Development of a Microfluidic Open Interface with Flow Isolated Desorption Volume for the Direct Coupling of SPME Devices to Mass Spectrometry

Abstract

Technologies that efficiently integrate the sampling and sample preparation steps with direct introduction to mass spectrometry (MS), providing simple and sensitive analytical workflows as well as capabilities for automation, can generate a great impact in a vast variety of fields, such as in clinical, environmental, and food-science applications. In this study, a novel approach that facilitates direct coupling of Bio-SPME devices to MS using a microfluidic design is presented. This technology, named microfluidic open interface (MOI), which operates under the concept of flow-isolated desorption volume, consists of an open-to-ambient desorption chamber (V ≤ 7 μL) connected to an ionization source. Subsequently, compounds of interest are transported to the ionization source by means of the self-aspiration process intrinsic of these interfaces. Thus, any ionization technology that provides a reliable and constant suction, such as electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), or inductively coupled plasma ionization (ICP), can be hyphenated to MOI. Using this setup, the desorption chamber is used to release target compounds from the coating, while the isolation of the flow enables the ionization source to be continuously fed with solvent, all without the necessity of employment of additional valves. As a proof of concept, the design was applied to an ESI-MS/MS system for experimental validation. Furthermore, numerical simulations were undertaken to provide a detailed understanding of the fluid flow pattern inside the interface, then used to optimize the system for better efficiency. The analytical workflow of the developed Bio-SPME-MOI-MS setup consists of the direct immersion of SPME fibers into the matrix to extract/enrich analytes of interest within a short period of time, followed by a rinsing step with water to remove potentially adhering proteins, salts, and/or other interfering compounds. Next, the fiber is inserted into the MOI for desorption of compounds of interest. Finally, the volume contained in the chamber is drained and moved toward the electrospray needle for ionization and direct introduction to MS. Aiming to validate the technology, the fast determination of selected immunosuppressive drugs (e.g., tacrolimus, cyclosporine, sirolimus, and everolimus) from 100 μL of whole blood was assessed. Limits of quantitation in the subppb range were obtained for all studied compounds. Good linearity (r ≥ 0.99) and excellent precision, with (8%) and without (14%) internal standard correction, were attained.

Fast screening of illicit drugs in beverages and biological fluids by direct coupling of thin film microextraction to dielectric barrier discharge ionization-mass spectrometry

“…30 Tascon et al quantified immunosuppressants in whole blood at the sub-ppb level with a microfluidic open interface (MOI) ionization source. 31 Coated blade spray 32 (CBS) was also used for the quantification od drugs of abuse in human urine and plasma. These techniques, namely OPP, MOI, and CBS, represent a viable alternative to DBDI when an ESI-like ionization is preferred.…”

High‐throughput quantification of drugs of abuse in biofluids via 96‐solid‐phase microextraction–transmission mode and direct analysis in real time mass spectrometry

“…This includes extraction and desorption time. This is comparable to other SPME‐AIMS technologies like coated blade spray (CBS) (29 s) and open port probe (15–20 s). In paper spray, drying time (minutes, in some cases hours) and spraying times (seconds to minutes) tend to vary with applications, but total analysis times usually are not excessively long.…”

“…SPME is renowned for its structural flexibility, as its format can be re-shaped in order to comply with the requirements of varying direct-to-MS approaches. [23][24][25][26][27][28] SPME uses an open-bed format 29 that works by directly exposing the sampling device, which consists of an extractive phase (coating) that has been immobilized onto a selected substrate, to a matrix of interest. SPME sampling only extracts a fraction of analyte, and the use of biocompatible protective coatings, such as polyacrylonitrile (PAN), helps to prevent the adherence of unwanted biologicals (reducing clogging issues and artifact formations), thus enabling a "cleaner" introduction of the sample into the mass spectrometer.…”

Hunting Molecules in Complex Matrices with SPME Arrows: A Review

“…Other options include but are not limited to direct analysis in real time (DART) [63][64][65], atmospheric pressure photon ionization (APPI) [66], and thermal desorption-electrospray ionization (TD-ESI) [67]. It is anticipated that SPME Arrow-like geometries [11] compatible with liquid desorption and complex biological matrices will be developed in the near future and potentially coupled to direct-to-MS technologies such nano-electrospray ionization (nano-ESI) [68], desorption electrospray ionization [69], and the microfluidic open interface (also known as Open Probe Sampling Interface, OPSI) [70][71][72], as means to enhance the speed of analysis and the sensitivity [73]. Areas where such devices can make a great impact include but are not limited to, food fraud [74], volatomics [64], and rapid screening in the clinical chemistry realm [75].…”