Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors

Abstract

We experimentally demonstrate label-free photonic crystal (PC) microcavity biosensors in silicon-on-insulator (SOI) to detect the epithelial-mesenchymal transition (EMT) transcription factor, ZEB1, in minute volumes of sample. Multiplexed specific detection of ZEB1 in lysates from NCI-H358 lung cancer cells down to an estimated concentration of 2 cells per micro-liter is demonstrated. L13 photonic crystal microcavities, coupled to W1 photonic crystal waveguides, are employed in which resonances show high Q in the bio-ambient phosphate buffered saline (PBS). When the sensor surface is derivatized with a specific antibody, the binding of the corresponding antigen from a complex whole-cell lysate generates a change in refractive index in the vicinity of the photonic crystal microcavity, leading to a change in the resonance wavelength of the resonance modes of the photonic crystal microcavity. The shift in the resonance wavelength reveals the presence of the antigen. The sensor cavity has a surface area of ~11 μm2. Multiplexed sensors permit simultaneous detection of many binding interactions with specific immobilized antibodies from the same bio-sample at the same instant of time. Specificity was demonstrated using a sandwich assay which further amplifies the detection sensitivity at low concentrations. The device represents a proof-of-concept demonstration of label-free, high throughput, multiplexed detection of cancer cells with specificity and sensitivity on a silicon chip platform.

Advances in optoplasmonic sensors – combining optical nano/microcavities and photonic crystals with plasmonic nanostructures and nanoparticles

“…albumin (BSA) proteins [136][137][138][139][140][141][142][143], single-stranded DNA [144], optically trapped bacteria [145,146], NCI-H358 lung cancer cell line lysates [147], and human papillomavirus virus-like particles [148][149][150]. Sophisticated slotted waveguides [141,[151][152][153] as well as nanobeam cavities [140,146,150,[154][155][156][157][158][159][160] have also been implemented for analyte-specific stoichiometric studies and biomolecule micromanipulation.…”

Silicon on-chip bandpass filters for the multiplexing of high sensitivity photonic crystal microcavity biosensors

“…Photonic crystal (PC) microcavities side-coupled to photonic crystal waveguides (PCWs) have been demonstrated as a competitive candidate for high-sensitivity biosensors. [1][2][3][4][5][6][7][8] The ability of PC microcavities to confine light to ultra-small mode volumes promises the potential for high-density microarrays with slow light enhanced sensitivity to refractive index changes of the ambient. Biosensor microarrays have been demonstrated with multiplexed PC microcavities for the specific detection of lung cancer cell line lysates, 3 allowing the specific detection of different biomolecules on the same chip.…”

“…For the abovementioned biosensor microarrays, 3 multiple optical fibers or a fiber array at the output is necessary in order to monitor the binding reactions from all PC microcavities simultaneously. However, from the application perspective, when designing a portable device, with limited space for off-chip optical components, one needs to maximize the number of sensors that can be simultaneously interrogated with a single input and output, making the packaging and alignment robust and cost-effective.…”

Direct Detection of Transcription Factors in Cotyledons during Seedling Development Using Sensitive Silicon-Substrate Photonic Crystal Protein Arrays

“…One recent report illustrates use of the microcavity biosensors to detect a lung cancer antigen in lysates of a recombinant lung cancer cell line, in which expression of the antigen is induced (Chakravarty et al, 2013). However, neither PCEF arrays nor PC biosensors have been tested for performance to detect proteins in plant systems.…”

“…Other types of PC structures that do not use fluorescence include biosensors, in which detection is performed by measuring shifts in the PC resonant wavelength for various analytes that bind to the surface (Pal et al, 2011;Scullion et al, 2011;Chakravarty et al, 2013;Zou et al, 2014). One recent report illustrates use of the microcavity biosensors to detect a lung cancer antigen in lysates of a recombinant lung cancer cell line, in which expression of the antigen is induced (Chakravarty et al, 2013).…”