New Perspectives in Biosensors Technology and Applications Part 12 pdf

New Perspectives in Biosensors Technology and Applications 322 + - C 2 V OUT + Comparator V OUT + V OUT - Φ 1d Ag/AgCl SnO 2 /ITO glass pH buffer solution + - + - C 1 V BIAS Φ 2 Φ 1 Φ 1 V ref+ V ref- V OUT + V OUT - EGFET-OP Fig. 15. Implementation of the pH-to-digital modulator The transfer function of the pH-to-digital converter can be derived as follows: 1 1 pH 1 2 1 2 C1z Y1 V E C C 11z C − − ⎛⎞ − = +⋅+ ⋅ ⎜⎟ ⎛⎞ ⎝⎠ +− ⎜⎟ ⎝⎠ (12) where Y denotes the average digital output of the quantizer, and E indicates the quantization noise. When choosing C 1 =C 2 , the expression will be simplified to: 1 pH Y2V (1z)E − = ⋅+−⋅ (13) Furthermore, the quantization noise is first-order shaped as expected. Through an on-chip simple digital filter realized by 14-bits up-down counter, the digital average value of the comparator was obtained after shifting the bits of the output code depending on the sampled numbers. The high frequency quantization noise was filtered out. The general regenerative latch comparator shown in Fig. 12 was employed as the quantizer in the delta- sigma modulator. The direct pH-to-digital converter derived is used to measure the pH response. The chip has been encapsulated in a standard dual inline package. The sensing art has been exposed to test solutions in the ion concentration range between pH 2 and 12. The measurements were performed under a 1.8V power supply, and the sampling frequency of the converter was 6.25 MHz. Through an on-chip simple digital filter realized by 14-bits up-down counter, the digital average value of the comparator was obtained after shifting the bits of the output code depending on the sampled numbers. Layout microphotograph of the pH-to-digital converter circuit is shown in Fig. 16. The circuit (without pad) occupied an area of 0.66mm × 0.43mm. The input range of the delta-sigma modulator is 1.2V since the positive and negative reference voltages of the delta-sigma modulator are 0.3V and 1.5V, respectively. The sensitivity of the pH-to-digital converter is 197 digital counts/pH. The plot of the digital output versus pH value is shown in Fig. 17. Deviation between measured points and the linear regression line of sensitivity shown in Fig. 18 is under ±0.02pH. The performance of this pH-to-digital converter was summarized in Table 1. CMOS, Delta-Sigma pH-to-Digital Converter as New Integrated Device for Potentiometric Biosensors Applications 323 Digital control circuits Delta-sigma pH-to-digital modulator circuits Fig. 16. Layout microphotograph of the pH-to-digital converter circuit 24681012 2500 3000 3500 4000 4500 Digital Output Response Approx. Sensitivity : 197counts/pH Digital Output (counts) pH Value (pH) Fig. 17. Plot of the digital output versus pH value New Perspectives in Biosensors Technology and Applications 324 2 4 6 8 10 12 -0.005 0.000 0.005 0.010 0.015 0.020 pH Error (pH) pH Value (pH) pH Error Fig. 18. pH error of the proposed pH-to-digital converter Parameter pH-to-Digital Converter Supply Voltage 1.8V Power Consumption 9.8mW Dynamic Range pH2 - pH12 Sensitivity 197 digital counts/pH Gain Error 2% pH Error ±0.02pH Sampling Frequency 6.25MHz Table 1. Performance summary 3. Conclusion A CMOS ΣΔ pH-to-digital converter has been developed for continuous monitoring of H + - ion concentrations in this research. The ΣΔ pH-to-digital converter, constructed using EGFET-OP to realize switched-capacitor (SC) ΣΔ converter, converted directly the H + -ion concentration into digital form. First order low pass ΣΔ modulator constructed using EGFET-OP was used to transfer the signal into digital. Through an on-chip simple digital filter realized by 14-bits up-down counter, the digital average value of the comparator was obtained after shifting the bits of the output code depending on the sampled numbers. The high frequency quantization noise was filtered out. The circuit (without pad) occupied an area of 0.66mm × 0.43mm. The sensitivity of the pH-to-digital converter is about 197 digital counts/pH. This chip, fabricated in a 0.18-um CMOS 1P6M process, operated at a 1.8V supply voltage and normal sampling rate of 6.25MHz. The linearity errors of the converter in the H + -ion concentration range between pH 2 and pH 10 is less than 2%, and the minimum detectable pH value can reach as small as ±0.02pH. CMOS, Delta-Sigma pH-to-Digital Converter as New Integrated Device for Potentiometric Biosensors Applications 325 4. Acknowledgment The authors would like to thank the Sitronix Technology and Chip Implementation Center (CIC) of the National Science Council, Taiwan, for fabricating the chips. 