Ajit Sadana

Binding and Dissociation of Biomarkers for Alzheimer's Disease on Biosensor Surfaces

Dementia is a loss of brain function that may occur with certain diseases. Alzheimers disease (AD) is one form of dementia. AD worsens with time, and it affects memory, thinking, and behavior (PubMed Health, 2011). These authors indicate that as one grows older the risk of developing AD goes up. These authors emphasize that AD is not a part of the normal aging process. The risk of AD increases if a close blood relative (such as a brother, sister, or parent) has it. These authors further indicate that AD may be characterized as early onset and late onset. Early onset of AD occurs before 60 years of age, and late onset of AD develops in people of 60 years of age and older. AD may be briefly described in undergoing three stages: (1) early symptoms (misplacing items, getting lost in familiar routes, etc.), (2) “intermediate stage” symptoms (forgetting details about current events, difficulty in reading and writing, etc.), and (3) severe AD symptoms (can no longer understand language, recognize family members, or perform daily living activities).

Binding and Dissociation of Biomarkers for Systemic Lupus Erythematosus

A fractal analysis is presented for the kinetics of binding and dissociation of systemic lupus erythematosus (SLE) biomarkers and other autoimmune diseases on biosensor surfaces. For example, the biomarker tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine is presented and the kinetics of binding to a single-molecule nanoparticle optical biosensor (SMOBS) is analyzed.

Physiological Cellular Reactions Detection on Biosensor Surfaces

The detection of analytes involved in physiological cellular reactions is an important area of investigation of biosensor applications. This chapter analyzes examples of physiological cellular reaction detection on biosensor surfaces and discusses their kinetics. Fractal analysis is used to analyze the binding and dissociation (if applicable) kinetics for the binding and dissociation of different concentrations of bradykinin to a bradykinin B2 receptor on a RWG biosensor, the binding and dissociation of mβCD cholesterol to HeLa cells cultivated on a gold-plated prism, and the binding and dissociation (if applicable) of calcium + FRET-based calcium biosensor employing troponin for the binding and dissociation of TXNL in solution to the sensor-chip surface. Both single- and dual-fractal analyses have been used in the analysis. The dual-fractal analysis was used only when the single-fractal analyses did not provide an adequate fit. The fractal dimension provides a quantitative measure of the degree of heterogeneity present on the biosensor chip surface. The fractal dimension for the binding and dissociation phase, D f and D fd , respectively, is not a typical independent variable, such as analyte concentration, that can be directly manipulated. An increase in the fractal dimension value or the degree of heterogeneity on the biosensor surface leads, in general, to an increase in the binding rate coefficient. More such studies are required to determine whether the binding and dissociation rate coefficient(s), and subsequently the affinity values are sensitive to their fractal dimensions present on the biosensor surface with regard to these types of reactions.

Physiological Cellular Reactions Detection on Biosensor Surfaces: A Fractal Analysis

The detection of analytes involved in physiological cellular reactions is an important area of investigation of biosensor applications. This chapter analyzes examples of physiological cellular reaction detection on biosensor surfaces and discusses their kinetics. Fractal analysis is used to analyze the binding and dissociation (if applicable) kinetics for the binding and dissociation of different concentrations of bradykinin to a bradykinin B2 receptor on a RWG biosensor, the binding and dissociation of mβCD cholesterol to HeLa cells cultivated on a gold-plated prism, and the binding and dissociation (if applicable) of calcium + FRET-based calcium biosensor employing troponin for the binding and dissociation of TXNL in solution to the sensor-chip surface. Both single- and dual-fractal analyses have been used in the analysis. The dual-fractal analysis was used only when the single-fractal analyses did not provide an adequate fit. The fractal dimension provides a quantitative measure of the degree of heterogeneity present on the biosensor chip surface. The fractal dimension for the binding and dissociation phase, D f and D fd , respectively, is not a typical independent variable, such as analyte concentration, that can be directly manipulated. An increase in the fractal dimension value or the degree of heterogeneity on the biosensor surface leads, in general, to an increase in the binding rate coefficient. More such studies are required to determine whether the binding and dissociation rate coefficient(s), and subsequently the affinity values are sensitive to their fractal dimensions present on the biosensor surface with regard to these types of reactions.

Fabrication of Biosensors

This chapter analyzes the different types of biosensor fabrication procedures that have recently appeared in the literature. Some of the biosensor fabrication presented include those for glucose (biosensor using a nanocomposite electrode, screen-printed water-based carbon-ink microband biosensor, immobilized enzyme biosensor, ZnO nanoparticle/glucose oxidase biosensor, osmium complex and glucose oxidase biosensor, microencapsulated enzyme in a hydrophobic synthetic latex film biosensor, platinum nanowire array biosensor. Other fabrication techniques for biosensor fabrication mentioned include MI (for a potentiometric protein biosensor, polymer microarray on a chip, inkjet printing technology for an optical fiber imaging sensor conducting polymer polyaniline (Pani)-based biosensors (using ITO, biosensor fabrication procedure based on processable polyaniline nanoparticles, biosensor fabrication based on screen printing technology (DNA chips with an electrical readout for the detection of viral DNA), microband glucose biosensor, disposable screen printed electrodes, biosensor based on charge transfer technique, biosensor fabrication based on nanowire NEA, fabrication of dip-strip test systems, recrystallization technologies to fabricate a silicon nanowire biosensor, and porous silicon-based biosensor. In the future, other biosensor fabrication procedures would be developed that would be more suitable for the detection of analytes in solution and in the gas phase, other than those that are mentioned in this chapter or those that have already appeared in the literature.

