The Preferred Biotech Resource in Asia-Pacific
Vol 19, No 07, July 2015
Biotech in China
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Graphene for Smart Medical Devices
Priscilla Kailian Ang, Wong Cheng Lee, Kian Ping Loh & Chwee Teck Lim
National University of Singapore

Being the cornerstone of all living organisms, the living cell determines health and sickness, life and death. Therefore, designing an autonomous wearable or implantable smart medical device (SMD) that obtains information from such living entities and conveys it to electronic systems to assist, augment or restore impaired cognitive, cardiac, motor and homeostatic functions holds key to the betterment of mankind – all within the size range of a living cell. In this respect, having a single carbon nanomaterial that could boost performance in the size, operational, communication and energy aspects of such an SMD is highly desirable. In fact, since 2004, scientists are steadily fulfilling this goal with graphene, a two-dimensional, single-atom-thick sheet of sp2 hybridized carbon nanomaterial.

The key question is: how does graphene aid in the development of SMD? Graphene, amidst its carbon counterparts such as fullerene, CNT and diamond, displays superior functionalities stemming from its versatility to tune its electronic, electrochemical, optical, mechanical and thermal properties simply by modifying the lateral dimension, number of layers, stiffness, defect density and chemical composition. This gives rise to various graphene-related materials, such as graphene quantum dots (Lu et al., 2011), graphene nanoparticles (Li et al., 2012), graphene nanoribbon (Parashar et al., 2011), graphene nanosheets (Zhang et al., 2011), few-layer graphene and chemically processed graphene (Ang et al., 2009), which can boost the performance, biocompatibility and chemical stability of SMDs. The striking advantages of pristine graphene hinge on its atomic structure, giving rise to its two-dimensionality, atomic thinness and high electrical conductivity – properties which are advantageous for scaling of nanoelectronic devices (Schwierz 2010). On the other hand, from a chemist’s viewpoint, graphene is a giant “poly-molecule” amenable to a library of chemical reactions (Loh et al., 2010), resulting in composite hybrid materials possessing novel physical, chemical and electrical properties. By tuning its lateral dimension and chemical functional groups, graphene can be used in a broad spectrum of biomedical and engineering applications.

Here, we place a central focus on how graphene can be incorporated in an autonomous SMD. In particular, we witness how the unique properties of graphene and graphene-related materials, such as biocompatibility, chemical stability, mechanical robustness, conformity, lightweight, optical transparency, high surface area, electrical sensitivity, energy storage and harvesting capabilities, bear pivotal importance for the advancement of SMDs.

Sensing applications of graphene

A sensor converts an external physical stimulus, which can take the form of a chemical (ions and molecules), electrical (potential gradient), optical (luminescence) or thermal change, into a distinguishable and processable signal. The fundamental sensitivity limit of the sensor hinges on the intimate coupling with bio-entities and the signal-to-noise ratio. Graphene and its derivatives establish excellent communication between biotic and abiotic system because of its stable interaction with bio-entities (e.g. DNA, lipids, proteins and cells) (Lu et al., 2012; Ryoo et al., 2010; Singh et al., 2012), high adsorption capacity for biorecognition proteins and target molecules (Zhang et al., 2011), and high sensitivity since every carbon atom in graphene responds to changes induced by bio-entities enabling single molecule detection such as each nucleobase in deoxyribonucleic acids (DNA) (Merchant et al., 2010). In particular, graphene accurately detects the presence of electrically charged and electroactive bio-entities (Dong et al., 2010), enables fluorescence molecular detection (Shen et al., 2012), responds precisely to changes in the ionic environment of the cell specific to cellular activity such as the electrical activity of beating cardiomyocytes (Cohen-Karni et al., 2010) and forms a stable interface with neuronal cells (Heo et al., 2011). Capitalizing on the electrical sensitivity of graphene, harmful micro-organisms (Mannoor et al., 2012) and diseased cells (Swierczewska et al., 2012) are also detected. These attributes reinforce the unique selling point of graphene as the sensor unit in SMD.