5. References Bergveld, P. (1970). Development of an Ion-Sensitive Solid-State Device for Neurophysiological Measurements. IEEE Transactions on Biomedical Engineering, Vol. 17, No. 1, (January 1970), pp. 70-71, ISSN 0018-9294 Yin, L. T.; Chou, J. C.; Chung, W. Y.; Sun, T. P., & Hsing, S. K. (2000). Separate Structure Extended Gate H + -Ion Sensitive Field Effect Transistor on a Glass Substrate. Sensors and Actuators B, Vol. 71, (November 2000), pp. 106-111, ISSN 0925-4005 Chan, P. K. & Chen, D. Y. (2007). A CMOS ISFET Interface Circuit with Dynamic Current Temperature Compensation Technique. IEEE Transactions on Circuits System I, Vol. 54, (January 2007), pp. 119-129, ISSN 1057-7122 Kuo, C. H.; Wu, Chen, S. L.; Ho, L. A., & Liu, S. I. (2001). CMOS Oversampling Magnetic to Digital Converters. IEEE Journal of Solid-State Circuits, Vol. 36, (October 2001), pp. 1582-1586, ISSN 0018-9200 Lemkin, M. & Boser, B. E. (1999). A Three-Axis Micromachined Accelerometer with a CMOS Position-Sense Interface and Digital Offset-Trim Electronics. IEEE Journal of Solid- State Circuits, Vol. 34, (April 1999), pp. 456-468, ISSN 0018-9200 Petkov, V. P. & Boser, B. E. (2005). A Fourth-Order ΣΔ Interface for Micromachined Inertial Sensors. IEEE Journal of Solid-State Circuits, Vol. 40, (August 2005), pp. 1602-1609, ISSN 0018-9200 Spiegel, J. V. D.; Lauks, I.; Chan, P., & Babic D. (1983). The Extended Gate Chemical Sensitive Field Effect Transistor as Multi-Species Microprobe. Sensors and Actuators, Vol. 4, (October 1983), pp. 291-298, ISSN 0250-6874 Chin, Y. L.; Chou, J. C.; Chung, W. Y.; Sun, T. P., & Hsing, S. K. (2001). A Novel SnO 2 /Al Discrete Gate ISFET pH Sensor with CMOS Standard Process. Sensors and Actuators B , Vol. 75, (April 2001), pp. 36-42, ISSN 0925-4005 Chou, J. C. & Chen, C. W. (2009). Fabrication and Application of Ruthenium-Doped Titanium Dioxide Films as Electrode Material for Ion-Sensitive Extended-Gate FETs. IEEE Sensor Journal, Vol. 9, (April 2009), pp. 277-284, ISSN 1530-437X Grattarola, M.; Massobrio, G., & Matinoia S. (1992). Modeling H+-Sensitive FET’s with SPICE. IEEE Transactions on Electron Devices, Vol. 39, (April 1992), pp. 813-819, ISSN 0018-9383 Fung, C. D.; Cheung, P. W., & Ko, W. H. (1986). A Generalized Theory of an Electrolyte- Insulator-Semiconductor Field-Effect Transistor. IEEE Transactions on Electron Devices, Vol. 33, (January 1986), pp. 8-18, ISSN 0018-9383 Van Hal, R. E. G.; Eijkel, J. C. T., & Bergveld, P. (1995). A Novel Description of ISFET Sensitivity with the Buffer Capacity and Double-Layer Capacitance as Key Parameters. Sensors and Actuators B, Vol. 24, (March 1995), pp. 201-205, ISSN 0925- 4005 Pezekwe, C. D. & Boser, B. E. (2008). A Mode-Matching ΣΔ Closed-Loop Vibratory Gyroscope Readout Interface with a 0.004°/s/ √Hz Noise Floor over a 50 Hz Band. IEEE Journal of Solid-State Circuits , Vol. 43, (December 2008), pp. 3039-3048, ISSN 0018- 9200 New Perspectives in Biosensors Technology and Applications 326 Boser, B. & Wooley, B. (1988). The Design of ΣΔ Modulation Analog-to-Digital Converters. IEEE Journal of Solid-State Circuits, Vol. 23, (December 1988), pp. 1298-1308, ISSN 0018-9200 Norsworthy, Ed. S.; Schreier, R., & Temes, G. (1997). Delta-Sigma Data Converters: Theory, Design, and Simulation , IEEE Press, ISBN 0780310454, New York Johns, D., & Martin, K. (1997). Analog Integrated Circuit Design, Wiley, ISBN 0471144487, Cloth Part 2 Biosensors for Health 16 Design and Preparation of Nanostructured Prussian Blue Modified Electrode for Glucose Detection Wanqin Jin, Zhenyu Chu and Yannan Zhang State key laboratory of Materials-Oriented Chemical Engineering, Nanjing University of Technology China 1. Introduction High sensitivity and anti-interference ability are critical parameters in glucose biosensor design, because of the complexity of blood composition. Prussian blue (PB) is a hexacyanoferrate with two different iron valences (+2 and +3) and was initially developed as a blue pigment in the 1700s (Bartoll, 2008). Recently researchers found that PB is an excellent material for use in the fabrication of glucose biosensors, because of its non-toxicity, high electrocatalytic activity, and low overpotential detection (Ricci & Palleschi, 2005; Karyakin et al., 2007; Wang, 2008). During glucose detection, hydrogen peroxide (H 2 