Emerging synergy between nanotechnology and implantable biosensors: a review

Abstract

The development of implantable biosensors for continuous monitoring of metabolites is an area of sustained scientific and technological interests. On the other hand, nanotechnology, a discipline which deals with the properties of materials at the nanoscale, is developing as a potent tool to enhance the performance of these biosensors. This article reviews the current state of implantable biosensors, highlighting the synergy between nanotechnology and sensor performance. Emphasis is placed on the electrochemical method of detection in light of its widespread usage and substantial nanotechnology based improvements in various aspects of electrochemical biosensor performance. Finally, issues regarding toxicity and biocompatibility of nanomaterials, along with future prospects for the application of nanotechnology in implantable biosensors, are discussed.

Figure 1

(a) Sequence of events that are initiated around an implant leading to the formation of fibrous capsules around implantable systems (Frost and Meyerhoff 2006). (Reprinted with permission from American Chemical Society) (b) Various failure mechanisms reported for an implantable biosensor (Wisniewski and Reichert 2000). (Reprinted with permission from Elsevier)

Figure 2

(a) Schematic representation of a nanotube field-effect transistor (NTFET) device (Allen et al. 2007); (b) Schematic of a typical organic electrochemical transistor along with a typical reaction of interest that is utilized at the gate electrode (Bernards et al. 2008); (c) Typical NTFET transfer characteristic (source–drain conductance vs gate voltage) that can be used to measure analyte concentrations. (i) Maximum conductance, (ii) modulation, (iii) transconductance, iv) hysteresis, and (v) threshold voltage (Allen et al. 2007). (Figures 2a and c are reprinted with permission from Wiley VCH from reference; Figure 2b is reprinted with permission from Royal Society of Chemistry)

Figure 3

(a) Illustration of the proof-of-concept BioMEMS sensors based on polymeric substrates rolled up to form a catheter, wherein the sensing element is located on the inner walls of the rolled-up catheter. (b) Structure and working principle of glucose sensor showing the three electrodes and bent active region (Li et al. 2007). (Reprinted with permission from Elsevier)

Figure 4

Schematic cross section of the first generation and second generation oxidase- based glucose biosensors, along with relevant reactions needed to afford electrochemical detection.

Figure 5

Schematic cross section of a third generation of biosensors specifically shown for glucose oxidase-based glucose detection.

Figure 6

Schematic cross section of (a) a typical one dimensional sensor where glucose and oxygen both diffuse in the same direction, mainly perpendicular to the plane of the electrode and (b) a two dimensional sensor, where glucose and oxygen diffuse axially into the enzyme gel but only oxygen can diffuse radially into the gel through the hydrophobic membrane (Gough et al. 1985). (Reproduced with permission from American Chemical Society)

Figure 7

(a) Various steps in the fabrication of a glucose biosensor based on carbon nanotube nanoelectrode ensembles: (i) Electrochemical treatment of the carbon nanotube NEEs for functionalization (ii) Coupling of the glucose oxidase (GOx) enzyme to the functionalized carbon nanotube NEEs. (b) Response of the carbon nanotube based glucose biosensors to 5 mM addition of glucose (G), followed by 0.5 mM additions of each of: ascorbic acid (AA), uric acid (UA) and acetaminophen (AC) operating at −0.2 V vs Ag/AgCl reference electrode (Lin et al. 2004). (Reprinted with permission from American Chemical Society.)