Development and Study of the Microfluidic Open Interface Coupled with Solid-phase Microextraction for Rapid Analysis
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Date
2022-09-28
Authors
Nazdrajic, Emir
Advisor
Pawliszyn, Janusz
Journal Title
Journal ISSN
Volume Title
Publisher
University of Waterloo
Abstract
Analytical chemistry mainly aims to identify and quantify analytes in matrices of interest. Analytical
chemistry is an indispensable part of chemistry (and other scientific fields) because identification and
quantification rely on repeatable and accurate measurements. Today's gold-standard systems for trace
analysis are mainly chromatographic systems (liquid chromatography or gas chromatography) coupled to
mass spectrometry. These methods attained the gold-standard status because of the overall method
sensitivity and selectivity abilities. However, the main weakness of these systems is that they often require
extensive sample preparation to reach outstanding performance regarding selectivity and sensitivity.
Nevertheless, the chromatography step can be lengthy when selectivity is needed. Mass spectrometry has
improved over the years, encouraging researchers to introduce samples directly to mass spectrometry, thus
circumventing chromatographic separation. This field became known as direct-to-mass spectrometry. One
of the main aims of this field is to avoid lengthy chromatography time and practically have real-time
monitoring or high-throughput/rapid analysis of analytes at trace levels with little or no (laborious) sample
preparation. However, these approaches serve only as the first line of study (rapid screening step), after
which positive samples are submitted for thorough analysis using a gold-standard method. One of the main
disadvantages of direct-to-mass spectrometry analysis is susceptibility to matrix effects (due to lack of
separation), which internal standards can somewhat mitigate. Another disadvantage is instrument
contamination resulting from inadequate or no sample preparation that is sacrificed for the overall rapid
analysis. The most suitable sample preparation for direct-to-mass spectrometry analysis is solid-phase
microextraction. It is a method developed to perform sampling and sample preparation in a single cohesive
step. One of the advantages of this method is the non-exhaustive enrichment. The main advantages of this
sample preparation method include using matrix-compatible coating, which offers analyte enrichment with
minimal or no matrix interference co-enrichment.
Additionally, the open-bed enrichment of solid-phase microextraction offers avenues for high-throughput
sample preparation steps that minimize the overall analytical workflow time. When such analysis is used
for the direct-to-mass spectrometry analysis, the general analytical workflow time is reduced by avoiding
chromatography. Solid-phase microextraction has been coupled directly to mass spectrometry in many
ways. One of the ways solid-phase microextraction can be coupled directly to the mass spectrometry is via
a microfluidic open interface. The microfluidic open interface system coupled to mass spectrometry
comprises a suction component (created by the ionization source of a mass spectrometer), an inflow
component (pumping system), and a desorption chamber. All three components connect to a three-way
chromatographic tee. The main requirement is that the suction component is constant. The liquid level in
the desorption chamber can be introduced to the mass spectrometer by changing the inflow. Solid-phase
microextraction devices (after the enrichment step) are then introduced to the very low-volume desorption
chamber for analysis. The inflow stops after a short desorption time (e.g., 5 s). The suction component
aspirates the volume of the desorption chamber, thus injecting the solution into the mass spectrometer for
the analysis. The main highlights of the microfluidic open interface coupled to a mass spectrometer are
desorption in a flow-isolated system and desorption into a low volume, which provides a tall Gaussian peak.
The overall objective of this thesis is to redesign the microfluidic open interface system to demonstrate
automation of the analysis workflow and make it suitable for rapid analysis.
Firstly, Chapter 2 identifies the disadvantages of the existing microfluidic open interface system, which
are used to improve the next design. The new system contains commonly available material to make the
system approachable. Additionally, all system components are automated (by writing a homemade program
from scratch), reducing the error from the manual operation. Nevertheless, this chapter depicts how the
solid-phase microextraction coating design is essential for optimal desorption and analysis sensitivity.
Chapter 3 expands on the fundamental idea raised towards the end of Chapter 2 by quantifying the mass
transfer resistance in separation media. The effect of sorbent in matrix-compatible binders is crucial to
understand for some applications. The extraction (or the desorption) of analytes will be controlled by the effective diffusion coefficient in the coating rather than at the interface or boundary layer, as it was a most
common assumption before. The following two chapters, Chapter 4 and Chapter 5, contain applications
that utilize the two designs of the microfluidic open interface for the analysis of immunosuppressive drugs
and fentanyl analytes from the whole blood, respectively. For both works, the sample preparation is done
in a high-throughput fashion. After the analysis with a microfluidic open interface, the overall method times
(per sample) are substantially lower than gold-standard methods reported in the literature while maintaining
similar detection and quantification limits compared to state-of-the-art reported methods. Therefore, solidphase microextraction coupled directly to mass spectrometry via a microfluidic open interface offers a
suitable replacement for a gold-standard method. Chapter 6 contains an alternative and simplified use of
the microfluidic open interface coupled to the homemade ultraviolet-visible light detection system. Finally,
Chapter 7 encompasses the main findings and offers a future perspective on using solid-phase
microextraction with a microfluidic open interface coupled directly to mass spectrometry or an alternative
detector, such as ultraviolet-visible light detection.
Description
Keywords
microfluidic open interface (MOI), solid-phase microextraction (SPME), direct-to-mass spectrometry