Nano Today
ReviewNanostructure-based electrical biosensors
Introduction
The development of exquisite nanofabrication tools and techniques in conjunction with the discovery of novel nanomaterials has imparted momentum to the fabrication of functional nanostructure-based devices. For example, ever since its introduction by Bell Laboratories in 1975, electron-beam lithography (EBL) has emerged as one of the most widely accepted techniques for making features in the nanometer regime [1]. Coupled to advanced electron microscope, today's direct-write EBL systems can potentially generate <10-nm features, a dramatic improvement over the 1-μm features reported by T.J. Watson Research Center in 1978 [2]. Focused ion beam (FIB), developed by Hughes Research Laboratories, primarily used for site-specific analysis, deposition, and ablation of materials [3], has been proven to be very useful in the fabrication of micro- and nanostructures mainly because of its ability to selectively remove and deposit materials without the use of a patterned mask [4], [5]. Lately, other techniques have been invented for generating nanopatterns, among them nano-imprint lithography (NIL) marks a difference because of its low cost, high throughput, and high resolution [6]. This inherently three-dimensional patterning process has been used to fabricate metal-oxide-semiconductor field-effect transistors, organic thin film transistor, as well as sub-10 nm self-enclosed nanofluidic channel arrays used in DNA stretching experiments [7], [8], [9], [10].
With a rich inventory of nanomaterials and nanofabrication techniques, new avenues have been opened up in the field of biosensors. Researchers around the globe have been tailor-making a multitude of nanostructure-based biosensors and devising new protocols to harness them for ultrasensitive biosensing applications. Biological events occurring at the surface of nanomaterials result in unique modes of signal transduction, not discernible at a bulk structure of the same material. Owing to the presence of a much larger number of atoms or molecules on the material surface, most of the atoms are capable of transducing an event occurring at the interface or in the vicinity. Thus, a higher shift from the baseline physical properties is expected from nanomaterials and the nanostructure-based devices than from their bulk counterparts. In this paper, we intend to review some of the major advances in the field of nanostructure-based biosensors. Though NEMS devices will be outlined, we will emphasize on electrical sensing that offers the possibility of portable assays in a variety of point-of-care environments. Representative examples in each section will be provided to illustrate the principle of operation of a particular class of devices. Critical issues like non-specific binding (NSB), sensitivity, selectivity, and limit of detection (LOD) will be addressed, whenever appropriate.
Section snippets
SWCNT-based field-effect biosensor
Recent interests in quasi-one dimensional (Q1D) nanomaterial-based devices for chemical [11], [12] and biological sensing applications [13], [14], [15] are motivated by their ultrasmall sizes, high surface-to-volume ratios and unique physicochemical properties, which differ markedly from their bulk counterparts. As an extensively investigated case, SWCNT-based field-effect transistors (FETs) were first discussed in this review. A field-effect device relies on an electrical field to control the
Semiconducting nanowire-based FET biosensor
In recent years, there has been a surge in research interest in exploiting biosensing devices based on semiconducting nanowires. Even though SWCNT possesses certain inherent morphological and electrical uniqueness, limitations in controlling orientation, chirality, and electronic band structure might lag it behind the semiconducting nanowires for biosensing applications. Semiconducting nanowires can be synthesized with high reproducibility. And they offer a rich chemistry and leave enough scope
Nanogap, nanochannel, and NEMS-based biosensor
Although nanostructured devices based on the Q1D materials have been studied most extensively in the past decade, there are other nanostructures that have also been explored for possible biosensing applications. We start our discussion with nanogap biosensors, which primarily depend on the modulation of the conductance or capacitance upon the introduction of biological species. A nanogap biosensor usually consists of two electron-conducting electrodes separated by an insulating gap/layer of
Concluding remarks and future outlook
Recent advancements in nanotechnology have enabled a paradigm shift in biosensing. In this review, we made an attempt to create a collage of thumbnail pictures of such promising nanostructure-based biosensors. From the gamut of literature in our collection we noticed that many researchers have reported the potential application of the nanostructure-based biosensors in the detection of biological species featuring direct electrical transduction. And, in particular, the SWCNT and semiconducting
Acknowledgement
This work was supported by the Institute of Bioengineering and Nanotechnology under the Agency for Science, Technology and Research (A*STAR), Singapore.
Dr. Somenath Roy is a Research Scientist in the Biosensors and Biodevices Group at the Institute of Bioengineering and Nanotechnology, Singapore. He received his PhD degree in Materials Science and Engineering from Indian Institute of Technology, Kharagpur in 2004. In the same year, he received a postdoctoral fellowship from Swedish Research Council and joined Swedish Sensor Center, Linköping, Sweden. During 2005–2007 he worked as a Coordinator, Research Programs at Florida International
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Dr. Somenath Roy is a Research Scientist in the Biosensors and Biodevices Group at the Institute of Bioengineering and Nanotechnology, Singapore. He received his PhD degree in Materials Science and Engineering from Indian Institute of Technology, Kharagpur in 2004. In the same year, he received a postdoctoral fellowship from Swedish Research Council and joined Swedish Sensor Center, Linköping, Sweden. During 2005–2007 he worked as a Coordinator, Research Programs at Florida International University, Miami, FL, USA. His present research endeavor is focused on fabrication of micro-/nanoscale sensing platforms for ultrasensitive detection of proteins and nucleic acids.
Dr. Zhiqiang Gao is a Group Leader of the Biosensors and Biodevices Group, the Institute of Bioengineering and Nanotechnology (IBN). He received his BSc and PhD in Chemistry from Wuhan University, China. The following years he worked as a postdoctoral fellow at Åbo Akademi University and The Weizmann Institute of Science. He spent three years at various institutions in the United States before joining IBN in December 2002. Research in his group currently includes ultrasensitive biosensors for nucleic acids and proteins, synthesis of multifunctional biotags and the design of DNA-targeted agents.