Label-Free Detection of Tumor Angiogenesis Biomarker Angiopoietin 2 Using Bloch Surface Waves on One Dimensional Photonic Crystals

Abstract

We describe the design and fabrication of biochips based on 1-D photonic crystals supporting Bloch surface waves for label-free optical biosensing. The optical properties of Bloch surface waves are studied in relation to the geometry of the photonic crystals and on the properties of the dielectric materials used for the fabrication. The planar stacks of the biochips are composed of silica, tantala, and titania that were deposited using plasma-ion-assisted evaporation under high-vacuum conditions. The biochip surfaces were functionalized by silanization, and appropriate fluidic cells were designed to operate in an automated platform. An angularly resolved ellipsometric optical sensing apparatus was assembled to carry out the sensing studies. The angular operation is obtained by a focused laser beam at a fixed wavelength and detection of the angular reflectance spectrum by means of an array detector. The results of the experimental characterization of the physical properties of the fabricated biochips show that their characteristics, in terms of sensitivity and figure of merit, match those expected from the numerical simulations. Practical application of the sensor was demonstrated by detecting a specific glycoprotein, Angio-poietin 2, that is involved in angiogenesis and inflammation processes. The protocol used for the label-free detection of Angiopoietin 2 is described, and the results of an exemplary assay, carried out at a relatively high concentration of 1 μg/ml, are given and confirm that an efficient detection can be achieved. The limit of detection of the biochips for Angiopoietin 2, based on the protocol used, is 1.5 pg/mm2 in buffer solution. The efficiency of the label-free assay is confirmed by independent measurements carried out by means of confocal fluorescence microscopy

Towards a Uniform Metrological Assessment of Grating-Based Optical Fiber Sensors: From Refractometers to Biosensors

“…Very recently, Sinibaldi et al [23] pointed out a first preliminary distinction regarding this question, providing also an equation that relates the volume RI sensitivity to the surface sensitivity of the proposed biosensor.…”

Bloch surface wave label-free and fluorescence platform for the detection of VEGF biomarker in biological matrices

“…4 are analyzed according to procedures that are commonly reported in literature (Wang et al, 2009), one can evaluate the limit of detection in the label-free mode as LoD LF = 2 LF / S LF = (11.5 ± 0.5) ng/mL. The LoD LF can be expressed in terms of the minimum mass coverage detectable in the label free mode by making use of the following expression (Sinibaldi et al, 2015b):…”

“…For such a reason, fluorescence schemes exploiting evanescent waves, featuring strong field localization and intensity enhancement at the surface of interest, have been employed (Anopchenko et al, 2016;Cooper, 2002;Descrovi et al, 2013;Fan et al, 2008;Ligler and Taitt, 2008;Zhao et al, 2010). Among evanescent wave sensors, those based on Bloch surface waves (BSW) sustained by dielectric one dimensional photonic crystals (1DPC) (Yeh et al, 1977) have been demonstrated as an effective alternative to SPR for label-free optical biosensing (Konopsky et al, 2013;Rivolo et al, 2012;Rizzo et al, 2014;Shinn and Robertson, 2005;Sinibaldi et al, 2015aSinibaldi et al, , 2015b. The direct comparison of the performance of BSW with SPR biosensors showed that evanescent waves on all-dielectric structures can outperform their metallic analogue (Sinibaldi et al, 2012).…”

Bloch surface wave enhanced biosensor for the direct detection of Angiopoietin-2 tumor biomarker in human plasma

“…Here, we present the detection of both Ang2 spiked in buffer and endogenous Ang2 biomarker directly from human blood plasma, with the sensing platform operating in the fluorescence mode only. While several BSW based biosensors [19,22,[24][25][26][27] were reported for the detection of different analytes, their accuracy was never tested with real clinical samples. Blood plasma, together with serum, is one of the main sources of clinical analytes [28].…”