DNA based
Nanobioelectronics
PRESENTED BY
ROOPAVATH UDAY KIRAN
M.Tech 1st year
Outline
• Introduction
• DNA based Nanoelectronics
• DNA mediated assembly of Metal
nanoparticles
• Sequence specific Mole...
• The combination of biological elements with
electronics is of great interest for many
research areas.
• Inspired by biol...
The overall goal
• To create bioelectronic devices for biosensing
• Drug discovery
• Curing diseases
• To build new electr...
Recent advances in the field
• Electrical contacting of redox proteins with
electrodes.
• The use of DNA or proteins as te...
Deoxyribonucleic acid (DNA)
• Deoxyribonucleic acid (DNA) is a nucleic acid that
contains the genetic instructions for the...
DNA Based Nanoelectronics
DNA FOR MOLECULAR DEVICES
• The two- and three-dimensional assembly of complex objects
(cubes, octahedral, etc.) made with...
WHAT IS KNOWN ABOUT DNA’S ABILITY
TO CONDUCT ELECTRICAL CURRENTS?
• We just point out here the salient results that
motiva...
The molecules used for electronic applications
need to express three main features:
(a) Structuring, namely, the possibili...
• One of the main challenges with such molecules,
however, is the control of their electrical conductivity.
• Early work i...
DNA mediated Assembly of
Metal Nanoparticles
DNA - templated electronics
• Sequence-specific molecular lithography.
• The protein RecA, which is normally responsible f...
A possible scheme for the DNA templated
assembly of molecular-scale electronics
• Homologous recombination
• Addresses thr...
There are four major obstacles to the
realization of this concept.
• Biological processes need to be adopted and modified
...
• Homologous recombination is a protein-mediated
reaction by which two DNA molecules, possessing same
sequence homology, c...
Sequence Specific Molecular
Lithography
DNA molecules were first aldehyde-derivatized by reacting
them with glutaraldehyde.
Sample was incubated in an AgNO3 solut...
• RecA-mediated recombination can be harnessed to
generate the molecularly accurate DNA junctions
required for the realiza...
DNA Detection
• Through the fast increasing knowledge about
biomolecules and their interaction with other
biomolecules, the study of tho...
The DNA chip technology also comes with
some limitations.
• The miniaturized probe spots on a DNA chip need
expensive fabr...
• For instance, nowadays many hundreds of diseases
are diagnosable by the molecular analysis of DNA.
• Mainly the DNA hybr...
• Fluorescence labeling also allows multicolor
labeling, making possible the multiplexed
detection of differently labeled ...
DNA Detection using Metal Nanoparticles
• These new detection schemes are based on the
unique properties of metal nanopart...
Label-Free, Fully Electronic Detection of DNA with a
Field-Effect Transistor Array
• Field-effect sensors, especially FETs...
• Most of these sensor chips were operated as
potentiometric ISFETs and used the ion-selectivity of the
solid–liquid inter...
Last but not least
• the other way to pursue DNA-based
nanoelectronics is by looking at derivatives that
may exhibit intri...
Applications of Hybrid Nanobioelectronic systems
• Nanoelectronics for the future. The fascinating
world of the bio–self-a...
• Environmental quality. Distinguishing dioxin isomers for
cleaning up polluted sites, improving production
efficiency of ...
References:
• Nanobioelectronics - for Electronics,Biology,
and Medicine – Edited by Andreas
Offenhausser and Ross Rinaldi...