O 2 ) is produced via the enzymatic oxidation of glucose. Subsequently, PB reduces the H 2 O 2 and transfers the electrons to generate a current response on the electrode surface. Thus, PB is the mediator of electron transfer in the detection process, making the electron sensitivity of PB - a key component of biosensor performance. Chemical deposition and electrodeposition are the main processes used to synthesize a PB film on the electrode surface (Itaya et al., 1982; Zakharchuket al., 1995). However, the sensitivity of the electrode modified with a PB film cannot be controlled, because of difficulties in film construction. Millward et al. (2001) used a self-assembly approach to deposit a PB film on a gold electrode, which greatly accelerated the development of PB- based biosensors. The advantages of applying nanostructured materials for improving biosensor performance have been recognized in recent years, especially for improving sensitivity (Cella et al., 2010; Cao et al., 2010). The utilization of nanoparticles can enhance electrode performance, even if the same materials are used. We developed a PB nanostructure to produce a high sensitivity biosensor for glucose detection, which can be directly grown on the electrode surface. We previously synthesized PB nanoparticles on a platinum (Pt) electrode surface using a self-assembly approach (Liu et al., 2009). We found that the size and quantity of PB particles greatly affected H 2 O 2 detection performance. After immobilization of the glucose enzyme, this type of biosensor was sensitive to trace concentrations of glucose in solution (Liu et al. 2009). However, it was difficult to form a regularly structured PB particle film, when synthesis was conducted via self-assembly. Thus, we further developed the self-assembly approach to deliver a novel method for obtaining a regular film of PB crystals, are thereby improving biosensor sensitivity and effectiveness. New Perspectives in Biosensors Technology and Applications 330 2. Mechanism of H 2 O 2 detection PB is typically produced from a reaction between two compounds, K 4 [Fe(CN) 6 ] and FeCl 3 (see equation 1). 4 46 3 63 463 6 3[( )]4 [( )] 12 [( )] [( )]3 KFeCN FeCl FeFeCN KCl K Fe CN FeCl KFe Fe CN KCl +→ + +→ + (1) KFe[Fe(CN) 6 ] and Fe 4 [Fe(CN) 6 ] 3 are soluble and insoluble PB, respectively, and both species are required. The unit cell of PB is a face-centered cubic structure with lattice parameters, a = b = c = 10.143 Å. It is interesting that neighboring iron ions have different valences. The Fe 2+ ion, in the Fe(CN) 6 4+ complex, is readily reduced to the Fe 3+ ion. The signal generated by electron transfer from Fe(CN) 6 4+ is generally used in electrochemical detection to characterize the properties of the PB film. Fig. 1. (a) The structure of the PB unit cell. (b) Mechanism of H 2 O 2 detection. PB has two functions when used as a material in biosensor fabrication, i.e., electrocatalysis and electron transfer: When a potential (typically - 0.05 V) is imposed on a PB modified electrode, the PB will acquire electrons and move into its reduced state, Prussian White (PW). If H 2 O 2 is present in the detection system, PW rapidly reduces H 2 O 2 to OH – . After donating electrons, PW reverts back to PB (Fig. 1). The direction of electron transfer during this process is from the electrode surface to H 2 O 2 . Thus, electrocatalysis and electron transfer determine overall electrode performance. Regular crystalline structure is a morphological feature that has been widely demonstrated to enhance catalytic ability (Liu et al., 2010; Prevot et al., 2011). However, it is difficult to control regular PB crystal growth using conventional preparative methods, because of its rapid reaction rate during crystal formation. Consequently, novel methods are required to facilitate the regular crystal structure growth in the PB film. 3. PB crystal formation using a self-assembly approach Self-assembly is a common approach for production of PB-modified electrodes. Scheme 1 shows the process of PB synthesis, which starts with a pre-coating layer of polyelectrolyte, to provide electrostatic adsorption sites, followed by dipping the electrode into a reactive solution for PB formation. Poly(diallyldimethylammonium chloride) (PDDA) is typically [...]