Development of a microdialysis probe with embedded sample storage for biomarker recovery

Abstract

Subfertility and recurrent miscarriage are present within 6% and 2% of the female population respectively1. These pathologies can bring psychological harm to individuals and families2, however the biological mechanisms that underpin these issues are not fully understood, with up to 50% of the cases lacking an etiology3 Understanding the biochemical environment inside the uterus allows clinicians greater insight into pathologies arising from dysregulation at a cellular level. Current techniques for monitoring these biochemical changes focus on point measurements, such as phlebotomy or invasive draining procedures, which can lack the information that can be garnered by measuring the changes over the course of minutes or hours. Microdialysis has proven to be a technique that can monitor changes with high spatial resolution by bringing a semipermeable membrane in to close contact with the area of interest. Despite its success within the measurement of rapidly changing biomarkers, such as neurotransmitters, the application of microdialysis to long term monitoring is hampered by technical limitations brought about by the inability to preserve temporal resolution whilst allowing patients relative ease of movement.
Here, a microdialysis probe with embedded sample storage is developed to overcome these limitations. The use of microfluidics, specifically that of plug flow and capillary droplet traps, allowed for16nL samples to be stored within the body of the probe in addressable arrays, paving the way for further analysis. The integration of semipermeable membranes to the body of these microfabricated probes resulted in novel bonding techniques that allowed for the bonding of Polyethersulfone, a thermally stable and solvent resistant, semipermeable membrane to SU-8, a common epoxy-based photoresist. The resulting microdialysis probes were validated against commercially available probes and showed viability in recovering biomarkers. Finally, a proof-of-concept experiment was undertaken that demonstrated the possibility of carrying out assays on the chip.

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Identifiers

ORCID for Joshua Robertson: orcid.org/0000-0003-3952-754X

ORCID for Hywel Morgan: orcid.org/0000-0003-4850-5676

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