title: Fractal circuit sensors enable rapid quantification of biomarkers for donor lung assessment for transplantation.
abstract: Biomarker profiling is being rapidly incorporated in many areas of modern medical practice to improve the precision of clinical decision-making. This potential improvement, however, has not been transferred to the practice of organ assessment and transplantation because previously developed gene-profiling techniques require an extended period of time to perform, making them unsuitable in the time-sensitive organ assessment process. We sought to develop a novel class of chip-based sensors that would enable rapid analysis of tissue levels of preimplantation mRNA markers that correlate with the development of primary graft dysfunction (PGD) in recipients after transplant. Using fractal circuit sensors (FraCS), three-dimensional metal structures with large surface areas, we were able to rapidly (<20 min) and reproducibly quantify small differences in the expression of interleukin-6 (IL-6), IL-10, and ATP11B mRNA in donor lung biopsies. A proof-of-concept study using 52 human donor lungs was performed to develop a model that was used to predict, with excellent sensitivity (74%) and specificity (91%), the incidence of PGD for a donor lung. Thus, the FraCS-based approach delivers a key predictive value test that could be applied to enhance transplant patient outcomes. This work provides an important step toward bringing rapid diagnostic mRNA profiling to clinical application in lung transplantation.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Sage
authors.affiliation: Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Besant
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
authors.forename: Laili
authors.initials: L
authors.lastname: Mahmoudian
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada.
authors.forename: Mahla
authors.initials: M
authors.lastname: Poudineh
authors.affiliation: Division of Thoracic Surgery, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.affiliation: Division of Thoracic Surgery, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Zamel
authors.affiliation: Division of Thoracic Surgery, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsin
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Sargent
authors.affiliation: Division of Thoracic Surgery, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cypel
authors.affiliation: Division of Thoracic Surgery, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Division of Thoracic Surgery, University of Toronto, Toronto, Ontario M5G 1L7, Canada. ; Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. ; Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada. ; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
authors.forename: Shana O
authors.initials: SO
authors.lastname: Kelley
keywords: Electrochemical sensors; Molecular analysis; Organ transplantation; mRNA profiling