Carbon nanotube based electrochemical sensors for biomolecules

Review: Carbon nanotube based electrochemical sensors for biomolecules

Click on the title above to be taken to the full paper.

Abstract

Carbon nanotubes (CNTs) have been incorporated in electrochemical sensors to decrease overpotential and improve sensitivity. In this review, we focus on recent literature that describes how CNT-based electrochemical sensors are being developed to detect neurotransmitters, proteins, small molecules such as glucose, and DNA. Different types of electrochemical methods are used in these sensors including direct electrochemical detection with amperometry or voltammetry, indirect detection of an oxidation product using enzyme sensors, and detection of conductivity changes using CNT-field effect transistors (FETs). Future challenges for the field include miniaturizing sensors, developing methods to use only a specific nanotube allotrope, and simplifying manufacturing.

Keywords

Field effect transistor sensor;  Enzyme sensor;  Dopamine;  Virus;  Immunosensor;  Immunoglobulin

---

1. Introduction

The development of electrochemical sensors has been widely researched as an inexpensive method to sensitively detect a variety of biological analytes. Carbon based electrodes have been commonly used because of their low cost, good electron transfer kinetics and biocompatibility. Recently, carbon nanotubes (CNTs) have also been incorporated into electrochemical sensors. While they have many of the same properties as other types of carbon, CNTs offer unique advantages including enhanced electronic properties, a large edge plane/basal plane ratio, and rapid electrode kinetics. Therefore, CNT-based sensors generally have higher sensitivities, lower limits of detection, and faster electron transfer kinetics than traditional carbon electrodes. Many variables need to be tested and then optimized to create a CNT-based sensor. Electrode performance can depend on the synthesis method of the nanotube, CNT surface modification, the method of electrode attachment, and the addition of electron mediators. This review highlights different biomolecules and compares electrode design techniques for selective analyte detection.

The physical and catalytic properties make CNTs ideal for use in sensors. Most notably, CNTs display high electrical conductivity, chemical stability, and mechanical strength. The two main types of CNTs are single-walled CNTs (SWCNTs) and multi-walled carbon nanotubes (MWCNTs). SWCNTs are sp² hybridized carbon in a hexagonal honeycomb structure that is rolled into a hollow tube morphology [1]. MWCNTs are multiple concentric tubes encircling one another [2]. Numerous other CNT forms, such as double-walled CNTs [3], bamboo [4], and herringbone [5] have also been synthesized; CNT structure has been reviewed by Delgado et al. [6]. SWCNTs can be classified as either semi-conducting or metallic allotropes, depending on the chirality. The distinction of semi-conducting or metallic is important for their use in different sensors but the physical separation of allotropes has proven to be one of the more difficult challenges to overcome. In MWCNTs, a single metallic layer results in the entire nanotube displaying metallic behavior. More information on the physical and electronic structures can be found in the many published reviews [7] and [8].

Carbon nanotubes are primarily synthesized by three main techniques: arc discharge, laser ablation/vaporization, and carbon vapor deposition (CVD). In arc discharge the current through two graphite electrodes creates a deposit of CNTs on the cathode. By altering conditions either SWCNTs or MWCNTs can be synthesized. Laser vaporization of graphite in a silica tube lined, high temperature furnace generally results in MWCNTs, but with the use of catalytic metal nanoparticles, SWCNTs can be synthesized. MWCNTs are produced by CVD during the pyrolysis of hydrocarbon gases at high temperatures. Control of the synthesis parameters such as reagent gas, flow rate, temperature and metal catalysts allows for control of nanotube properties. Further information about CNT synthesis can be found in reviews of CNT synthesis and properties [9] and [10]. Most commercially available CNTs are formed by CVD. However, in application of CNTs the purity must be taken into account, as metal impurities may remain in the sample, even after some purification processes.

After synthesis, CNTs may be treated to functionalize their surfaces. The most common treatment with strong acids removes the end caps and may also shorten the length of the CNTs. Acid treatment also adds oxide groups, primarily carboxylic acids, to the tube ends and defect sites. Further chemical reactions can be performed at these oxide groups to functionalize with groups such as amides, thiols, or others. Altering the nanotube surface strongly affects solubility properties, which can affect the ease of fabrication of CNT sensors. Non-covalent functionalization by small molecules, grafting to or wrapping nanotubes with polymers or DNA can also alter the electrochemical properties of the material, as reviewed by Zhao and Stoddart [11]. A review by Balasubramanian discusses many of the functionalizations that have commonly been used [12]. The CNT ends and sidewall “defect” sites have been proposed to act similarly to pyrrolytic graphite edge planes and therefore have greater electrochemical activity [13]. Recent work however has contended that the sidewall may be responsible for electrochemical activity for SWCNTs [14] and [15]. Covalent and non-covalent sidewall and defect-site functionalizations have also been demonstrated to play a role in the electrocatalytic properties of CNTs.

