Elsevier

Biosensors and Bioelectronics

Volume 121, 15 December 2018, Pages 243-249
Biosensors and Bioelectronics

Biofunctionalized two-dimensional Ti3C2 MXenes for ultrasensitive detection of cancer biomarker

https://doi.org/10.1016/j.bios.2018.08.076Get rights and content

Highlights

  • Two-dimensional Ti3C2-MXene nanosheets were synthesized by the MILD method.

  • Single/few layered MXene nanosheets were functionalized via APTES (f-Ti3C2-MXene).

  • The electrochemical behavior of f-Ti3C2-MXene was explored.

  • f-Ti3C2-MXene was biofunctionalized for electrochemical detection of CEA.

  • It exhibits a wide linear detection range of 0.0001–2000 ng mL−1.

Abstract

In this work, ultrathin Ti3C2-MXene nanosheets were synthesized by minimally intensive layer delamination methods, and uniformly functionalized with aminosilane (f-Ti3C2-MXene) to provide a covalent binding for the immobilized bio-receptor (anti-CEA) for label free, ultrasensitive detection of cancer biomarker (carcinoembryonic antigen, CEA). The effect of different redox probes on the electrochemical behavior of f-Ti3C2-MXene was investigated and found that hexaammineruthenium ([Ru(NH3)6]3+) is the preferable redox probe for biosensing. The fabricated biofunctionalized Ti3C2-MXene exhibits a linear detection range of 0.0001–2000 ng mL−1 with sensitivity of 37.9 µA ng−1 mL cm−2 per decade. The wider linear detection range of our f-Ti3C2-MXene is not only higher than previously reported pristine 2D nanomaterials, but is even comparable to other hybrid 2D nanomaterials. We believe that this work opens a new window for development of MXene-based highly sensitive DNA, aptamer, enzyme, antibody, and cell based biosensors, and could be further used in drug delivery application.

Introduction

Ultrathin two-dimensional (2D) nanomaterials possess distinctive set of properties including large surface area and anisotropic electron transport behavior which make them highly promising transducer materials for applications in biosensing (Ji et al., 2017, Kalantar-zadeh and Ou, 2015, Tan et al., 2017, Wen et al., 2017). However, these 2D materials usually have drawbacks that limit their performance in biosensors, such as low electrical conductivity (graphitic carbon nitride, MoS2), hydrophobicity (MoS2, graphene), and very stable surfaces that limits incorporation of functional groups to enable transducer surfaces. For example, in the case of graphene, functionalization can only be done in surface defects and edges and MoS2 is even more difficult to functionalize. Recently, a new group of 2D nanomaterials have emerged that hold the potential to overcome these problems. These materials, known as MXenes, belong to a group of 2D transition metal carbides/carbonitrides that are typically obtained by selective etching of the A-layers from Mn+1AXn (MAX) phases (where M is an early transition metal, A is usually group of 13 and 14 element and X is carbon or a combination of C and nitrogen and n = 1–3). Etching the A-layers results in surface terminations with functional groups such as OH-, O2- and F−1 (Naguib et al., 2011, Naguib et al., 2012, Naguib et al., 2014). These materials have already shown great promise in various applications including electrochemical energy storage (Ahmed et al., 2017, Anasori et al., 2017, Jiang et al., 2018), water desalination (Ren et al., 2015), electromagnetic (Shahzad et al., 2016), catalysis (Ran et al., 2017), gas sensing (Kim et al., 2018) etc. Compared to other 2D materials, MXenes possess a unique combination of excellent electrical conductivity, hydrophilicity, potential for high density incorporation of several functional groups, ultrathin 2D sheet-like morphology as well as excellent ion intercalation behavior which are ideal for electrochemical sensing. So far, biosensors based on MXenes have been focused on the detection of nitrite, pesticides, phenol and H2O2 (Liu et al., 2015, Wang et al., 2015a, Wang et al., 2015b, Wu et al., 2018, Zhou et al., 2017). These biosensors used multilayered Ti3C2-MXene systems to immobilize electrochemical active proteins via physical adsorption. This method, although efficient, does not fully utilize the great potential of 2D nanosheet morphology of MXenes to incorporate a high density of surface functional groups. Thus, the sensing performance of physical adsorption methods is limited when detecting low concentration biomarkers, as required by applications such as cancer detection.

