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We have made an effort to provide a comprehensive overview on the emerging synergy between implantable electrochemical biosensors and nanotechnology

Emerging synergy between nanotechnology and implantable biosensors: a review.

Biosensors and Bioelectronics, no. 7 (2010): 1553-1565

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摘要

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. Thi...更多

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简介
  • Numerous clinical trials and intensive research efforts have indicated that continuous metabolic monitoring holds great potential to provide an early indication of various body disorders and diseases.
  • While the nature of the reported improvement from the use of nanostructured materials is still under debate, a number of implantable devices have started to employ such nanostructuring of their outer membrane surface to alleviate foreign body response (Ainslie et al, 2008).
重点内容
  • Numerous clinical trials and intensive research efforts have indicated that continuous metabolic monitoring holds great potential to provide an early indication of various body disorders and diseases
  • The development of biosensors for the measurement of metabolites has become an area of intense scientific and technological studies for various research groups across the world. These studies are driven by the need to replace existing diagnostic tools, such as glucose test strips, chromatography, mass spectroscopy and enzyme linked immunosorbent assays (ELISA), with faster and cost effective diagnostic devices that have the potential to provide an early signal of metabolic imbalances and assist in the prevention and cure of various disorders like diabetes and obesity
  • Implantable biosensors form a highly desirable proposition for diabetes management which at present rely on data obtained from test strips using blood drawn from finger pricking, a procedure that is painful and is incapable of reflecting the overall direction, trends, and patterns associated with daily habits (Reach and Wilson, 1992)
  • This initiated wide research efforts focused on developing implantable biosensors for continuous monitoring of various biologically relevant metabolites (Wang, 2001)
  • This review aims to survey the current status of implantable biosensors with particular emphasis on advances based on nanotechnology
  • We have made an effort to provide a comprehensive overview on the emerging synergy between implantable electrochemical biosensors and nanotechnology
结果
  • The unique electrical properties of 1-D nanomaterials like carbon nanotubes (Allen et al, 2007; Besteman et al, 2003), nanorods (Kang et al, 2007; Wei et al, 2006), nanowires (Wang et al, 2008b) and semiconducting polymers (Forzani et al, 2004; Yoon et al, 2008) have led researchers to utilize them as channel materials and develop sensors based on changes induced in either gate conductance, modulation, transconduction, hysteresis or threshold voltage (Fig. 2c).
  • The sensitivity of implantable biosensor is dependent on: (i) physical design, (ii) activity of the enzyme, (iii) surface activity of the working electrode, (iv) inner polymer membranes that are used to either immobilize enzymes or eliminate interferences (McMahon et al, 2005), and (v) the presence of an outer membrane required to alleviate oxygen dependence and/or to prevent biofouling (Vaddiraju et al, 2008; Yu et al, 2006a).
  • Surface modification of the working electrodes with platinum and gold nanoparticles (Li et al, 1998; Somasundrum et al, 1996), SWNTs (Gooding, 2005; Liu et al, 2007b; Sherigara et al, 2003; Tang et al, 2004; Wang, 2005; Yu et al, 2003a), multi-walled carbon nanotubes (MWNTs) (Dai and Shiu, 2004; Qu et al, 2004; Salimi et al, 2007) and combinations thereof (Luque et al, 2006; Male et al, 2007; Wang and Zhang, 2001) has been shown to alleviate both these issues and improve sensitivity at low operating potentials.
  • The issue of low sensor selectivity arises from the fact that the high potential (i.e. 0.6–0.7 V vs Ag/AgCl reference electrode) required for electrochemical oxidation of enzymatically generated H2O2 in most implantable biosensors promotes the oxidation of many endogenous species (such as ascorbic acid (AA), uric acid (UA), acetaminophen (AP), dopamine, and NO) rendering the sensor response erroneous.
