Potential diagnostic applications of biosensors: current and future directions

Abstract

This review describes recent advances in biosensors of potential clinical applications. Biosensors are becoming increasingly important and practical tools in pathogen detection, molecular diagnostics, environmental monitoring, food safety control as well as in homeland defense. Electrochemical biosensors are particularly promising toward these goals arising due to several combined advantages including low-cost, operation convenience, and miniaturized devices. We review the clinical applications of electrochemical biosensors based on a few selected examples, including enzyme-based biosensors, immunological biosensors and DNA biosensors.

Figure 1

A ruthenium-labeled maltose-binding protein (MBP) is site specifically attached to a self-assembled monolayer (SAM) coated gold electrode. The protein-ligand binding process mediates dependent changes between the Ru(II) redox reporter group and the surface-modified gold electrode, which thereby alters current flow between the two components. Reprinted with permission from Benson DE, Conrad DW, de Lorimier RM, et al. 2001. Design of bioelectronic interfaces by exploiting hinge-bending motions in proteins. Science, 293:1641–4. Copyright 2001 © AAAS.

Figure 2

(A) Assembly of Au-NPreconstituted GOx electrode by (a) the adsorption of Au-NPreconstituted GOx to a dithiol monolayer associated with a Au electrode and (b) the adsorption of Au-NPs functionalized with FAD on the dithiol-modified Au electrode followed by the reconstitution of apo-GOx on the functional NPs (16). (B) A STEM image of GOx reconstituted with the Au-FAD hybrid NP. Arrows show Au clusters. Reprinted with permission from Xiao Y, Patolsky F, Katz E, et al. 2003. Plugging into enzymes: nanowiring of redox enzymes by a gold nanoparticle. Science, 299:1877–81. Copyright 2003 © AAAS.

Figure 3

Schematic diagram of HSA sandwich assay procedure. Reprinted with permission from Yu X, Kim SN, Papadimitrakopoulos F, et al. 2005. Protein immunosensor using single-wall carbon nanotube forests with electrochemical detection of enzyme labels. Mol Biosyst, 1:70–8. Copyright 2003 © Royal Society of Chemistry.

Figure 4

A stem loop oligonucleotide possessing terminal thiol and a ferrocene group is immobilized at a gold electrode through self-assembly. In the absence of target, the stem loop structure holds the ferrocene tag into close proximity with the electrode surface, thus ensuring rapid electron transfer and efficient redox of the ferrocene label. On hybridization with the target sequence, a large change in redox currents is observed, presumably because the ferrocene label is separated from the electrode surface. Reprinted with permission from Fan C, Plaxco KW, Heeger AJ. 2003. Electrochemical interrogation of conformational changes as a reagentless method for the sequence-specific detection of picomolar DNA. Proc Natl Acad Sci U S A, 100:9134–7. Copyright 2003 © The National Academy of Sciences of the United States of America.