High sensitivity field asymmetric ion mobility spectrometer

Mario Andres Chavarria Varon
EPFL, 2016
Thèse EPFL

Résumé

Field Asymmetric IonMobility Spectrometry (FAIMS) is a very promising technique for chemical detection. FAIMS systems are portable, highly sensitive, relatively inexpensive and can work at atmospheric conditions. These attributes make it a very desirable technique to replace current bulky and expensive detection systems, such as Mass Spectrometry devices, especially for on-site experiments. Therefore, this work focuses on improving the FAIMS limits of detection (LoD) in order to expand the application fields for FAIMS technology. With this aim, the different factors affecting the FAIMS sensitivity and resolution were analyzed by theoretical and experimental studies. An ion mobility simulation software was developed based on the physical models for FAIMS proposed in literature. This software is able to simulate the ion trajectories inside the ion filter and the expected ion spectra, making it an important tool for theoretically determining the effect of different parameters in FAIMS measurements. It also helps the user to predict and understand the experimental results. The possibility of improving the fabrication process was evaluated by implementing two different techniques: PCB manufacturing and screen printing. The PCB plates were fabricated on FR4 substrates with copper electrodes while the screen printed plates used alumina substrates and silver-palladium electrodes. The prototypes developed with PCB techniques showed a very similar behavior to the standard alumina systems. Therefore, the PCB fabrication approach is a good option to reduce the fabrication complexity and costs of the FAIMS devices. Two atmospheric pressure ionization sources, corona discharge and UV, were tested for possible use in the FAIMS setup. Both sources showed similar ionization efficiency levels. Between the two sources, the UV is a simpler system that requires very low optimization and has very stable ionization rates. Consequently, it was selected as the ionization method for this work. All the required electronics for the ions filtering and detection were also developed. The designed separation voltage circuit, based on the power nMOS inverter configuration, is able to produce rectangular waveforms of up to 1000 Vpp in the MHz range. The compensation voltage (CV) circuit can scan the ion spectra by generating a voltage ramp from -20 to 20 V. The fabricated low current amplifier has a gain of 10^11 with a noise of about 4 fA/Hz^0.5 limited by the thermal noise of the feedback resistor. The experimental parameters can be controlled and monitored by a custom user interface software developed in LabVIEW®. This software also digitalizes, displays and save the measured data. Finally, several measurements were performed to determine the influence of the different experimental parameters in the FAIMS sensitivity and resolution. In order to have a better understanding of the phenomena occurring within the FAIMS, the parameters¿ effects on each of the FAIMS section were studied separately. Also, for the first time, the effects of a synchronous modulation technique (lock-in) in the FAIMS ion current detection were analyzed. Based on the results of these studies, the LoD of the FAIMS system was significantly improved. The extrapolated acetone LoD levels, from the experimental signal amplitude and base line noise, of the developed device are 900ppt and 40ppt at carrier gas flows of 3.05 and 9.5 l/min respectively.

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https://infoscience.epfl.ch/record/220242?ln=fr

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Mario Andres Chavarria Varon
EPFL, 2016
Thèse EPFL

Résumé

Official source

https://infoscience.epfl.ch/record/220242?ln=fr

À propos de ce résultat

Concepts associés (16)

Concepts associés

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Publications associées (13)

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Thiol-targeted microspray mass spectrometry of peptides and proteins through on-line EC-tagging

Loïc Dayon

Modification strategies targeting specific amino acids in proteins are widespread in proteomic analysis. Cysteine residues have received deep consideration in view of their nucleophilic properties and their occurrence in the proteome. A recently developed micro-electrospray emitter for mass spectrometry was used to electrogenerate species reactive towards specific residues in biomolecules. When spraying L-cysteine in the presence of hydroquinone, the thiol cysteine moiety reacts via a 1,4-Michael addition with the benzoquinone electrochemically generated at the electrode. A series of electrogenerated selective electrophiles based on substituted benzoquinones was characterized as tags for L-cysteine. The rate constants pertaining to the addition of L-cysteine onto the benzoquinones were determined through electrochemical techniques. It was shown that the rate constants are primarily dependent on the electronic nature of the substituents. The apparent tagging extents observed for L-cysteine in microspray mass spectrometry experiments were shown to be highly dependent of the ionization efficiencies of the tag. The on-line mass spectrometric electrochemical tagging (EC-tagging) of cysteine residues was studied for peptides. The EC-tagging was tested with the different hydroquinones on an undecapeptide containing one cysteine residue. Methoxycarbonyl-1,4-hydroquinone was shown to be the most efficient probe and revealed to be suitable to count cysteine units in peptides containing up to three cysteines. The number of cysteines corresponds to the number of characteristic mass shifts observed from the unmodified peptide. The identification of bovine serum albumin and human a-lactalbumin digest samples in a peptide mapping strategy were greatly improved by the application of the EC-tagging technique as post-column treatment. Indeed, the determination of cysteine content in the tryptic peptides provides powerful supplementary information to the masses. The tagging method was applied to the determination of four proteins in a model mixture. In parallel, the microspray emitter was characterized as an electrolysis flow cell for the EC-tagging of peptides. The Levich equation was validated as a first approximation for the calculation of the convection-diffusion limiting current in the device. A finite element simulation of the multi-tagging process of peptides was developed to yield the relative distribution and concentration of tags, untagged and tagged species in the microchannel. The main chemical parameters determining the kinetics of the labelling were assessed and discussed considering the microfluidic aspects of the process. The control of the tagging extent allows the simultaneous mass spectrometric analysis of both the unmodified and of the modified peptide(s). This theoretical work has established the range of optimum conditions for the determination of the number of cysteines in peptides containing up to five cysteine groups. The mass spectrometric EC-tagging of cysteine residues in proteins was studied to probe the cysteine environment. An analytical model was developed to calculate rapidly the tagging extent before the spray event. Experiments with unmodified proteins and their chemically reduced forms have highlighted the strong effect of the cysteine site reactivity on the tagging efficiencies. This study has shown relevant parameters for such on-line electrochemical derivatization / mass spectrometric detection strategies. The chemical derivatization of cysteines by benzoquinone reagents was also investigated. These alkylating reagents revealed efficient for diagonal liquid chromatography to isolate cysteinyl peptides by the retention time shifts due to the hydrophobicity of the tags. The work has demonstrated that the inherent electrochemistry of the electrospray can be employed as post column treatment to derivatize cysteinyl biomolecules. Analytical strategies have been developed to take advantage of this electrochemically-controlled modification.