In order to evaluate the ultimate potential of MXenes for biosensing this paper proposed for the first time to use single/few-layered MXene (Ti3C2) nanosheets for covalent immobilization of bio-receptor (anti-CEA) for the cancer biomarker detection. Highly efficient electrochemical biosensors require highly active transducer surfaces that integrate the biomolecules efficiently while providing faster access to the analytes (Wang et al., 2017). In this context, the morphology of ultrathin 2D nanosheet of single/few layered Ti3C2-MXene with its high density of functional groups offers improved biomolecule loading and faster access to analyte. In addition, covalent immobilization of bio-receptor (enzymes, DNA, proteins, etc.) leads to not only improved uniformity and distribution, but also enables higher density of bound bio-markers that would result in enhanced biosensor performance (Wang et al., 2015d).

In this paper, amino groups are introduced on the surfaces of single/few- layered MXene (Ti3C2) nanosheets via chemical means for the covalent immobilization of bio-receptor. The resulting biofunctionalized MXene exhibits wide linear detection range towards carcinoembryonic antigen (CEA), an important cancer biomarker found in colorectal, lung, ovarian, pancreatic, breast and liver cancer patients (Hammarström, 1999, Kulpa et al., 2002, Myers et al., 1978, Wanebo et al., 1978). According to WHO report nearly half of all cancer deaths each year are associated with these cancers (WHO, 2018). Therefore, monitoring of CEA level may be an interesting alternative for clinical monitoring, prognosis, recurrence possibilities, and screening of hepatic metastases of cancers.

Section snippets

Materials

All biomolecules including carcinoembryonic antibody monoclonal (anti-CEA), carcinoembryonic antigen (CEA), bovine serum albumin (BSA) and human serum were procured from Sigma Aldrich, USA. Other chemicals including (3-Aminopropyl)triethoxysilane (Alfa Aesar, 98%), 1-ethyl-(dimethylaminopropyl)-carbodiimide hydrochloride (EDC, Sigma Aldrich), N-hydroxysuccinimide (NHS, Sigma Aldrich), lithium chloride (Sigma Aldrich) and buffer salts were of the analytical grade. Millipore purified De-ionized

Structural, morphological and elemental analysis

Fig. 1b shows the XRD pattern of the Ti3AlC2–MAX (pink curve), Ti3C2–MXene (orange curve) and f-Ti3C2-MXene (green curve), respectively. The XRD patterns of the MAX sample matches well with reported Ti3AlC2-MAX (JCPDS no. 052-0875) (Alhabeb et al., 2017). It is important to note that after exfoliation, the XRD peaks for Ti3C2–MXene exhibit broadening and significant loss of crystallinity due to the removal of aluminum. The broadened (002) peak decreases from 9.7° to 7.5°, indicating an increase

Conclusions

We have demonstrated a label-free and highly sensitive electrochemical biosensor for CEA detection, based on two-dimensional Ti3C2-MXene nanosheets. The Ti3C2-MXene nanosheets were synthesized by MILD method and uniformly functionalized with APTES for the covalent immobilization of anti-CEA. The fabricated bioelectrode (BSA/anti-CEA/f-Ti3C2-MXene/GC) exhibits a wider linear detection range of 0.0001–2000 ng mL−1 with sensitivity of ~ 37.9 µA ng−1 mL cm−2 per decade. The CEA concentration has

Acknowledgments

We thank Prof. Sahika Inal for providing the serum sample. Research reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST), Saudi Arabia and the University of Texas at Dallas, United States start-up fund.

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    Present address: DST INSPIRE Faculty, Centre for Nano Science and Engineering, Indian Institute of Science, Bangalore 560012, India

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