Graphene electronic circuits

The intelligence of the autonomous SMD is derived from the memory and logic components, which are responsible for data processing, information storage and communication with external devices. As memory and logic devices are expected to be scaled to smaller dimensions and yet achieve nonvolatile memory, large storage density, fast switching speed, high-fidelity transmission of information and low power consumption with minimal heat generation, the scaling and performance of current devices are hitting fundamental limits. However, graphene offers new hopes as performance improvements with added device flexibility are evident for graphene-based memory and logic devices (Sordan et al., 2009; Jeong et al., 2010). On the other hand, wireless communication is an essential feature of SMDs and having an ultra-small communication system is desirable for wireless body area network (BAN). A basic wireless communication system consists of a transmitter and receiver, with the most common operational electromagnetic wavelength in the radio frequency (RF) range.

Graphene has made significant strides in RF communications (Moon et al., 2012). Unlike organic semiconductors plagued by low carrier mobility, graphene is good for high frequency low noise amplifiers (Das et al., 2011), which are used for fast communicating devices with low power consumption. The ambipolarity of graphene is also explored in RF mixed-signal applications such as full wave rectifiers (Han et al., 2009), frequency multipliers (Han et al., 2010) and mixers (Han et al., 2010). Prior to the discovery of graphene, these RF mixed-signal applications would require a full bridge circuit and several conventional diodes (Sung-Yong et al., 2006) for zero-volt rectification (Palacios et al., 2010). Besides facilitating a wireless sensing readout, in which changes in conductance can be correlated to changes in frequency and bandwidth of the sensor resonance, RF communication also enables battery-free powering of the SMD by inductive coupling between RF antennas and transmitters (Mannoor et al., 2012). Recently, the terahertz (1012 Hz or THz) region is gaining interest. With relatively small wavelengths in the millimeter to micrometer range, antennas built on THz technology will dramatically decrease in size. Electrically tunable THz modulation is of particular advantage in wireless communications and this can be easily achieved by graphene, unlike metal gates. Besides modulating THz transmission, graphene plasmons are more easily tunable than metallic ones, thus enables frequency selection of optical antennas with the added advantage of stronger electric field enhancement factor (Liu et al., 2012). Additionally, THz radiation is found to be emitted from the electron-hole plasma in optically pumped graphene and this makes graphene a viable source for THz emission (Prechtel et al., 2012).

Graphene-based energy sources

Continuous monitoring systems built into SMDs heavily rely on a continuous supply of energy for long-term powering. Other than conventional energy sources such as batteries and supercapacitors (Sun et al., 2011), emerging technologies that derive energy from body fluids (e.g. graphene-based biofuel cells (Sharma et al., 2011)), body heat (e.g. graphene-based thermoelectric generators (Xiao et al., 2011)) and body movements (e.g. graphene-based piezoelectric generators (Ong et al., 2012)) are also viable energy sources. Because the size of SMDs is mainly constrained by the size of their energy sources, approaches that can scale energy sources and deliver higher power density are been actively pursued. Graphene is positioned as a key material for this quest. Being extremely light and thin, it could deliver the highest gravimetric energy density (J/g) and the highest volumetric energy density (J/cm3), respectively. The energy storage capability of graphene and its derivatives has been capitalized in the construction of lithium (Li) ion batteries and supercapacitors. The two-dimensional membrane structure, flexibility, electrical conductivity and chemical versatility, coupled with easy integration with nanoparticles (Wu et al., 2012) or nanopillars (Ji et al., 2011) and easy engineering of porosity (Zhao et al., 2011) resulting in high in-plane and edge defect density, are attributes of graphene to create Li ion batteries that exhibit highly reversible specific capacity, enhanced rate capability and charge/discharge cycling stability, with added incentives of flexibility and printability (Wei et al., 2011). Graphene and its related materials are particularly attractive for a battery-supercapacitor hybrid energy source since they can be chemically functionalized to increase surface area for charge storage (Brownson et al., 2011).

It is highly desirable to create a miniaturized and autonomous graphene-based system-on-a-chip SMD that could periodically check the health of cells and report cellular activities to an external monitoring system to prevent the onset of diseases and improve the quality of life. We believe that scaling of a fully functional and flexible system comprising the sensing electrode, memory and logic unit, communication antennas and transmitters as well as energy sources could be realized with the incorporation of graphene. Graphene bioelectronics will certainly revolutionize the landscape of electronics and the medical industry in the years to come.

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