Erlotinib and gefitinib tyrosine kinase inhibitors (TKIs) were serendipitously found to be the most effective in advanced NSCLC clinical development. They are reversible small-molecule ATP analogues originally designed to inhibit the TK activity of wild-type EGFR. However, patients ultimately develop disease progression, often driven by the acquisition of a second T790M EGFR TKI resistance mutation. AZD9291 is a novel oral, potent, and selective third-generation irreversible inhibitor of both EGFR-mutant sensitizing and T790M resistance mutants that spares wild-type EGFR. Unfortunately, although patients with EGFR-mutant tumours typically show a good initial response to TKIs, most tumour-tissue patients have a number of mechanisms that mediate EGFR TKI resistance  after approximately 9 to 14 months of continuous treatment. Furthermore, these TKIs are associated with side effects that include skin rash and diarrhoea that are due to inhibition of wild-type EGFR in skin and gastrointestinal organs. In the clinic, the keys of factors of chemotherapy failure are resistance and side effects. As a monotherapy, they have failed to overcome EGFR-mutant mediated resistance in patients, and it is difficult to control the quantity of drugs for inhibition of wild-type EGFR or cell injury in cancer therapy.

Facing the above challenges, it is essential to get as much of the optical power as possible to propagate in the sensing region. Investigation of the mode power distribution suggests us to design a configuration that contains the sample in the guiding layer of the waveguide, where oscillating wave is located and most of the mode power concentrates. Addressed this issue, a hollow-core metal-cladding optofluidic resonator is developed to carry out the experiment. In this design the use of double metal claddings which exhibit negative dielectric constant implies that the effective index of the guided modes can exist in the region of 0 < N < 1, which is usually prohibited for the conventional guided modes and the surface plasmon resonance. Excitation of the ultrahigh order modes (UOMs) with N→0 which means group velocity approaches zero maximizes the interaction between tumor cells and the drugs. Furthermore, owing to light power concentrated in the guiding region it give rise to an enlargement of the luminescent efficiency. These two measures make it possible to enhance the sensitivity of the platform. Experiment results have proved that optofluidic resonators provide an effective way to detect drug interactions in real time using EGFR and cancer cells process with CCD real-time monitoring of ATR shifts.

Publication: Hailang Dai, Yihang Jiao, Zhangchi Sun, Zhuangqi Cao and Xianfeng Chen, Label-free real-time ultrasensitive monitoring of non-small cell lung cancer cell interaction with drugs, 9(9), 4149-4161(2018).