Development of Si-based electrical biosensors: Simulations and first experimental results (original) (raw)
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Direct electrical detection of hybridization at DNA-modified silicon surfaces
Biosensors and Bioelectronics, 2004
Electrochemical impedance spectroscopy was used to investigate the changes in interfacial electrical properties that arise when DNA-modified Si(1 1 1) surfaces are exposed to solution-phase DNA oligonucleotides with complementary and non-complementary sequences. The n-and p-type silicon(1 1 1) samples were covalently linked to DNA molecules via direct Si-C linkages without any intervening oxide layer. Exposure to solutions containing DNA oligonucleotides with the complementary sequence produced significant changes in both real and imaginary components of the electrical impedance, while exposure to DNA with non-complementary sequences generated negligible responses. These changes in electrical properties were corroborated with fluorescence measurements and were reproduced in multiple hybridization-denaturation cycles. The ability to detect DNA hybridization is strongly frequency-dependent. Modeling of the response and comparison of results on different silicon bulk doping shows that the sensitivity to DNA hybridization arises from DNA-induced changes in the resistance of the silicon substrate and the resistance of the molecular layers.
Biosensor integration on Si-based devices: Feasibility studies and examples
Sensors and Actuators B: Chemical, 2013
ABSTRACT Feasibility studies and examples of integration of Si-based miniaturized biosensors are discussed. We investigated three main issues: (i) device surface functionalization, (ii) biological molecule functionality after immobilization and (iii) biosensor working principle using electrical transduction mechanism in order to fabricate electrolyte-insulator-semiconductor (EIS) and, in the near future, ion-sensitive field-effect transistor (ISFET) biosensors.We compared a well established method for the immobilization of bio-molecules on Si oxide with a new immobilization protocol, both providing a covalent bonding on SiO2 surfaces of proteins (metallothioneines) enzymes (glucose oxidase, horse radish peroxidase), or DNA strands. The process steps were characterized by means of contact angle, XPS and TEM measurements. The compatibility with Ultra Large Scale Integration (ULSI) technology of the two protocols was also studied. The results strongly encourage to use the new optimized protocol to accomplish both ULSI compatibility and biological molecules correct functionalization. The electrical characterization of MOS-like capacitors with ssDNA anchored on the SiO2 dielectric, allowed us to conclude that the structures tested are sensitive to DNA immobilization and hybridization, as demonstrated by a positive shift in the VFB of +0.47 ± 0.04 V after ssDNA immobilization and by a further +0.07 ± 0.02 V shift when hybridization occurs. Device working principle was proved in this way. However, our results seem to indicate that bare SiO2 surfaces cannot be used as anchoring sites for DNA in transistor applications. In fact, the immersion in solution causes the migration of H+ ions in the oxide and the formation of defects at the SiO2/Si interface.
Applied Physics Letters, 2012
In this work, metal-oxide-semiconductor (MOS)-like sensors in which deoxyribonucleic acid (DNA) strands are covalently immobilized either on Si oxide or on a gold surface were electrically characterized. Si oxide fabrication process allowed us to have a surface insensitive to the solution pH. A significant shift in the flat band voltage was measured after single strand DNA immobilization (þ0.47 6 0.04 V) and after the complementary strand binding (þ0.07 6 0.02 V). The results show that DNA sensing can be performed using a MOS structure which can be easily integrated in a more complex design, thus avoiding the problems related to the integration of micro-electrochemical cells. V C 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4747452\]
Talanta, 2019
We report on a novel DNA affinity biosensor which utilises the capture of a neutral charged single stranded (ss) morpholino DNA on a gold electrode to trigger an electrostatic repulsion of negatively charged silicotungstate anions and, in turn, enabled detection of the hybridisation of complementary base pairs. The repulsion of the anions, as a redox indicator, is reflected by a decrease in its electrochemical response with increasing target ss-DNA concentration. A theoretical framework for DNA detection by the affinity biosensor is proposed and verified by electrochemical measurements in the presence of the target ss-DNA by either dc cyclic voltammetry or Fourier transformed alternating current voltammetry (FTACV). The optimised conditions for the capture of the target ss-DNA and the electrochemical detection include 1 μM thiolated neutral morpholino oligo-nucleotide probe, hybridisation time of 10 min, 0.25 mM [α-SiW 12 O 40 ] 4-, and 25 mM phosphate buffer. In addition, the use of the 5th harmonic component of the FTACV gave the most sensitive response for the detection of the target ss-DNA. Under these conditions, the DNA affinity biosensor, based on FTACV detection, achieved a minimum detectable concentration of 0.1 pM ss-DNA and a linear concentration range of 0.1-1000 pM. The biosensor also successfully distinguished between some matched and mismatched base pairs.