Chapter 15 – Fractal Analysis of the Binding and Dissociation Kinetics of Protein Biomarkers and Other Medically Oriented Analytes on Biosensor Surfaces

The detection of the biomarkers of different diseases is an important area of biosensor development. Biosensors have also been used to detect medically related analytes which, above a certain threshold level, indicate the early incidence or onset of certain diseases. This chapter provides examples of the detection of different protein biomarkers and other medically related analytes that indicate the incidence of different diseases and analyzes the kinetics of binding and dissociation (if applicable) of biomarkers in such biosensors through fractal analysis. Both single- and dual-fractal analyses are used to model the binding and the dissociation kinetics. The examples analyzed include the following: sensitive immunoassay of a biomarker tumor necrosis factor (TNF)-α based on poly(guanine)-functionalized silica nanoparticle label, development of a screen-printed cholesterol biosensor, a doubly amplified electrochemical assay for carcinoembryonic antigen (CEA), a cholesterol biosensor based on poly-(3-hexylthiophene) self-assembled monolayer using surface plasmon resonance technique, protein kinase assay using peptide-conjugated gold nanoparticles, aptamer evolution for assay-based diagnostics for thrombin in solution, detection of thrombin by an electrochemical aptamer-based assay coupled to magnetic beads, gold nanoparticles for quantification of prostate specific antigen (PSA) protein biomarker, label-free analysis of transcription factors using microcantilever arrays, carp vitellogenin, and point-of-care (POC) biosensor systems for cancer diagnostics/prognostics.

Chapter 12 – Binding and Dissociation Kinetics of Different Analytes on Novel Biosensing Surfaces: A Fractal Analysis

Novel biosensors are continuously being developed to detect different analytes. This chapter provides examples of the detection of different analytes on novel biosensing surfaces and uses the fractal analysis technique to analyze the binding and dissociation (if applicable) kinetics of these examples. Single- and dual-fractal analysis is used to discuss the binding and dissociation of IgG species to a porous SiO 2 interferometric biosensor coated with protein A; binding (hybridization) using differential surface plasmon resonance; binding of glucose to a One Touch II blood glucose meter and a surface-enhanced Raman scattering (SERS) sensor; binding of H9 avian virus to cadmium quantum dots; and the binding of sodium ions of Na 0.44_x MnO 2 to a selective sodium ion sensor. Other novel biosensing techniques that have recently appeared in the research literature include a novel platform for the oriented buildup of immunoglobulins on a gold surface for a surface plasmon resonance imaging microarray; affinity-based chromatographic assays for thrombin; a new platform technology for DNA extraction and fast detection of gram positive bacteria; and a highly selective electrogenerated chemiluminescence (ECL) biosensor for the detection of target single-strand DNA (ss-DNA) using hairpin DNA as the recognition element. The fractal analysis provides a quantitative measure of the degree of heterogeneity on the sensing surface and links this degree of heterogeneity on the sensing surface to the binding and the dissociation (if applicable) rate coefficients. The versatility of the fractal analysis is demonstrated by its successful application to the kinetics of different analyte/receptor systems occurring on the different biosensing systems.

Binding and Dissociation Kinetics During Hybridization on Biosensor Surfaces

Hybridization is an important area of investigation for biosensors. This chapter provides different examples where hybridization is involved in the binding and dissociation (if applicable) of different analytes on biosensor surfaces and a discussion of the use of fractal analysis to analyze the binding and dissociation (if applicable) kinetics of those examples. The examples analyzed include the following: locked nucleic acid–based biosensors for surface interaction studies and biosensor development, real-time monitoring of the activity and kinetics of T4 polynucleotide kinase (PNK) by a singly labeled DNA-hairpin smart probe coupled with l exonuclease cleavage, competitive kinetic model of nucleic acid surface hybridization in the presence of point mutants, enhancement of DNA immobilization and hybridization on gold electrode modified by nanogold electrodes, sequential injection analysis system for the sandwich hybridization-based detection of nucleic acids, a fluorescence-based array biosensor, electrochemical detection of 17-β estradiol using DNA aptamer immobilized gold electrode chip, surface plasmon resonance study of cooperative interactions of estrogen receptor α and transcriptional factor Sp1 with composite DNA elements, and ultrasensitive optical DNA biosensor based on surface immobilization of molecular beacon (MB) by a bridge structure. Advantages of the fractal analysis method is that the fractal dimension provides a quantitative measure of the degree of heterogeneity on the biosensor surface, and it helps link the degree of heterogeneity on the surface with the binding and the dissociation rate coefficients.

Binding of the Same Analyte to Different Biosensor Surfaces

An analyte may be detected by different biosensors. This chapter provides fractal analysis of examples from recent research literature wherein the same analyte has been detected by different biosensors. The goals of this analysis are to gain further physical insight into these systems and find why particular ranges of fractal dimensions (degree of heterogeneity) existed on the biosensor surface and in the binding rate coefficients. These physical insights could be of value for analyte-receptor systems, in general, but particularly so in those analyte-receptor systems that exhibit biomedical/medical applications such as glucose, thrombin, α-fetoprotein (AFP), and carcinogenic analytes or those analytes that may be used as cancer biomarkers.