-based microalgal bioreactor array was also developed to do long-term culturing and screening. This work showed a promising microfluidic bioreactor for in-line screening based on microalgal culture under different CO2 concentrations. Finally, this report presents a microchip sensor system for ions separation and detection basing electrophoresis. It is a system owning high potential in various ions concentration analysis with high specificity and sensitivity. In addition, a solution sampling system was developed to extract solution from the soil. All those presented technologies not only have advantages including high-throughput, low cost, and highly sensitive but also have good extensibility and robustness. With a simple modification, those technologies can be expanded to different application areas due to experimental purposes. Thus, those presented microfluidic technologies provide new approaches and powerful tools in agriculture investigation. Furthermore, they have great potential to accelerate the development of agriculture

A microfluidic bacteria culturing device with MALDI mass spectrometry detection

A novel microfluidic device was developed for bacterial cell culturing using mass spectrometry as the detector. One of the challenges in proteomics is to achieve high sensitivity in the identification of proteins in complex samples with widely varying concentrations. The main limitations for proteomic studies are relatively slow and labor-intensive steps such as cell culturing and protein digestion of small sample quantities. Microfluidics is a promising approach to increase throughput and to reduce the time-consuming steps that are necessary for proteomics. When an analytical detection method is combined with microfluidics it can overcome limitations that are important in the analysis of biological samples. In this work a microfluidic device was constructed from poly(methyl methacrylate) PMMA using hot embossing from a brass metal mold prepared from micro-milling and combined with off-line matrix assisted laser desorption-mass spectrometry mass spectrometry (MALDI-MS) for analysis. In this work, E. coli K12 strain was selected as a model for performing the analysis. Microfluidic devices were used to process the sample and mass spectrometry was used as detection method. The microfluidic device used in this study consists of three modules, capture, culture, and digestion chamber, integrated onto a single platform. The cells are captured on the microfluidic chip using polyclonal goat antibody on a modified PMMA surface, and are released using 0.25% trypsin, and transferred to the culture cell, which is filled with the growth medium. The temperature of the culture cell is maintained at 37 ºC using a heater and a PDMS cover slip was used for air perfusion. Samples collected at different culturing durations (4 h, and 10 h) are transferred to a micro-post bioreactor, which contains immobilized trypsin. The effluent from the microfluidic device was spotted onto a MALDI target and analyzed using MALDI time-of-flight mass spectrometry

Microfluidic devices interfaced to matrix-assisted laser desorption/ionization mass spectrometry for proteomics

Microfluidic interfaces were developed for off-line matrix-assisted laser desorption/ionization mass spectrometry (MALDI). Microfluidic interfaces allow samples to be manipulated on-chip and deposited onto a MALDI target plate for analysis. For this research, microfluidic culturing devices and automated digestion and deposition microfluidic chip platforms were developed for the identification of proteins. The microfluidic chip components were fabricated on a poly(methyl methacrylate), PMMA, wafer using the hot embossing method and a molding tool with structures prepared via micromilling. One of the most important components of the chip system was a trypsin microreactor. An open channel microreactor was constructed in a 100 µm wide and 100 µm deep channel with a 4 cm effective channel length. This device integrated frequently repeated steps for MALDI-based proteomics such as digestion, mixing with a matrix solution, and depositing onto a MALDI target. The microreactor provided efficient digestion of proteins at a flow rate of 1 µL/min with a residence time of approximately 24 s in the reaction channel. An electrokinetically driven microreactor was also developed using a micropost structured chip for digestion. The micropost chip had a higher digestion efficiency due to the higher surface area-to-volume ratio in the channel. Also, the electrokinetic flow eliminated the need for an external pumping system and gave a flat flow profile in the microchannel. The post microreactor consisted of a 4 cm × 200 µm × 50 µm microfluidic channel with trypsin immobilized on an array of 50 µm in diameter micropost support structures with a 50 µm edge-to-edge inter-post spacing. This micropost reactor was also used for fingerprint analysis of whole bacterial cells. The entire tryptic digestion and deposition procedure for intact bacteria took about 1 min. A contact deposition solid-phase bioreactor coupled with MALDI-TOF MS allowed for low-volume fraction deposition with a smaller spot size and a higher local concentration of the analyte. A bacterial cell-culturing chip was constructed for growing cells on-chip followed by off-line MALDI analysis. Coupling MALDI-TOF MS whole cell analysis with microfluidic culturing resulted in more consistent spectra as well as reduction of the total processing time. The microfluidic cell culturing was performed in a PMMA chip with a polydimethylsiloxane (PDMS) cover to allow gas permeation into the culture channel, which contained a 2.1 μL volume active culture chamber. After incubation of E. coli in a microfluidic culture device at 37 ℃ for 24 h, the cultured cells were analyzed with MALDI MS. Also, a microfluidic cell culture device containing continuous perfusion of culture medium was developed using a polycarbonate membrane. This microfluidic culturing format was improved with a fluidic manifold and thermostatted microheaters. Fingerprint mass spectra distinguishing E. coli strains tested were obtained after a 6 h incubation time, which was shorter compared to the 24 h incubation time using conventional culturing techniques. In addition, an enhanced identification procedure for bacteria was achieved by integrating on-chip digestion of cultured bacteria