Dna based nanobioelectronics
Dna based nanobioelectronics
Dna based nanobioelectronics
Dna based nanobioelectronics
Dna based nanobioelectronics
Dna based nanobioelectronics
Dna based nanobioelectronics
Dna based nanobioelectronics
Dna based nanobioelectronics
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Dna based nanobioelectronics

  1. 1. DNA based Nanobioelectronics PRESENTED BY ROOPAVATH UDAY KIRAN M.Tech 1st year
  2. 2. Outline • Introduction • DNA based Nanoelectronics • DNA mediated assembly of Metal nanoparticles • Sequence specific Molecular Lithography • DNA detection with Metallic nanoparticles
  3. 3. • The combination of biological elements with electronics is of great interest for many research areas. • Inspired by biological signal processes • To explore ways of manipulating, assembling, and applying biomolecules and cells on integrated circuits, joining biology with electronic devices. INTRODUCTION
  4. 4. The overall goal • To create bioelectronic devices for biosensing • Drug discovery • Curing diseases • To build new electronic systems based on biologically inspired concepts • Having tools similar in size to biomolecules enables us to manipulate, measure, and (in the future) control them with electronics, ultimately connecting their unique functions.
  5. 5. Recent advances in the field • Electrical contacting of redox proteins with electrodes. • The use of DNA or proteins as templates to assemble nanoparticles . • Use of nanoelectrodes, nano-objects, and nanotools in living cells and tissue, for both fundamental biophysical studies and cellular signaling detection and nanowires. • Functional connection of neuronal signal processing elements and electronics in order to build brain–machine interfaces and future information systems.
  6. 6. Deoxyribonucleic acid (DNA) • Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. • DNA is a long polymer made from repeating units called nucleotides. The DNA chain is 22 to 24 Å wide and one nucleotide unit is 3.3 Å long. • DNA polymers can be enormous molecules containing millions of nucleotides. For instance, the largest human chromosome is 220 million base pairs long.
  7. 7. DNA Based Nanoelectronics
  8. 8. DNA FOR MOLECULAR DEVICES • The two- and three-dimensional assembly of complex objects (cubes, octahedral, etc.) made with DNA (Seeman 1998, 2003) onto organized chips to recognize and position other biological materials, with applications in diagnostics and medicine. • To explore the conductivity of DNA, Alternatively, if measurable currents cannot be sustained by DNA molecules, another interesting strategy is to realize hybrid objects (metal nanoparticles/ wires, proteins/antibodies, etc.) in which electrons move and carry current flows, templated by DNA helices at selected locations This route also allows to embed conducting objects into the hybrid architectures, to realize, e.g., a carbon nanotube DNA-templated nanotransistor Both of these ways could lead to the development of DNA based molecular electronics.
  9. 9. WHAT IS KNOWN ABOUT DNA’S ABILITY TO CONDUCT ELECTRICAL CURRENTS? • We just point out here the salient results that motivated the pursuit of optimized measurement setups on one hand, and of DNA-derivatives and mimics beyond native- DNA on the other hand. • The desired “mutants” should exhibit enhanced conductivity and/or other exploitable functions, whereas maintaining the inherent recognition and structuring traits of native Watson-Crick DNA that are demanded for self-assembling.
  10. 10. The molecules used for electronic applications need to express three main features: (a) Structuring, namely, the possibility to tailor their structural properties (composition, length, etc.) “on demand”. (b) Recognition, namely, the ability to attach them to specific sites or to other target molecules. (c) Electrical functionality, namely, suitable conductivity and control of their electrical characteristics.
  11. 11. • One of the main challenges with such molecules, however, is the control of their electrical conductivity. • Early work in this field has yielded seemingly controversial results for native-DNA, showing electrical behaviours from insulating through semiconducting to conducting, with even a single report of proximity- induced superconductivity. • Indeed, recent reviews of the experimental literature highlighted that the variety of available experiments cannot be analyzed in a unique way; for instance, electrical measurements conducted on single molecules, bundles, and networks, are not able to reveal a uniform interpretation scheme for the conductivity of DNA, because they refer to different materials or at least aggregation states.
