Label-free detection of DNA hybridization using a porous poly-Si ion-sensitive field effect transistor

We report an ultra-sensitive, label-free detection system for DNA hybridization using a porous poly-Si gate ion-sensitive field effect transistor. Various physical and chemical characteristics of the sensor system were optimized, along with parameters affecting the immobilization of a label-free single-strand DNA and the specific hybridization of a complementary sequence on the silicon oxide layer, for quantitative detection down to the femtomole level. X-ray photoelectron spectroscopy (XPS) was employed to investigate the nature of the modifications to the porous layer by covalent bonding. Due to the utilization of nanoscopic pores at the gate region, the Debye screening length is no longer a limitation for macromolecule detection. In addition to its compatibility with the CMOS fabrication process, this sensor is a promising device for the label-free electrical detection of DNA pairs or other biomolecules at low concentrations.

[1]  Euisik Yoon,et al.  Label-Free CMOS Bio Sensor With On-Chip Noise Reduction Scheme for Real-Time Quantitative Monitoring of Biomolecules , 2012, IEEE Transactions on Biomedical Circuits and Systems.

[2]  P. Bergveld.  The impact of MOSFET-based sensors , 1985 .

[3]  Shams Mohajerzadeh,et al.  High-Sensitivity Ion-Selective Field-Effect Transistors Using Nanoporous Silicon , 2010, IEEE Electron Device Letters.

[4]  You-Lin Wu,et al.  Highly sensitive polysilicon wire sensor for DNA detection using silica nanoparticles/γ-APTES nanocomposite for surface modification , 2011 .

[5]  J. Janata,et al.  Field effect transistor sensitive to penicillin , 1980 .

[6]  Markus Fischer,et al.  Field effect of screened charges: electrical detection of peptides and proteins by a thin-film resistor. , 2006, Chemphyschem : a European journal of chemical physics and physical chemistry.

[7]  Ronald W. Davis,et al.  Direct electrical detection of DNA synthesis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Jang-Kyoo Shin,et al.  Detection of DNA and Protein Molecules Using an FET‐Type Biosensor with Gold as a Gate Metal , 2004 .

[9]  J. Sipe,et al.  Nanoscale porous silicon waveguide for label-free DNA sensing. , 2008, Biosensors & bioelectronics.

[10]  O. Larsson,et al.  Silanized nucleic acids: a general platform for DNA immobilization. , 2000, Nucleic acids research.

[11]  P. Estrela,et al.  Field effect detection of biomolecular interactions , 2005 .

[12]  Xuema Li,et al.  Sequence-Specific Label-Free DNA Sensors Based on Silicon Nanowires , 2004 .

[13]  Gilles Horowitz,et al.  Advances in organic transistor-based biosensors: from organic electrochemical transistors to electrolyte-gated organic field-effect transistors , 2012, Analytical and Bioanalytical Chemistry.

[14]  Yuji Miyahara,et al.  DNA sequencing based on intrinsic molecular charges. , 2006, Angewandte Chemie.

[15]  G. Slater,et al.  Effective Debye length in closed nanoscopic systems: A competition between two length scales , 2006, Electrophoresis.

[16]  Y. Lyubchenko,et al.  Atomic force microscopy imaging of DNA covalently immobilized on a functionalized mica substrate. , 1999, Biophysical journal.

[17]  Hiroyuki Fujita,et al.  CMOS-compatible fabrication of top-gated field-effect transistor silicon nanowire-based biosensors , 2011 .

[18]  A. Steel,et al.  Immobilization of nucleic acids at solid surfaces: effect of oligonucleotide length on layer assembly. , 2000, Biophysical journal.

[19]  Michael J. Schöning,et al.  Bio FEDs (Field‐Effect Devices): State‐of‐the‐Art and New Directions , 2006 .

[20]  Y. Miyahara,et al.  Label-Free Detection of DNA by Field-Effect Devices , 2011, IEEE Sensors Journal.

[21]  J. W. Schultze,et al.  Capacitive microsensors for biochemical sensing based on porous silicon technology , 2000 .

