RT Journal Article
SR Electronic
T1 Fractal circuit sensors enable rapid quantification of biomarkers for donor lung assessment for transplantation
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP e1500417
DO 10.1126/sciadv.1500417
VO 1
IS 7
A1 Sage, Andrew T.
A1 Besant, Justin D.
A1 Mahmoudian, Laili
A1 Poudineh, Mahla
A1 Bai, Xiaohui
A1 Zamel, Ricardo
A1 Hsin, Michael
A1 Sargent, Edward H.
A1 Cypel, Marcelo
A1 Liu, Mingyao
A1 Keshavjee, Shaf
A1 Kelley, Shana O.
YR 2015
UL http://advances.sciencemag.org/content/1/7/e1500417.abstract
AB 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.