5×5 CMOS capacitive sensor array for detection of the neurotransmitter dopamine.

This work presents miniaturized CMOS (complementary metal oxide semiconductor) capacitive sensors for detection of the neurotransmitter dopamine (DA) down to the sub-fM range. Sensing resolution is significantly enhanced by monolithic sensor integration to reduce the parasitic effect and the use of sub-μm interdigitated microelectrodes as the sensing interface. The 5 × 5 sensor array contains five designs of different electrode sizes and each design has five sensors. The positive charges produced from protonation of boronate and amino group after immobilization of 4-carboxyphenylboronic acid (CPBA) result in an increase of the electrode-analyte capacitance. Then the negative charges produced after binding of CPBA and DA molecules decrease the electrode-analyte capacitance. Signal transduction is achieved through a CMOS readout circuit whose output frequency is inversely proportional to the capacitance. Experimental results showed the ratios of average percentage capacitance changes of the experiment groups over those of the control groups were all larger than one for the five designs at DA concentration of 0.1 fM. Selectivity against the non-analyte species, such as tyramine, has also been demonstrated.

[1]  Allen J. Bard,et al.  Electrochemical Methods: Fundamentals and Applications , 1980 .

[2]  Bo Mattiasson,et al.  Continuous measurements of a binding reaction using a capacitive biosensor. , 2005, Biosensors & bioelectronics.

[3]  S. Sherman,et al.  Single-chip surface micromachined integrated gyroscope with 50°/h Allan deviation , 2002, IEEE J. Solid State Circuits.

[4]  A. Bard Electrochemical methods : fundamentals and applictions / Allen J. Bard, Larry R. Faulkner , 1980 .

[5]  S. Yao,et al.  Kinetics of DNA binding with chloroquine phosphate using capacitive sensing method. , 2003, Biosensors & bioelectronics.

[6]  E. Stigter,et al.  An improved coating for the isolation and quantitation of interferon-gamma in spiked plasma using surface plasmon resonance (SPR). , 2005, Biosensors & bioelectronics.

[7]  Booncharoen Wongkittisuksa,et al.  Label-free capacitive immunosensor for microcystin-LR using self-assembled thiourea monolayer incorporated with Ag nanoparticles on gold electrode. , 2008, Biosensors & bioelectronics.

[8]  Raj Mutharasan,et al.  Near real-time detection of Cryptosporidium parvum oocyst by IgM-functionalized piezoelectric-excited millimeter-sized cantilever biosensor. , 2008, Biosensors & bioelectronics.

[9]  Nader Pourmand,et al.  Giant magnetoresistive biochip for DNA detection and HPV genotyping. , 2008, Biosensors & bioelectronics.

[10]  Hsieh-Cheng Han,et al.  Application of parylene-coated quartz crystal microbalance for on-line real-time detection of microbial populations. , 2009, Biosensors & bioelectronics.

[11]  Booncharoen Wongkittisuksa,et al.  Capacitive biosensor for quantification of trace amounts of DNA. , 2009, Biosensors & bioelectronics.

[12]  J V Yakhmi,et al.  Time response and stability of porous silicon capacitive immunosensors. , 2007, Biosensors & bioelectronics.

[13]  Aviad Hai,et al.  Acetylcholinesterase-ISFET based system for the detection of acetylcholine and acetylcholinesterase inhibitors. , 2006, Biosensors & bioelectronics.

[14]  Andreas Hierlemann,et al.  Impedance characterization and modeling of electrodes for biomedical applications , 2005, IEEE Transactions on Biomedical Engineering.

[15]  Qing Bai,et al.  Single-unit neural recording with active microelectrode arrays , 2001, IEEE Transactions on Biomedical Engineering.

[16]  Hai-Feng Ji,et al.  Organophosphorus hydrolase multilayer modified microcantilevers for organophosphorus detection. , 2007, Biosensors & bioelectronics.

[17]  J. Mitchell,et al.  Ultrasensitive detection of testosterone using conjugate linker technology in a nanoparticle-enhanced surface plasmon resonance biosensor. , 2009, Biosensors & bioelectronics.

[18]  L. Benini,et al.  CMOS DNA Sensor Array With Integrated A/D Conversion Based on Label-Free Capacitance Measurement , 2006, IEEE Journal of Solid-State Circuits.

[19]  Ivar Giaever,et al.  A morphological biosensor for mammalian cells , 1993, Nature.

[20]  N. Miura,et al.  Surface plasmon resonance biosensor for dopamine using D3 dopamine receptor as a biorecognition molecule. , 2007, Biosensors & bioelectronics.

[21]  Yong-Sang Kim,et al.  Development of a microfabricated disposable microchip with a capillary electrophoresis and integrated three-electrode electrochemical detection. , 2005, Biosensors & bioelectronics.

[22]  Wen-Li Jia,et al.  Highly selective and sensitive determination of dopamine using a Nafion/carbon nanotubes coated poly(3-methylthiophene) modified electrode. , 2006, Biosensors & bioelectronics.

[23]  Yang Xiang,et al.  Aptamer-based piezoelectric quartz crystal microbalance biosensor array for the quantification of IgE. , 2009, Biosensors & bioelectronics.

[24]  S Arana,et al.  Magnetoresistive immunosensor for the detection of Escherichia coli O157:H7 including a microfluidic network. , 2009, Biosensors & bioelectronics.

[25]  J-P Raskin,et al.  Electrical detection of DNA hybridization: three extraction techniques based on interdigitated Al/Al2O3 capacitors. , 2007, Biosensors & bioelectronics.

[26]  V Chu,et al.  Detection of DNA and proteins using amorphous silicon ion-sensitive thin-film field effect transistors. , 2008, Biosensors & bioelectronics.

[27]  Shusheng Zhang,et al.  Dendrimers-based DNA biosensors for highly sensitive electrochemical detection of DNA hybridization using reporter probe DNA modified with Au nanoparticles. , 2009, Biosensors & bioelectronics.

[28]  Yanbin Li,et al.  Interdigitated Array microelectrode-based electrochemical impedance immunosensor for detection of Escherichia coli O157:H7. , 2004, Analytical chemistry.

[29]  Bo Mattiasson,et al.  A comparative study of capacitive immunosensors based on self-assembled monolayers formed from thiourea, thioctic acid, and 3-mercaptopropionic acid. , 2006, Biosensors & bioelectronics.