[22]  Ping Gong,et al.  Surface coverage and structure of mixed DNA/alkylthiol monolayers on gold: characterization by XPS, NEXAFS, and fluorescence intensity measurements. , 2006, Analytical chemistry.

[23]  Peter Kordos,et al.  Biochemical sensors with structured and porous silicon capacitors , 2000 .

[24]  Nicolas H Voelcker,et al.  Porous silicon biosensors on the advance. , 2009, Trends in biotechnology.

[25]  Eric Stern,et al.  Determination of molecular configuration by debye length modulation. , 2011, Journal of the American Chemical Society.

[26]  Y Husimi,et al.  Real-time monitoring of DNA polymerase reactions by a micro ISFET pH sensor. , 1992, Analytical chemistry.

[27]  V. Subramanian,et al.  DNA hybridization detection with organic thin film transistors: toward fast and disposable DNA microarray chips. , 2007, Biosensors & bioelectronics.

[28]  Fred J Sigworth,et al.  Importance of the Debye screening length on nanowire field effect transistor sensors. , 2007, Nano letters.

[29]  P. Sorger,et al.  Electronic detection of DNA by its intrinsic molecular charge , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Jan Linnros,et al.  Silicon nanoribbons for electrical detection of biomolecules. , 2008, Nano letters.

[31]  J. Tamaoka,et al.  Improved immobilization of DNA to microwell plates for DNA-DNA hybridization. , 1996, Nucleic acids research.

[32]  J. E. Olsen,et al.  DNA-DNA hybridization determined in micro-wells using covalent attachment of DNA. , 2000, International journal of systematic and evolutionary microbiology.

[33]  Charles M. Lieber,et al.  Nanowire-based biosensors. , 2006, Analytical chemistry.

[34]  Hiroshi Kawarada,et al.  Label-free DNA sensors using ultrasensitive diamond field-effect transistors in solution. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[35]  O. Akhavan,et al.  Toward single-DNA electrochemical biosensing by graphene nanowalls. , 2012, ACS nano.

[36]  David R. S. Cumming,et al.  Encapsulation of a liquid-sensing microchip using SU-8 photoresist , 2004 .

[37]  L. Raffo,et al.  A CMOS, fully integrated sensor for electronic detection of DNA hybridization , 2006, IEEE Electron Device Letters.

[38]  Jürgen Popp,et al.  UV cross-linking of unmodified DNA on glass surfaces , 2009, Analytical and bioanalytical chemistry.

[39]  R. Thewes,et al.  A Fully Electronic Label-Free DNA Sensor Chip , 2007, IEEE Sensors Journal.

[40]  Chih-Heng Lin,et al.  Ultrasensitive and label-free detection of pathogenic avian influenza DNA by using CMOS impedimetric sensors. , 2012, Biosensors & bioelectronics.

[41]  R. Thewes,et al.  A fully electronic DNA sensor with 128 positions and in-pixel A/D conversion , 2004, IEEE Journal of Solid-State Circuits.

[42]  Gyu-Hyeong Cho,et al.  A CMOS label-free DNA sensor using electrostatic induction of molecular charges. , 2012, Biosensors & bioelectronics.

[43]  Dmitriy A. Khodakov,et al.  Molecular Structure of 3-Aminopropyltriethoxysilane Layers Formed on Silanol-Terminated Silicon Surfaces , 2012 .

[44]  Ying-Chih Chang,et al.  Label-free dual sensing of DNA molecules using GaN nanowires. , 2009, Analytical chemistry.

[45]  F. Pouthas,et al.  DNA detection on transistor arrays following mutation-specific enzymatic amplification , 2004 .

[46]  D. Porath,et al.  The effect of the number of parallel DNA molecules on electric charge transport through ‘standing DNA’ , 2007, Nanotechnology.

[47]  Rashid Bashir,et al.  Electrical characterization of DNA molecules in solution using impedance measurements , 2008 .

[48]  Bernard P. Puc,et al.  An integrated semiconductor device enabling non-optical genome sequencing , 2011, Nature.

[49]  N Balasubramanian,et al.  DNA sensing by silicon nanowire: charge layer distance dependence. , 2008, Nano letters.

[50]  Guo-Jun Zhang,et al.  Morpholino-functionalized silicon nanowire biosensor for sequence-specific label-free detection of DNA. , 2010, Biosensors & bioelectronics.

