MSACL 2025 Abstract

Translating Paper Spray Mass Spectrometry from Clinical R&D to Clinical Patient Care

Taelor M. Zarkovic (1, 2), Jindar N. S. Sboto (1, 2), Jason L. Robinson (3), Jan Palaty (4), Reza Rafizadeh (5, 6), and Chris G. Gill (1, 2, 7)
(1) Centre for Health and Environmental Mass Spectrometry (CHEMS), Chemistry Department, Vancouver Island University, Nanaimo, BC, Canada, (2) Chemistry Department, University of Victoria, Victoria, BC, Canada, (3) Clinical Chemistry Division Head, Health PEI, Charlottetown, PEI, Canada, (4) LifeLabs Medical Laboratories, Burnaby, BC, Canada, (5) BC Mental Health and Substance Use Services, Vancouver, BC, Canada, (6) Department of Psychiatry, University of British Columbia, Vancouver BC, Canada, (7) Department of Occupational and Environmental Health Sciences, University of Washington, Seattle, WA, USA.

Chris Gill, Ph.D. (Presenter) Vancouver Island University

Presenter Bio: Chris is a Chemistry Professor at Vancouver Island University (Nanaimo, BC) as well as Co-Director of the Centre for Health and Environmental Mass Spectrometry (CHEMS). He maintains an active international collaboration network, including the tenure of visiting professorships during sabbaticals in Germany and Italy. He has been awarded the Distinguished Researcher Award at VIU, a Distinguished Chemistry Alumni Award at the University of British Columbia. The CHEMS conducts pure & applied research, with a central theme the development of direct, online mass spectrometry methods for measurements in complex samples. This has lead to numerous advances for direct environmental, industrial and clinical/bioanalytical measurements. The CHEMS development of mobilized direct mass spectrometry platforms for geospatially resolved quantitative environmental measurements as well as numerous hyphenated methodologies has transformed capacity for in field chemical determinations. Chris’ current research interests continue to involve the development of direct mass spectrometry instrumentation and their applications for direct, real-time chemical measurements. This includes high precision systems and approaches for improved environmental monitoring, clinical diagnostics, forensic testing, and the development and implementation of rapid, on-site drug testing strategies for use in the opioid overdose crisis.

Relevant Financial Disclosures (within past 24 months, reported on Apr 16, 2026) No relevant financial relationship(s) to disclose.

INTRODUCTION:
We have been exploring direct mass spectrometry strategies such as paper spray mass spectrometry (PS-MS) as candidate analytical methods to increase throughput in clinical workflows. In PS-MS, direct, measurements in complex samples such as biofluids can be made with small sample aliquots (i.e., ≤ 10 µL) without significant preparation steps. Samples are simply co-deposited on pointed paper strips with internal standards. When the strips are moistened with a suitable solvent, and high voltage applied, ions are generated in a manner akin to electrospray, allowing rapid (ca 1 minute) direct analyte quantitation via tandem mass spectrometry without chromatography. The strips are inexpensive and disposed after each measurement, eliminating carryover. In addition, sample shipping is simplified, since dried on paper biofluid samples do not require refrigeration. PS-MS offers the potential to make rapid, simultaneous measurements of both small and large molecules in a single run.

OBJECTIVES:
This presentation will present several demonstrations of the translation of PS-MS for the rapid, sensitive, and quantitative clinical diagnostics. Several clinical translation projects are currently underway and will be discussed: (1) chronic kidney disease diagnostics utilizing urine samples and non-targeted strategies utilizing machine learning; (2) quantitative therapeutic drug monitoring in serum for antipsychotic drug administration strategy evaluations/compliance, and (3) urinary drug screening for substance use disorder patients.

METHODS:
Paper spray tandem mass spectrometry is implemented with several systems: 1) a commercially available high-throughput paper spray ion source with triple quadrupole mass spectrometers (Thermo Scientific™ TSQ Altis™ and Quantis™ triple quadrupole mass spectrometers with VeriSpray™ sources); 2) HRAM-PS-MS utilizing a third generation, 3D printed PS-MS interface and an Exploris 120™ orbitrap mass spectrometer (Thermo Scientific™). Across all methods, typically 10 µL urine or serum samples are co-deposited with internal standards on PS-MS samples strips using barcode traceable VeriSpray™ PS-MS sample plates (24 strips/plate), allowing unattended measurement of up to 240 samples. Measurements by HRAM-PS-MS were made with the same sample volumes, deposited on individual PS-MS paper strips of the same geometry, but analyzed individually.

RESULTS:
Foundational publications by our group have demonstrated acceptable analytical results for all the translational projects being presented. Our earliest PS-MS publications involved urine drug testing. Work is underway evaluating the translation of PS-MS as a candidate method for urine drug testing in a hospital clinical laboratory in Prince Edward Island.

Published results utilizing both targeted and non-targeted PS-MS to determine ACR ratios and albuminuria classification in urine samples have proven effective. Clinically acceptable LOD/LOQ by PS-MS are possible for quantitative determinations, with a coefficient of determination of R2 = 0.9744 between the PS-MS results and validated clinical methods. Non-targeted HRAM-PS-MS measurements (15 second full scan measurements) in combination with the Random Forest machine learning yields excellent ACR classification accuracy (96.3%), sensitivity (92.5%), specificity (100.0%), with a positive predictive value (100.0%), and negative predictive value (93.0%). These results were achieved with a limited sample sets of anonymous urine samples (56 and 80 respectively). We are currently working with a cohort of over 200 anonymous samples, and are investigating the potential translation of HRAM-PS-MS / AI data analyses to methods employing PS-MS with unit mass resolution (quadrupole) mass spectrometers.

In 2024, we demonstrated that clozapine/norclozapine serum levels determined by PS-MS provides rapid results that compare favorably with those obtained with validated LC-MS methods. We are in the process of establishing a clinical trial to evaluate the effectiveness of utilizing PS-MS in a clinical setting. This prospective, open-label, within individual repeated-measures study will be carried out as part of a collaboration with the BC Psychosis Program (BCPP). The primary objective is to evaluate whether measuring clozapine serum concentration using venous blood sampling with PS-MS is comparable to the standard method using liquid chromatography-mass spectrometry (LC-MS). The secondary objective is to determine whether capillary sampling is equivalent to venous sampling when analyzed with PS-MS.

CONCLUSION:
Paper spray mass spectrometry (PS-MS) provides the direct and rapid measurement of a variety of clinically relevant targets ranging from small molecules to proteins, with results that compare favorably with existing validated methods. The simplified workflows and sample transport possible with PS-MS make it an attractive candidate method for high throughput clinical diagnostics. Several examples illustrating the translation of PS-MS methods to clinical settings are under way and will be discussed.