In situ, dual-mode monitoring of organ-on-a-chip with smartphone-based fluorescence microscope

• Published in: Biosensors & bioelectronics Vol. 86; pp. 697 - 705
• Main Authors: Cho, Soohee, Islas-Robles, Argel, Nicolini, Ariana M., Monks, Terrence J., Yoon, Jeong-Yeol
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.12.2016
• Subjects: 786-O cells; Agglutination Tests - instrumentation; Assaying; Bioprosthesis; Biosensors; Brushes; Cell Line; Devices; Equipment Design; Equipment Failure Analysis; Fluorescence; Humans; Immunoassay - instrumentation; Immunoassay - methods; Kidney - drug effects; Kidney - immunology; Kidney-on-a-chip; Kidneys, Artificial; Lab-On-A-Chip Devices; Microscopes; Microscopy, Fluorescence - instrumentation; Microscopy, Fluorescence - methods; Mobile Applications; Monitoring; Nanostructure; Organ Culture Techniques - instrumentation; Organ Culture Techniques - methods; Particle immunoagglutination; Reproducibility of Results; Sensitivity and Specificity; Smartphone; Smartphone microscope; Toxicity Tests - instrumentation; Toxicity Tests - methods; User-Computer Interface; γ-glutamyl transpeptidase; 786-O cells; Kidney-on-a-chip; γ-glutamyl transpeptidase; Particle immunoagglutination; Smartphone microscope
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2016.07.015

The use of organ-on-a-chip (OOC) platforms enables improved simulation of the human kidney's response to nephrotoxic drugs. The standard method of analyzing nephrotoxicity from existing OOC has majorly consisted of invasively collecting samples (cells, lysates, media, etc.) from an OOC. Such disruptive analyses potentiate contamination, disrupt the replicated in vivo environment, and require expertize to execute. Moreover, traditional analyses, including immunofluorescence microscopy, immunoblot, and microplate immunoassay are essentially not in situ and require substantial time, resources, and costs. In the present work, the incorporation of fluorescence nanoparticle immunocapture/immunoagglutination assay into an OOC enabled dual-mode monitoring of drug-induced nephrotoxicity in situ. A smartphone-based fluorescence microscope was fabricated as a handheld in situ monitoring device attached to an OOC. Both the presence of γ-glutamyl transpeptidase (GGT) on the apical brush-border membrane of 786-O proximal tubule cells within the OOC surface, and the release of GGT to the outflow of the OOC were evaluated with the fluorescence scatter detection of captured and immunoagglutinated anti-GGT conjugated nanoparticles. This dual-mode assay method provides a novel groundbreaking tool to enable the internal and external in situ monitoring of the OOC, which may be integrated into any existing OOCs to facilitate their subsequent analyses. •Non-destructive, in situ monitoring of drug-induced nephrotoxicity on kidney-on-a-chip.•Dual mode monitoring of both inside and outside the organ-on-a-chip.•Immunocapture and immunoagglutination monitor both on-chip expression and outflow shedding.•Smartphone-based fluorescence microscope quantifies immunocapture and immunoagglutination.