Development of Microfluidic Devices Incorporating Electrochemical Detection

Neurological disorders affect millions of people worldwide every day. These disorders range from issues affecting mental health, like depression to degenerative diseases such as Alzheimer's and Parkinson's disease. The neurotransmitters dopamine and nitric oxide are of particular interest. Incorrect regulation of dopamine has been implicated in disorders such as depression, obsessive compulsive disorder, and attention deficit disorder as well as neurological degenerative diseases such as Parkinson's and Alzheimer's. Nitric oxide (NO) has been shown to affect sexual behavior and aggression in rats. NO has been identified as not just a neurotransmitter but also a neuromodulator and is associated with oxidative stress resulting in neurodegeneration. This small gaseous molecule has a short physiological half-life, so nitrite is commonly used for the indirect detection of nitric oxide. In order to study neurological disorders methods often reduce or eliminate the in vivo concentrations of a compound of interest in order to determine its behavioral effect. However, dopamine and NO have complex metabolic pathways and functions, so the resulting behavior may be due to a series of chemical changes in the brain. In order to fully understand how these two neurotransmitters affect behavior both the in vivo concentration of multiple analytes and behavior need to be monitored simultaneously. In this thesis, the development of a small and simple microchip electrophoresis device that can be used as a component of a portable analysis system, which is capable of functioning on an awake and freely moving animal, is described. The development of low cost polymer microchip electrophoresis (ME) devices capable of interfacing with microdialysis (MD) sampling with electrochemical (EC) detection for the determination of dopamine and nitrite is described. Different fabrication processes were evaluated and optimized to create low cost polymer microchips. A polydimethylsiloxane (PDMS)/glass hybrid microchip capable of interfacing with the hydrodynamic flow from an on-line microdialysis probe was developed with an integrated carbon electrode for EC detection and used for the detection of nitrite. This microchip failed to inject sample into the separation channel when the conductivities of the sample and the BGE were significantly different. In order to understand the injection failure a finite element modeling program, COMSOL, was employed to simulate the sample injection method used for the PDMS/glass hybrid microchip. Also, a new microchip electrophoresis device, called a bow microchip, capable of injecting high conductivity samples while using a low conductivity BGE for electrophoretic separation was modeled. That bow microchip was then evaluated experimentally and made possible the injection of a plug of artificial cerebral spinal fluid into a separation channel containing low conductivity BGE. In addition to the microchip fabrication and optimization, a graphite/polymethylmethacrylate (PMMA) composite electrode was developed and optimized. This electrode was integrated into a polymer substrate for EC detection and evaluated by both flowinjection analysis and microchip electrophoresis. Future directions include the further optimization of the bow microchip design to simplify the operation and increase the functionality of the microchip. Also, the addition of ionic liquids, which may increase the electron transfer rate, to the graphite/PMMA composite electrode (GPCE) and the use of electrode arrays, which should increase the signal without significantly increasing the background noise, may lower the limits of detection

MODERNIZATION OF THE MOCK CIRCULATORY LOOP: ADVANCED PHYSICAL MODELING, HIGH PERFORMANCE HARDWARE, AND INCORPORATION OF ANATOMICAL MODELS

A systemic mock circulatory loop plays a pivotal role as the in vitro assessment tool for left heart medical devices. The standard design employed by many research groups dates to the early 1970\u27s, and lacks the acuity needed for the advanced device designs currently being explored. The necessity to update the architecture of this in vitro tool has become apparent as the historical design fails to deliver the performance needed to simulate conditions and events that have been clinically identified as challenges for future device designs. In order to appropriately deliver the testing solution needed, a comprehensive evaluation of the functionality demanded must be understood. The resulting system is a fully automated systemic mock circulatory loop, inclusive of anatomical geometries at critical flow sections, and accompanying software tools to execute precise investigations of cardiac device performance. Delivering this complete testing solution will be achieved through three research aims: (1) Utilization of advanced physical modeling tools to develop a high fidelity computational model of the in vitro system. This model will enable control design of the logic that will govern the in vitro actuators, allow experimental settings to be evaluated prior to execution in the mock circulatory loop, and determination of system settings that replicate clinical patient data. (2) Deployment of a fully automated mock circulatory loop that allows for runtime control of all the settings needed to appropriately construct the conditions of interest. It is essential that the system is able to change set point on the fly; simulation of cardiovascular dynamics and event sequences require this functionality. The robustness of an automated system with incorporated closed loop control logic yields a mock circulatory loop with excellent reproducibility, which is essential for effective device evaluation. (3) Incorporating anatomical geometry at the critical device interfaces; ascending aorta and left atrium. These anatomies represent complex shapes; the flows present in these sections are complex and greatly affect device performance. Increasing the fidelity of the local flow fields at these interfaces delivers a more accurate representation of the device performance in vivo

