Development of highly reliable SERS‐active photonic crystal fiber probe and its application in the detection of ovarian cancer biomarker in cyst fluid

Abstract

Conventionally Surface‐enhanced Raman spectroscopy (SERS) is realized by adsorbing analytes onto nano‐roughened planar substrate coated with noble metals (silver or gold) or their colloidal nanoparticles (NPs). Nanoscale irregularities in such substrates/NPs could lead to SERS sensors with poor reproducibility and repeatability. Herein, we demonstrate a suspended core photonic crystal fiber (PCF) based SERS sensor with extremely high reproducibility and repeatability in measurement with a relative SD of only 1.5% and 4.6%, respectively, which makes it more reliable than any existing SERS sensor platforms. In addition, our platform could improve the detection sensitivity owing to the increased interaction area between the guided light and the analyte, which is incorporated into the holes that runs along the length of the PCF. Numerical calculation established the significance of the interplay between light coupling efficiency and evanescent field distribution, which could eventually determine the sensitivity and reliability of the developed SERS active‐PCF sensor. As a proof of concept, using this sensor, we demonstrated the detection of haptoglobin, a biomarker for ovarian cancer, contained within the ovarian cyst fluid, which facilitated in differentiating the stages of cancer. We envision that with necessary refinements, this platform could potentially be translated as a next‐generation highly sensitive SERS‐active opto‐fluidic biopsy needle for the detection of biomarkers in body fluids.

Optical Fiber Optofluidic Bio‐Chemical Sensors: A Review

“…the core were modified by Ag NPs through self-assembly, which ensured that a large number of hot spots could increase the SERS enhancement effect and a high enhancement factor of 1.3 × 10 9 . Experimental results confirmed that the sensor could detect ceftriaxone in real-time with a low detection limit of 10 -6 M. Recently, by modifying fluid channels around the core of SCF with Au NPs in self-assembly manner, Beffara's research group designed and fabricated an excellent in-fiber SERS sensing platform with superior reproducibility and repeatability of 1.5% and 4.6%, [332] as shown in Figure 49. The structural advantages of SCF ensured large active area and enhanced SERS signal.…”

“…First, the receptor molecules with strong Raman activity are used to modify the antibody to achieve the detection of biomarkers. [332] Second, we can modify the SERS substrate with some probe molecules with strong Raman activity such as GOD and malachite green isothiocyanate (MGITC). Then, according to the change of the SERS spectrum caused by the quantitative binding between these probe molecules and the target analytes, highly sensitive detection of weak Raman active molecular can be achieved.…”

Optimization and performance analysis of SERS-active suspended core photonic crystal fibers

“…Previously we have found that for the anchored configuration, 1X concentration of 60 nm Au NPs provides optimum SERS enhancement [34]. In the current study, we anchored the Au NPs inside the SuC-PCFs with 0.9 µm, 1.4 µm and 3.5 µm core and we compared their SERS response to the best concentration of Au NPs in injected configuration, respectively.…”

“…The different solutions were prepared so that the concentration of ATP was constant among all samples, ie 1 mM. In our previous study [34], we easily detected nM concentrations of ATP and we demonstrated the linearity response of the SuC-PCFs for concentration range from 1 µM to 1 mM. Here, we used 1 mM ATP because we wanted to easily detect the SERS intensity even with very low concentration of Au NPs.…”

“…Furthermore, the core size also plays a significant role in the coupling efficiency between the PCF-probe and the Raman spectrometer. In a previous study, we demonstrated the necessity of using a PCF with an optimized core size, not the smallest, to achieve efficient couplings and to limit the effect of operator misalignments on the measurement reliability [34].…”