Introduction and Background

A typical biosensor design includes three main parts: target recognition elements, signal transduction elements, and signal amplification elements (not always required) (McNaught et al. 1997). Among these three components, the target recognition element is the key to contact, detect, and recognize useful medical signals for further analysis and diagnosis. More importantly, using functional biomaterials as recognition elements enhances the sensitivity, selectivity, stability, and lifetime of a biosensor. Today, biological engineering has created a variety of biomaterials for sensor applications. Such materials can be either natural biological components (such as tissues, microorganisms, organelles, cell receptors, enzymes, antibodies, and nucleic acids) (Xia et al. 2010; McLaughlin et al. 2010; Guo et al. 2010) or biologically derived materials (so-called biomimetic materials) (Lin et al. 2010;

Department of Orthopaedics, School of Engineering, Brown University, 184 Hope Street, Providence, RI 02917, USA e-mail: [email protected]

T.J. Webster (ed.), Nanotechnology Enabled In situ Sensors for Monitoring Health, 75

DOI 10.1007/978-1-4419-7291-0_4, © Springer Science+Business Media, LLC 2011

Huang et al. 2010; Bi et al. 2006). For example, deoxyribonucleic acid (DNA) or DNA-derived materials are receiving intensive attention for biosensor applications.

Because DNA itself is highly selective in base-pairing interactions between complementary sequences and DNA contains the genetic instructions used in the development and functioning of all known living organisms, they are valuable for diagnosis and are relatively easy to be specifically detected. As an example, single-stranded DNA was immobilized on a biosensor probe, where base-pairing interactions were recognized and hybridized with a target DNA to the surface to release signals, and such signals were recorded and analyzed for diagnosis, as shown in Fig. 1. A signal can be reported optically, mechanically, or electrochemically. For instance, in an optical method, gold nanoparticles modified with single-stranded DNA change color during the hybridization of the target DNA and immobilized DNA (Storhoff et al. 1998). Another widely used method involves electrochemical detection. Because electrochemical reactions (such as oxidation and reduction) contain an electron transition process, such processes result in electrical signals. Such signals can be detected directly to save an expensive signal transduction system and increase the sensitivity of diagnosis. There are two detection mechanisms: one is hybridization-based DNA detection as mentioned above and the other is enzymatic-based DNA detection. For the enzymatic-based DNA detection, DNA-related enzymes are introduced into the biological recognition system and changes in the amount of these enzymes correlate to specific biological processes (such as the deletion or fusion of the target DNA). For example, when a sensor experiences a specific process, the enzyme level either increases or decreases, resulting in amplification or reduction of the signal. The enzymatic process is highly specific to a DNA sequence, which makes it ideal for DNA mismatch detection, as shown in Fig. 2 (Wei et al. 2010).

Target DNA

Target DNA

Signaltransduction and analysis

DMA probe of a biosensor

Fig. 1 A schematic DNA nanotechnology biosensor design. Target DNA is captured at the DNA probe and the resulting signal is transduced for analysis (adapted and redrawn from Drummond et al. (2003))

a Cleavage of DNA b Cleavage of DNA

Direct detection via reporting molecule

Fig. 2 Electrochemically based DNA nanotechnology sensors for protein analytes. (a) Direct detection after specific DNA enzymatic process. (b) Detection of extralabeled reporter after specific DNA enzymatic process (adapted and redrawn from Wei et al. (2010))

Traditionally, DNA-based biosensors do not interact with the biological system during the detection process and are known as "passive" sensors. They are usually used to detect the target molecules in samples collected from host biological systems. However, in surgical applications, it is often difficult to collect samples from inspected organs or tissues. Especially, surgeons sometimes need to monitor the target organ or tissue to diagnose diseases or evaluate the efficacy of a surgery. In this manner, the "passive" DNA-based sensors cannot satisfy the need of surgical diagnosis. Therefore, a novel emerging technique, in situ biosensors, has been developed for various surgical applications (Leegsma-Vogt et al. 2004; Wilkins and Atanasov 1996). For instance, a biosensor technique, called electromyography, has been used to analyze and diagnose muscle or nerve functions inside body conditions (Hoch and Zieve 2008). Thin electrodes are placed in soft tissues to help analyze and record electrical activity in the muscles. Another field where biosensors are widely used in surgical diagnosis is orthopedics. A telemetric device for orthopedic implants has been invented for "real time" diagnosis. Typically, the telemetry system with a small implantable transmitter uses wireless communication with an external computer system. The data are transmitted at high frequency or radio-frequency pulses, as shown in Fig. 3 (Durr et al. 1999; Graichen and Bergmann 1991; Graichen et al. 1999). Basically, the semiconductor strain gauges are placed at the inner circumference of the neck of an orthopedic implant cavity. A small loop antenna outside the implant (the pacemaker is fed through and forms a single loop antenna outside the Ti at one end of the implant) is used to transmit the radio-frequency pulses to the external receiving antenna. The radio-frequency receiver of the external device (TELEPORT, as shown in Fig. 3) is connected to a microcontroller to analyze the measured voltages. Finally, computer software interprets the data sent from the microcontroller to display the real-time load components. In addition, researchers have also focused on using DNA-based biosensors to rapidly detect tumor cells or cancer markers in the blood or tissues (de la Escosura-Muniz et al. 2009; Henry et al. 2009). Importantly, an implantable biosensor has already been developed for cancer diagnosis in tissues (Daniel et al. 2009).

Fig. 3 Block diagram of the implantable telemetry system for measuring the implant load (adapted from Graichen et al. (2007))

However, to be a successful biosensor for surgical diagnosis, the main challenge is the target recognition material of the sensor. First of all, diagnosis agents (for example, DNA) must be immobilized onto biosensors with proper functionality and stability. Depending on the application and sensor material, a variety of approaches have been developed to synthesize and functionalize DNA onto biosensors.

This topic is stressed in Sect. 2 of this chapter. Moreover, for implantable biosensors in surgeries, a continuous concern is the biocompatibility of the sensor materials (Vaddiraju et al. 2010). Bio-incompatible sensors may result in the activation of the immune system, chronic inflammation, and formation of granulation tissue. Such reactions cause damage to the host tissue, as well as greatly decrease the lifetime and accuracy of the sensors. To overcome this gap, researchers intend to combine nanotechnology with bioengineering knowledge to produce novel DNA-derived materials with excellent biocompatibility and multifunctionality. This topic is discussed in Sect. 3. Therefore, the following chapter is filled with two types of materials for biosensor applications: natural DNA and DNA-derived materials, pointing out a way to combat current challenges and illustrating future prospects of DNA-based nanotechnology biosensors for surgical applications.

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