The analysis of cell signaling activities such as cytokine secretion provides invaluable insights for understanding the currently incurable diseases and developing novel cell therapies. Unraveling the dynamic signaling profiles requires the implementation of a real-time monitoring methodology for precise analysis.
In BIOS, we have developed a powerful nanoplasmonic biosensor based on gold plasmonic nanohole arrays for label-free biodetection (Figure 1). The gold nanohole arrays facilitate the so-called unique optical phenomenon, extraordinary optical transmission (EOT), which enables ultra-sensitive and high-throughput biomolecular detection.
Figure 1. Detection principle of nanohole array-based plasmonic biosensor
The biosensor can be integrated with the state-of-the-art microfluidics system that provides well-controlled liquid handling and live cell culture conditions for long-term monitoring (Figure 2). We have also demonstrated the application of this biosensor for multiplexed bacteria detection, drug effect evaluation and protein secretome analysis from live cells. This innovative biosensor system is anticipated to be a powerful tool to probe live cell signaling at multiple levels for basic and clinical research, disease diagnostics and novel therapy development.
Figure 2. Application of the integrated label-free biosensor for various biochemical analyses.
 X. Li, M. Soler, C. I. Özdemir, A. Belushkin, F. Yesilköy, and H. Altug, “Plasmonic nanohole array biosensor for label-free and real-time analysis of live cell secretion,” Lab Chip, vol. 17, no. 13, pp. 2208–2217, Jun. 2017.
 M. Soler, A. Belushkin, A. Cavallini, C. Kebbi-Beghdadi, G. Greub, and H. Altug, “Multiplexed nanoplasmonic biosensor for one-step simultaneous detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine,” Biosensors and Bioelectronics, vol. 94, no. Supplement C, pp. 560–567, Aug. 2017.
 T. Kilic, M. Soler, N. Fahimi-Kashani, H. Altug, and S. Carrara, “Mining the Potential of Label-Free Biosensors for In Vitro Antipsychotic Drug Screening,” Biosensors, vol. 8, no. 1, p. 6, Mar. 2018.
 X. Li et al., “Label-Free Optofluidic Nanobiosensor Enables Real-Time Analysis of Single-Cell Cytokine Secretion,” Small, vol. 14, no. 26, p. 1800698, Jun. 2018.
 M. Soler, X. Li, A. John-Herpin, J. Schmidt, G. Coukos, and H. Altug, “Two-Dimensional Label-Free Affinity Analysis of Tumor-Specific CD8 T Cells with a Biomimetic Plasmonic Sensor,” ACS Sens., vol. 3, no. 11, pp. 2286–2295, Nov. 2018.