... aggregation of nanoparticles has been 344 New Perspectives in Biosensors Technology and Applications found in the presence of nitrotyrosine The interactions of nitrotyrosine with gold nanoparticles and two fluorescent dyes with different spectral characteristics have also been investigated These interactions result in changes in the resonance elastic light scattering (RELS) and fluorescence quenching that can... (glycine –COOH), pK3 = 8.72 (–SH group), pK4 = 9.49 (–NH2 group) The enhancement of RELS from AuNP5nm by GSH molecules is attributed to the size increase of AuNP due to the ligand exchange (i.e replacing short-chain citrate molecules in the nanoparticle shell with longer-chain GSH molecules) and interparticle interactions leading to AuNP assembly 350 New Perspectives in Biosensors Technology and Applications. .. the biomarker-induced AuNP assembly and corroborate the RELS measurements and HR-TEM imaging The results of molecular dynamics and quantum mechanical calculations support the mechanism of the formation of GSH- and Hcys-linkages in the interparticle interactions and show that multiple H-bonding can occur In contrast to homocysteine and glutathione that induce gold nanoparticle assembly in specific pH... While in the Hcys-induced assembly, the main forces are Hbonding, in the case of GSH-induced assembly, the zwitterionic forces are dominant, although the H-bonding plays also a role (Lim et al., 2007, Lim et al., 2008) No aggregation of nanoparticles has been found in the presence of nitrotyrosine Taking into account the decrease in particle concentration due to assembly and assuming λ = const, the increase... main redox regulation system in living organism's homeostasis GSH protects cells against organic peroxides and damaging radicals, and is involved in signaling processes associated with cell apoptosis The diminished active GSH levels in cells and body fluids lead to the reduced antioxidation capacity (Noble et al., 2005) to protecting against radicals and have been found to increase susceptibility to... is now mounting evidence that oxidative and nitrosative stress resulting from hyperglycemia is involved in the development of diabetes and is implicated in the micro- and macrovascular complications of the disease Such biomarkers of oxidative stress as nitrotyrosine and homocysteine show elevated levels and glutathione shows a decreased level in a progressing disease In this study, the interactions... identified, including glutathione (GSH), 3-nitrotyrosine (NT), homocysteine (Hcys), and cysteine (Cys) The tripeptide glutathione and its oxidized form, glutathione disulphide (GSSG), form a redox potential maintenance system in all eukaryotic cells Since glutathione efficiently protects the DNA, proteins and lipid membranes from radical attacks, its diminished level is signaling an oxidative stress and the increased... homocysteine have been investigated using resonance elastic light scattering (RELS) and plasmonic UV-Vis spectroscopy The high sensitivity of the RELS measurements enables monitoring of ligand exchanges and the biomarker-induced AuNP assembly The viability of designing simple and rapid assays for the detection of glutathione and homocysteine is discussed The surface plasmon band broadening and bathochromic... the ligand exchange process has completed and nanoparticle shells are saturated with Hcys At neutral solutions, Hcys-capped AuNP do not assemble In the following, we present a method for Hcys-capped AuNP assembly by interparticle crosslinking using glutaraldehyde as the linker (Scheme 1b) The linking is achieved through the condensation reaction between aldehyde groups of glutaraldehyde and amine groups... biomarker-induced assembly of monolayer-protected gold nanoparticles is evaluated in view of prospective applications of gold nanoparticles in designing inexpensive nanostructured sensors and microsensor arrays for field-deployable and pointof-care utilization 2 Redox-potential homeostasis and protection against oxidative-stress Glutathione and its oxidized disulfide form (GSSG) constitute the main redox . Wanqin Jin, Zhenyu Chu and Yannan Zhang State key laboratory of Materials-Oriented Chemical Engineering, Nanjing University of Technology China 1. Introduction High sensitivity and anti-interference. novel method for obtaining a regular film of PB crystals, are thereby improving biosensor sensitivity and effectiveness. New Perspectives in Biosensors Technology and Applications 330. prompted the investigation of surface coverage. The fractional electrode coverage rate (θ) of PDDA was estimated according to equation 2. New Perspectives in Biosensors Technology and Applications