br Keywords br Black phosphorus
Label-free Neuron-specific enolase
We propose the first black phosphorus (BP) – fiber optic biosensor for ultrasensitive diagnosis of human neuron-specific enolase (NSE) cancer biomarkers. A novel optical-nano configuration has been exploited by integrating BP nanosheets with a largely tilted fiber grating (BP-TFG), where the BP is bio-functionalized by the poly-L-lysine acting as a critical cross-linker to facilitate bio-nano-photonic interface with extremely enhanced light-matter interaction. BP nanosheets are synthesized by a liquid ultrasonication-based exfoliation and deposited on fiber device by an in-situ layer-by-layer method. The BP-induced optical modulation eﬀects in terms of thickness-tunable feature, polarization-dependence and enhanced light-matter interaction are experimentally investigated. The anti-NSE immobilized BP-TFG biosensor has been implemented to detect NSE biomarkers demonstrating ultrahigh sensitivity with limit of detection down to 1.0 pg/mL, which is 4 orders magnitude lower than NSE cut-oﬀ value of small cell lung cancer. The enhanced sensitivity of BP-TFG is 100-fold higher than graphene oxide or AuNPs based biosensors. We believe that BP-fiber optic configuration opens a new bio-nano-photonic platform for the applications in healthcare, biomedical, food safety and environmental monitoring.
2D-layered materials have attracted enormous attention due to their extraordinary mechanical, electronic, optical and chemical properties (Novoselov et al., 2004; Geim, 2009; Huang et al., 2013). Various na-nomaterials including graphene, transition metal dichalcogenides (TMDs) and boron/carbon nitride have been developed for widespread applications in electronics, optical modulators, 340774-69-8 storages and sensors (Sun et al., 2016; Bonaccorse et al., 2010; Loh et al., 2010). However, the intrinsic shortcomings such as the lack of bandgap in graphene and the lower carrier mobility in molybdenum disulfide limit their utilities. As a new member of 2D materials family, 2D-layered black phosphorus (BP) has triggered renaissance of research interest since its first mechanical exfoliation from bulk BP in 2014 (Reich, 2014; Li et al., 2014; Xia et al., 2014; Liu et al., 2014). BP has a puckered lattice configuration along the armchair direction and a bilayer struc-ture along the zigzag direction. BP consists of corrugated planes of phosphorus atoms with strong in-plane covalent bonding and weak interlayer van der Waals interactions. Due to the unique puckered
∗ Corresponding author. E-mail address: [email protected] (X. Chen).
orthorhombic structure and in-plane anisotropy, BP possesses much higher surface-to-volume ratio, extremely large hole mobility, and su-perior molecular adsorption energy which surpass those of other 2D materials (Reich, 2014; Li et al., 2014). As a new class of 2D materials, BP has a layer-dependent bandgap ranging from ∼0.3 eV for bulk to ∼2.0 eV for monolayer (Liu et al., 2014), which can bridge the gap between the gapless graphene and large bandgap TMDs (Kim et al., 2015; Rodin et al., 2014). Although numerous investigations have been conducted to study the optoelectronic properties and applications of BP, little attention has been paid to its potential biomedical applications. This might be mainly due to the lack of biocompatibility of BP hence low biological activities upon exposure to biological environment with small biomolecules and low concentrations (Li et al., 2015; Abbas et al., 2015; Sun et al., 2015; Hanlon et al., 2016; Kumar et al., 2016; Shao et al., 2016).
Neuron-specific enolase (NSE) is a highly specific cancer biomarker that has been detected in patients with certain tumors, such as neu-roendocrine tumor, lung cancer, medullary thyroid cancer, carcinoid tumors, endocrine tumors of the pancreas, and melanoma (Isgro et al.,
2015). Usually, the concentration of the biomarker secreted to the blood stream by tumors in their early stages of growth is very low, therefore it remains a challenge to develop a sensitive method to detect the biomarkers. Determination of NSE levels in clinical practice can provide information about tumor burden, number of metastatic sites and response to the treatment. Small cell lung cancer (SCLC) has been noted for high malignance, short doubling time, early metastasis, easy recurrence and high mortality (Van Meerbeeck et al., 2011). NSE is currently the most reliable tumor biomarker in diagnosis, prognosis and follow-up of SCLC (Isgro et al., 2015; Van Meerbeeck et al., 2011). NSE is used to provide quantitative measures to identify SCLC, with the cut-oﬀ value of 15.2 ng/mL in clinical diagnosis (Wang et al., 2013).