EPFL2006

Chargement

, ,

A force-sensing device to intraoperatively measure knee joint forces and moments to improve the ligament balancing procedure during total knee arthroplasty has been developed. It consists of two sensitive plates, one for each condyle, a tibial base plate and a set of wedges to vary the tibio-femoral gap. Each sensitive plate contains three deformable bridges instrumented with thick-film piezoresistive sensors, which allow the measurement of the amplitude and location of the tibio-femoral contact forces. Their net varus-valgus moment is then computed and regarded as the parameter characterizing the ligamentous balance. An accuracy study demonstrated that the maximum force amplitude and location error are 1.4 N and 0.6 mm respectively, whereas the mean absolute errors are 0.5 N and 0.2 mm. A control experiment with a plastic knee joint model equipped with spring-ligaments attested the device’s suitability for the purpose of ligament balancing. Furthermore, an in-situ trial on a cadaver demonstrated the appropriateness of the measurement scale as well as the consistency between the acquired data and the surgeon’s perception. The obtained results indicate thereby that the developed force-sensing device has a strong potential to offer useful quantitative information and effective assistance during the ligament balancing procedure in total knee arthroplasty.

2005

Chargement

In the past decades, two recording tools have established themselves as the working horses in the field of electrophysiological cell research: the microelectrode array (MEA) and the optical fluorescence imaging. The former is a grid of miniature electrodes allowing to monitor and stimulate cell networks; the latter uses voltage-sensitive dyes (VSDs) rendering the membrane potential visible. So far, researchers trying to combine these two measurement methods face complex electro-optical setups that suffer from the limitations of both techniques. On this ground, it is highly desirable to have a new tool at hand that (a) implements both measurement methods in a single device, (b) offers a high spatio-temporal resolution for both the electrical and the optical sensors, (c) is compact, (d) is easy to handle, and (e) allows long-term measurements. The project, this work is part of, aims to achieve these goals by means of a new concept: the multi-mode sensor array (MMSA). It consists of two parts: (1) a quartz-based microfabricated biointerface housing the sensing devices, i.e. platinum electrodes and amorphous silicon photodiodes; (2) an application specific integrated circuit (ASIC) for the amplification and the conditioning of the detected signals. The two devices are flip-chip bonded together by high-density indium bumps. The resulting measurement tool features a sensor array containing 1024 electrodes and 3072 photodiodes at a pitch of 60 μm and 30 μm, respectively. The main objective of this work is the development of said ASIC with the main task being the design of low-noise, high-density electronic circuits to read the signals detected by the biointerface electrodes and photodiodes. Secondary goals are the packaging of the system and the development of a data acquisition platform to visualise and analyse the measured values. In the course of this dissertation, two ASIC versions were designed: the MMSA I and MMSAII chips. With regard to the electrode low-noise amplifier (LNA), the two versions exhibit substantially different architectures. The MMSAI LNA features a fully-differential architecture, two amplification stages with selectable gain iii Abstract (60/50 dB) and a stable bandwidth of 10 kHz, and two integrated offset compensation techniques. While the measured gain and bandwidth are in good agreement with the simulations, the noise is substantially higher than anticipated since flicker noise was not taken into account in the circuit analysis. Based on the experiences from the MMSA I chip, the second ASIC was developed with a single-ended architecture with a folded-cascode amplifier at its core. It exhibits a gain of 52 dB, a bandwidth of 52 kHz, an average noise of 26 μVrms, and a power consumption of less than 85 μW. The offset compensation allows to deal with input-referred offset in a total range of 40 mV. Furthermore, each pixel was equipped with a sample & hold buffer and a programmable stimulation circuitry. The former stores the amplified signal locally thereby realising an electronic shutter for the electrode signals; the latter is centered around a SRAM (static random access memory) cell and permits the creation of complex stimulation patterns on the array. Comparing the design with literature reveals the competitiveness of the circuit in terms of noise efficiency factor versus area. For the treatment of the photodiode signals, the three-transistor active pixel sensor (APS) architecture is employed due to its simplicity and compactness. To maximise the sensitivity of the sensor, very small transistor dimensions were chosen, thereby minimising the capacitance. The measured responsivity ranges from 0.75 V/μWμs to 0.91 V/μWμs depending on the wavelenght of the incident light. The detectable amplitude can be adjusted by choosing an appropriate integration time. The developed package provides for the biocompatibility of the system, a stable casing, thermal dissipation, a container for the cell culture and nutrient solution, and modularity for easy exchange. The data acquisition platform transfers data at a rate of up to 35 MB/s to a computer via USB 2.0. Furthermore, it offers the creation of protocols to define the course of experiments including the choice of stimulation signal waveform, stimulation patterns, timing information, and recording options.

EPFL2012

Chargement

EPFL2012

Thiol-targeted microspray mass spectrometry of peptides and proteins through on-line EC-tagging

Loïc Dayon

EPFL2006