  • Whatever the reason might be, such nanostructured supports for enzyme immobilization could be a potential vehicle to enhance implantable biosensor lifetime and modify device architecture to alleviate some of the issues discussed earlier in this review.
结论
  • Keeping in mind the high cost involved in the design of nanoelectrodes, Karyakin et al (2009) have employed nanostructuring of the enzyme layer rather than the working electrodes and have achieved a two orders of magnitude lower detection limit (10−9 nm of H2O2) without a decrease of sensitivity compared to sensor with no enzyme nanostructuring.
  • Various kinds of nanoparticles, nanotubes and nanowires have been used to improve basic biosensor parameters such as sensitivity, selectivity
总结
  • Numerous clinical trials and intensive research efforts have indicated that continuous metabolic monitoring holds great potential to provide an early indication of various body disorders and diseases.
  • While the nature of the reported improvement from the use of nanostructured materials is still under debate, a number of implantable devices have started to employ such nanostructuring of their outer membrane surface to alleviate foreign body response (Ainslie et al, 2008).
  • The unique electrical properties of 1-D nanomaterials like carbon nanotubes (Allen et al, 2007; Besteman et al, 2003), nanorods (Kang et al, 2007; Wei et al, 2006), nanowires (Wang et al, 2008b) and semiconducting polymers (Forzani et al, 2004; Yoon et al, 2008) have led researchers to utilize them as channel materials and develop sensors based on changes induced in either gate conductance, modulation, transconduction, hysteresis or threshold voltage (Fig. 2c).
  • The sensitivity of implantable biosensor is dependent on: (i) physical design, (ii) activity of the enzyme, (iii) surface activity of the working electrode, (iv) inner polymer membranes that are used to either immobilize enzymes or eliminate interferences (McMahon et al, 2005), and (v) the presence of an outer membrane required to alleviate oxygen dependence and/or to prevent biofouling (Vaddiraju et al, 2008; Yu et al, 2006a).
  • Surface modification of the working electrodes with platinum and gold nanoparticles (Li et al, 1998; Somasundrum et al, 1996), SWNTs (Gooding, 2005; Liu et al, 2007b; Sherigara et al, 2003; Tang et al, 2004; Wang, 2005; Yu et al, 2003a), multi-walled carbon nanotubes (MWNTs) (Dai and Shiu, 2004; Qu et al, 2004; Salimi et al, 2007) and combinations thereof (Luque et al, 2006; Male et al, 2007; Wang and Zhang, 2001) has been shown to alleviate both these issues and improve sensitivity at low operating potentials.
  • The issue of low sensor selectivity arises from the fact that the high potential (i.e. 0.6–0.7 V vs Ag/AgCl reference electrode) required for electrochemical oxidation of enzymatically generated H2O2 in most implantable biosensors promotes the oxidation of many endogenous species (such as ascorbic acid (AA), uric acid (UA), acetaminophen (AP), dopamine, and NO) rendering the sensor response erroneous.
  • Whatever the reason might be, such nanostructured supports for enzyme immobilization could be a potential vehicle to enhance implantable biosensor lifetime and modify device architecture to alleviate some of the issues discussed earlier in this review.
  • Keeping in mind the high cost involved in the design of nanoelectrodes, Karyakin et al (2009) have employed nanostructuring of the enzyme layer rather than the working electrodes and have achieved a two orders of magnitude lower detection limit (10−9 nm of H2O2) without a decrease of sensitivity compared to sensor with no enzyme nanostructuring.
  • Various kinds of nanoparticles, nanotubes and nanowires have been used to improve basic biosensor parameters such as sensitivity, selectivity
基金
  • Financial support for this study was obtained from US Army Medical Research Grants (#DAMD17-02-1-0713, #W81XWH04-1-0779, #W81XWH-05-1-0539 and # W81XWH-07-10668), NIH/NHLBI 1-R21-HL090458-01, AFOSR FA9550-09-1-0201, NSF CBET-0828771/0828824, NIH ES013557, Telemedicine and Advanced Technology Research Center (TATRC) at the U.S Army Medical Research and Materiel Command (USAMRMC) (Award No W81XWH-09-1-0711) and National Institute of Biomedical Imaging & Bioengineering award (R43EB011886)
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