title: Low invasive in vivo tissue sampling for monitoring biomarkers and drugs during surgery.
abstract: The techniques currently used for drug, metabolite, and biomarker determination are based on sample collection, and therefore they are not suitable for repeated analysis because of the high invasiveness. Here, we present a novel method of biochemical analysis directly in organ during operation without need of a separate sample collection step: solid-phase microextraction (SPME). The approach is based on flexible microprobe coated with biocompatible extraction phase that is inserted to the tissue with no damage or disturbance of the organ. The method was evaluated during lung and liver transplantations using normothermic ex vivo liver perfusion (NEVLP) and ex vivo lung perfusion (EVLP). The study demonstrated feasibility of the method to extract wide range of endogenous compounds and drugs. Statistical analysis allowed observing metabolic changes of lung during cold ischemic time, perfusion, and reperfusion. It was also demonstrated that the level of drugs and their metabolites can be monitored over time. Based on the methylprednisolone as a selected example, the impairment of enzymatic properties of liver was detected in the injured organs but not in healthy control. This finding was supported by changes in pathways of endogenous metabolites. The SPME probe was also used for analysis of perfusion fluid using stopcock connection. The evaluation of biochemical profile of perfusates demonstrated potential of the approach for monitoring organ function during ex vivo perfusion. The simplicity of the device makes it convenient to use by medical personnel. With the microprobe, different areas of the organ or various organs can be sampled simultaneously. The technology allows assessment of organ function by biochemical profiling, determination of potential biomarkers, and drug monitoring. The use of this method for preintervention analysis could enhance the decision-making process for the best possible personalized approach, whereas post-transplantation monitoring would be used for graft assessments and fast response in case of organ failure.
authors.affiliation: Department of Chemistry, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bojko
authors.affiliation: Department of Chemistry, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Gorynski
authors.affiliation: Department of Chemistry, University of Waterloo, Waterloo, ON, Canada.
authors.forename: German A
authors.initials: GA
authors.lastname: Gomez-Rios
authors.affiliation: Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Knaak
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network and Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Tiago
authors.initials: T
authors.lastname: Machuca
authors.affiliation: Department of Chemistry, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Erasmus
authors.initials: E
authors.lastname: Cudjoe
authors.affiliation: Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
authors.forename: Vinzent N
authors.initials: VN
authors.lastname: Spetzler
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network and Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsin
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network and Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cypel
authors.affiliation: Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Selzner
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network and Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network and Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshjavee
authors.affiliation: Department of Chemistry, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Janusz
authors.initials: J
authors.lastname: Pawliszyn
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D007432:Intraoperative Period; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000378:metabolism; D052617:Solid Phase Microextraction; D013552:Swine
chemical_list: D015415:Biomarkers; D004364:Pharmaceutical Preparations