Silicon nitride surfaces as active substrate for electrical DNA biosensors
Sensors and Actuators B: Chemical, 2017
Innovative study on Si3N4 surfaces for DNA electrical detection Optimized DNA grafting protocol on Si3N4 surfaces for biodetection Fully Si3N4 surface characterization by contact angle, ellipsometry, Atomic Force Microscopy, and Transmission Electron Microscopy. Surface and optical comparison between Si3N4 and SiO2 surface (reference material for DNA grafting) DNA electrical detection (C-V curves) on MIS-like capacitors VFB shift value of 0.4V upon hybridization with perfect match VFB shift value of 0.8V upon hybridization with PCR product Correlation between DNA number of bases and C-V shift
Feasibility Studies on Si-Based Biosensors
Sensors, 2009
The aim of this paper is to summarize the efforts carried out so far in the fabrication of Si-based biosensors by a team of researchers in Catania, Italy. This work was born as a collaboration between the Catania section of the Microelectronic and Microsystem Institute (IMM) of the CNR, the Surfaces and Interfaces laboratory (SUPERLAB) of the Consorzio Catania Ricerche and two departments at the University of Catania: the Biomedical Science and the Biological Chemistry and Molecular Biology Departments. The first goal of our study was the definition and optimization of an immobilization protocol capable of bonding the biological sensing element on a Si-based surface via covalent chemical bonds. We chose SiO 2 as the anchoring surface due to its biocompatibility and extensive presence in microelectronic devices. The immobilization protocol was tested and optimized, introducing a new step, oxide activation, using techniques compatible with microelectronic processing. The importance of the added step is described by the experimental results. We also tested different biological molecule concentrations in the immobilization solutions and the effects on the immobilized layer. Finally a MOS-like structure was designed and fabricated to test an electrical transduction OPEN ACCESS Sensors 2009, 9 3470 mechanism. The results obtained so far and the possible evolution of the research field are described in this review paper.
Electronic detection of DNA by its intrinsic molecular charge
Proceedings of the National Academy of Sciences, 2002
We report the selective and real-time detection of label-free DNA using an electronic readout. Microfabricated silicon field-effect sensors were used to directly monitor the increase in surface charge when DNA hybridizes on the sensor surface. The electrostatic immobilization of probe DNA on a positively charged poly-L-lysine layer allows hybridization at low ionic strength where field-effect sensing is most sensitive. Nanomolar DNA concentrations can be detected within minutes, and a single base mismatch within 12-mer oligonucleotides can be distinguished by using a differential detection technique with two sensors in parallel. The sensors were fabricated by standard silicon microtechnology and show promise for future electronic DNA arrays and rapid characterization of nucleic acid samples. This approach demonstrates the most direct and simple translation of genetic information to microelectronics.
Biosensors, 2021
The use of deoxyribonucleic acid (DNA) hybridization to detect disease-related gene expression is a valuable diagnostic tool. An ion-sensitive field-effect transistor (ISFET) with a graphene layer has been utilized for detecting DNA hybridization. Silicene is a two-dimensional silicon allotrope with structural properties similar to graphene. Thus, it has recently experienced intensive scientific research interest due to its unique electrical, mechanical, and sensing characteristics. In this paper, we proposed an ISFET structure with silicene and electrolyte layers for the label-free detection of DNA hybridization. When DNA hybridization occurs, it changes the ion concentration in the surface layer of the silicene and the pH level of the electrolyte solution. The process also changes the quantum capacitance of the silicene layer and the electrical properties of the ISFET device. The quantum capacitance and the corresponding resonant frequency readout of the silicene and graphene are ...