[51]  Zhaohui Zhong,et al.  Detection beyond the Debye screening length in a high-frequency nanoelectronic biosensor. , 2012, Nano letters.

[52]  John Alderman,et al.  A DNA diagnostic biosensor: development, characterisation and performance , 2000 .

[53]  E Souteyrand,et al.  Assessment of porous silicon substrate for well-characterised sensitive DNA chip implement. , 2005, Biosensors & bioelectronics.

[54]  Andreas Offenhäusser,et al.  Detection of DNA hybridization by a field‐effect transistor with covalently attached catcher molecules , 2006 .

[55]  J. N. Russell,et al.  Interfacial electrical properties of DNA-modified diamond thin films: intrinsic response and hybridization-induced field effects. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[56]  Multiplexed SOI BioFETs. , 2011, Biosensors & bioelectronics.

[57]  Thomas Haneder,et al.  A digital CMOS DNA chip , 2005, 2005 IEEE International Symposium on Circuits and Systems.

[58]  Luisa Torsi,et al.  Microcantilevers and organic transistors: two promising classes of label-free biosensing devices which can be integrated in electronic circuits , 2011, Analytical and Bioanalytical Chemistry.

[59]  E. Alocilja,et al.  Characterization of Nanoporous Silicon-Based DNA Biosensor for the Detection of Salmonella Enteritidis , 2008, IEEE Sensors Journal.

[60]  Martin Dufva,et al.  An inexpensive and simple method for thermally stable immobilization of DNA on an unmodified glass surface: UV linking of poly(T)10-poly(C)10-tagged DNA probes. , 2008, BioTechniques.

[61]  Andreas Offenhäusser,et al.  Possibilities and limitations of label-free detection of DNA hybridization with field-effect-based devices , 2005 .

[62]  F. Uslu,et al.  Labelfree fully electronic nucleic acid detection system based on a field-effect transistor device. , 2004, Biosensors & bioelectronics.

[63]  T. G. Drummond,et al.  Electrochemical DNA sensors , 2003, Nature Biotechnology.

[64]  R. Lathe,et al.  Hybridization parameters revisited: solutions containing SDS. , 2002, BioTechniques.

[65]  L. Benini,et al.  Microelectrodes on a Silicon Chip for Label-Free Capacitive DNA Sensing , 2006, IEEE Sensors Journal.

[66]  Massimo Barbaro,et al.  Label-free, direct DNA detection by means of a standard CMOS electronic chip , 2012 .

[67]  Lidan You,et al.  Effect of nanowire number, diameter, and doping density on nano-FET biosensor sensitivity. , 2011, ACS nano.

[68]  R. Cobbold,et al.  Analysis of the threshold voltage and its temperature dependence in electrolyte-insulator-semiconductor field-effect transistors (EISFET's) , 1987, IEEE Transactions on Electron Devices.

[69]  Pengfei Dai,et al.  Silicon-nanowire-based CMOS-compatible field-effect transistor nanosensors for ultrasensitive electrical detection of nucleic acids. , 2011, Nano letters.

[70]  Junghuei Chen,et al.  Covalent attachment of shape-restricted DNA molecules on amine-functionalized Si(1 1 1) surface , 2009 .

[71]  Lloyd M. Smith,et al.  DNA Attachment and Hybridization at the Silicon (100) Surface , 2002 .

[72]  Xin Sheng Zhao,et al.  Monitoring DNA hybridization on alkyl modified silicon surface through capacitance measurement. , 2003, Biosensors & bioelectronics.

[73]  James R Heath,et al.  Quantitative real-time measurements of DNA hybridization with alkylated nonoxidized silicon nanowires in electrolyte solution. , 2006, Journal of the American Chemical Society.

[74]  E. Souteyrand,et al.  DIRECT DETECTION OF THE HYBRIDIZATION OF SYNTHETIC HOMO-OLIGOMER DNA SEQUENCES BY FIELD EFFECT , 1997 .

[75]  Mark A. Reed,et al.  Label-free immunodetection with CMOS-compatible semiconducting nanowires , 2007, Nature.