A novel microfluidic enrichment technique for carbonylated proteins

Proteins are the building blocks of cells in living organisms, and are composed of amino acids. The expression of proteins is regulated by the processes of transcription and translation. Proteins undergo post-translational modifications in order to dictate their role physiologically within a cell. Not all post-translational modifications are beneficial for the protein or the cell. One type of post-translational modification, called carbonylation, irreversibly places a carbonyl group onto an amino acid residue, most commonly proline, lysine, arginine, and threonine. This modification can have severe consequences physiologically, including loss of solubility, loss of function, and protein aggregation. Carbonylated proteins have commonly been used as a marker of oxidative stress. Oxidative stress has been suggested to play a role in many human disease states, such as Alzheimer\u27s Disease, Amyotrophic Lateral Sclerosis, Parkinson\u27s Disease, inflammatory diseases, and others. Evidence shows oxidative stress to be a contributing factor in the progression of aging. Therefore, markers of oxidative stress, such as carbonylated proteins, can provide key information for the development of valuable therapeutics for these conditions. However, they are found in low abundance in samples and require enrichment prior to proteomic-based studies. Currently, affinity chromatography is the chosen method for enriching carbonylated proteins in a sample. However, the technique has significant drawbacks, including a large sample requirement, a large time requirement, the need for derivatization, and a high dilution of the sample post elution. This dissertation introduces a microfluidic enrichment technique for carbonylated proteins. The technique involves the surface modification of a polymer microchip for selective capture of carbonylated proteins. The surface chemistry is verified using different analytical techniques. Specificity of the target molecule\u27s capture is demonstrated using a native protein. The capture conditions are optimized experimentally by studying four unique variables. Lastly, theoretical modeling is performed to determine the conditions that would lead to the technique\u27s failure. It is seen that the technique can selectively capture target proteins from a flowing solution, even in the presence of an unoxidized protein. Protein capture is most dependent upon flow rate and crosslinker concentration. The flow rates required to break the bonds formed between an oxidized protein and the crosslinker exceeds feasible levels within a microfluidic channel. The microfluidic enrichment technique provides a promising alternative to the current gold standard of avidin affinity chromatography. The device has promise as a possible protein biomarker discovery tool in the search for therapeutic targets in human disease states where oxidative stress has been implicated

Stabilization techniques and silicon-germanium saturable absorbers for high repetition rate mode-locked lasers

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.Includes bibliographical references (p. 163-176).The monolithic integration of passively mode-locked solid-state lasers at highest repetition rates has been prevented by Q-switching instabilities and the lack of integrable saturable absorbers to date. In this thesis we demonstrate in theory and experiment that active feedback electronics controlling the intracavity loss of the laser is capable of suppressing the Q-switching instability. We introduce a control system's perspective to the stability of saturable absorber mode-locked lasers. This approach unifies the existing methods of laser stabilization and identifies feedback control with an intracavity loss modulator as a universal stabilization scheme, applicable without restrictions to lasers at the highest repetition rates. This finding is validated in laboratory experiments by showing that a laser which is unstable without feedback control can reach a noise performance equivalent to that of a, passively stabilized laser, once the feedback controller is engaged. The addition of feedback stabilization does not negatively affect the pulse shaping dynamics, since controller and mode-locking dynamics occur on vastly different timescales. Furthermore, we address the materials challenge of manufacturing a CMOS-compatible saturable Bragg reflector in the Si-SiO2-Ge materials system, enabling the monolithic integration of the absorber with the laser gain medium of future compact mode-locked lasers. A wafer-scale Si-SiO2 high reflector with 99.8% peak reflectance and an unprecedented bandwidth of 700 nm in the near-infrared serves as the substrate of a saturable Bragg reflector, while a germanium layer grown on top provides saturable loss.(cont.) Ultrafast recovery of the saturation is observed in pump-probe measurements, indicating the operation of the saturable Bragg reflector as a fast semiconductor saturable absorber in the laser. In contrast, strong inverse saturable loss occurs in the regime of high fluence, contributing to stabilization against Q-switching instabilities. An erbium-ytterbium:glass laser mode-locked with the silicon-germanium saturable Bragg reflector generates the shortest pulse and broadest optical spectrum obtained from a bulk Er-Yb:glass laser to date. Spanning the C-band of optical communications on a ±10 dB level, it demonstrates that mode-locked Er-Yb:glass lasers can serve as multi-wavelength laser sources in next-generation optical communications systems, providing all channels across the communications spectrum with a stable train of pulses.by Felix Jan. Grawert.Ph.D