CNTs, particularly CNT-field effect transistors (CNT-FETs), have been extensively developed as gas sensors [16]. The use of CNTs as sensors for biological molecules was pioneered by the Wang group, who developed a CNT-based electrode to detect the reversible oxidation of dopamine [17]. Intensive work has since been done to expand the use of CNTs as electrochemical sensors to realize the potential benefits of higher currents, lower overvoltages, and enhanced electron transfer rates. CNTs are commonly incorporated onto electrodes by directly growing CNTs on the electrode surface, adsorbing them on existing electrodes, imbedding them in polymer coatings, or combining CNTs and a binder to make a paste electrode. The common electrochemical methods used with CNT sensors include voltammetry, amperometry, electrical impedance spectroscopy, and potentiometry. Changes in resistance are also measured in field effect transistor (FET) sensors, where CNTs are used as the gate. To expand the array of analytes beyond just electroactive molecules, enzymes are often incorporated into biosensors to selectively detect an analyte and create an electroactive product after an enzymatic reaction. Biomolecules such as proteins, enzymes and DNA are easily adsorbed on to the surface of CNTs and can be attached directly to functional groups on the CNT. Many reviews have covered the development of electrochemical sensors using CNTs [18], [19],[20], [21], [22], [23] and [24].

Here, we present a critical review of recent research towards the development of CNT-based sensors for the detection of biological analytes. Because of the breadth of research that has been published in this area, we have limited this review to recent publications within the past three years, 2007–2009. While most reviews have been organized around different techniques to make sensors, we have chosen to organize this paper by type of analyte, so that different approaches to CNT sensors can be directly compared. We evaluate the detection of neurotransmitters, proteins, non-electroactive species by enzyme sensors, and DNA. Finally, some of the future challenges in the field are examined, including miniaturizing sensors, selecting specific types of nanotubes, and fine tuning the properties of CNT biosensors. Successfully optimizing and implementing CNT-based sensors is challenging; therefore, this promises to continue to be a fruitful area of research.

References associated with the above text. ALL references for this paper appear on the full paper.

[1] S. Iijima, T. Ichihashi, Nature, 363 (1993), pp. 603–605

[2] S. Iijima, Nature, 354 (1991), pp. 56–58

[3] S. Bandow, M. Takizawa, K. Hirahara, M. Yudasaka, S. Iijima, Chem. Phys. Lett., 337 (2001), pp. 48–54

[4] Y. Saito, T. Yoshikawa, J. Crystal Growth, 134 (1993), pp. 154–156

[5] N.A. Kiselev, J. Sloan, D.N. Zakharov, E.F. Kukovitskii, J.L. Hutchison, J. Hammer, A.S. Kotosonov, Carbon, 36 (1998), pp. 1149–1157

[6] J.L. Delgado, M.A. Herranz, N. Martin, J. Mater. Chem., 18 (2008), pp. 1417–1426

[7] M.S. Dresselhaus, G. Dresselhaus, A. Jorio, Ann. Rev. Mater. Res., 34 (2004), pp. 247–278

[8] E.T. Thostenson, Z.F. Ren, T.W. Chou, Compos. Sci. Technol., 61 (2001), pp. 1899–1912

[9] C.T. Kingston, B. Simard, Anal. Lett., 36 (2003), pp. 3119–3145

[10] M. Terrones, Int. Mater. Rev., 49 (2004), pp. 325–377

[11] Y.L. Zhao, J.F. Stoddart, Acc. Chem. Res., 42 (2009), pp. 1161–1171

[12] K. Balasubramanian, M. Burghard, Small, 1 (2005), pp. 180–192

[13] C.E. Banks, R.G. Compton, Analyst, 130 (2005), pp. 1232–1239

[14] I. Dumitrescu, P.R. Unwin, J.V. Macpherson, Chem. Commun. (2009), pp. 6886–6901

[15] K. Gong, S. Chakrabarti, L. Dai, Angew. Chem. Int., 47 (2008), pp. 5446–5450

[16] D.R. Kauffman, A. Star, Angew. Chem. Int., 47 (2008), pp. 6550–6570

[17] P.J. Britto, K.S.V. Santhanam, P.M. Ajayan, Bioelectrochem. Bioenerg., 41 (1996), pp. 121–125

[18] J.J. Gooding, Electrochim. Acta, 50 (2005), pp. 3049–3060

[19] L. Agui, P. Yanez-Sedeno, J.M. Pingarron, Anal. Chim. Acta, 622 (2008), pp. 11–47

[20] M. Trojanowicz, Trac-Trends Anal. Chem., 25 (2006), pp. 480–489

[21] J. Wang, Electroanalysis, 17 (2005), pp. 2005–2007

[22] Y.H. Yun, Z.Y. Dong, V. Shanov, W.R. Heineman, H.B. Halsall, A. Bhattacharya, L. Conforti, R.K. Narayan, W.S. Ball, M.J. Schulz, Nano Today, 2 (2007), pp. 30–37

[23] A. Merkoci, Microchim. Acta, 152 (2006), pp. 157–174

[24] G.A. Rivas, M.D. Rubianes, M.C. Rodriguez, N.F. Ferreyra, G.L. Luque, M.L. Pedano, S.A. Miscoria, C. Parrado, Talanta, 74 (2007), pp. 291–307