  12. 12. DNA mediated Assembly of Metal Nanoparticles
  13. 13. DNA - templated electronics • Sequence-specific molecular lithography. • The protein RecA, which is normally responsible for homologous recombination in Escherichia coli bacteria, is utilized as a sequence-specific resist, analogous to photoresist in conventional photolithography. • The patterning information is encoded in the underlying DNA substrate rather than in glass masks. • Facilitates precise localization of molecular devices on the DNA substrate and formation of molecularly accurate junctions.
  14. 14. A possible scheme for the DNA templated assembly of molecular-scale electronics • Homologous recombination • Addresses three major challenges on the way to molecular electronics. I. Precise localization of a large number of devices at molecularly accurate addresses on the substrate. II. Construction, inter-device wiring. III. It wires the molecular network to the macroscopic world, thus bridging between the nanometer and macroscopic scales.
  15. 15. There are four major obstacles to the realization of this concept. • Biological processes need to be adopted and modified to enable the in-vitro construction of stable DNA junctions and networks with well-defined connectivity. • The hybridization of electronic materials with biological molecules needs to be advanced to the point where precise localization of electronic devices on the network is made possible. • Appropriate nanometer-scale electronic devices need to be developed. These devices should be compatible with the assembly and functionalization chemistry. • Since DNA molecules are insulating, they need to be converted into conductive wires.
  16. 16. • Homologous recombination is a protein-mediated reaction by which two DNA molecules, possessing same sequence homology, crossover at equivalent sites. • RecA is the major protein responsible for this process in Escherichia coli. • RecA proteins are polymerized on a probe DNA molecule to form a nucleoprotein filament, which is then mixed with the substrate molecules. • The nucleoprotein filament binds to the DNA substrate at homologous probe–substrate locations. • Note that RecA polymerization on the probe DNA is not sensitive to sequence. The binding specificity of the nucleoprotein filament to the substrate DNA is dictated by the probe’s sequence and its homology to the substrate molecule.
  17. 17. Sequence Specific Molecular Lithography
  18. 18. DNA molecules were first aldehyde-derivatized by reacting them with glutaraldehyde. Sample was incubated in an AgNO3 solution. The reduction of silver ions by the DNA-bound aldehyde in the unprotected segments of the substrate molecule resulted in tiny silver aggregates along the DNA skeleton. The aggregates catalyzed subsequent electroless gold deposition. Continuous highly conductive gold wire
  19. 19. • RecA-mediated recombination can be harnessed to generate the molecularly accurate DNA junctions required for the realization of elaborate DNA scaffolds. • Two types of DNA molecules which were 15 kbp and 4.3 kbp long respectively, were prepared. • The short molecule was homologous to a 4.3 kbp segment at one end of the long molecule. • The RecA was first polymerized on the short molecules and then reacted with the long molecules. • The recombination reaction led to the formation of a stable, three-armed junction with two 4.3 kbp-long arms and an 11 kbp-long third arm.
  20. 20. DNA Detection
  21. 21. • Through the fast increasing knowledge about biomolecules and their interaction with other biomolecules, the study of those biorecognition events has become more and more important. • One of the most remarkable technologies that had a strong impact on DNA detection is probably the DNA chip (or gene chip) technology. • This allows researchers to conduct thousands or even millions of different DNA sequence tests simultaneously on a single chip or array.
  22. 22. The DNA chip technology also comes with some limitations. • The miniaturized probe spots on a DNA chip need expensive fabrication procedures, which are also used in microfabrication. • The readout of the DNA arrays must be miniaturized. Finally, the detection scheme must be sensitive enough to detect just a few copies of target and selective enough to discriminate between target DNAs with slightly different compositions.  Solution to the above demerit - DNA Labelling : • DNA labeled with fluorescent dyes in combination with confocal fluorescence imaging of DNA chips has provided the high sensitivity needed
  23. 23. • For instance, nowadays many hundreds of diseases are diagnosable by the molecular analysis of DNA. • Mainly the DNA hybridization reaction is used for the detection of unknown DNA, where the target (unknown single-stranded DNA; ssDNA) is identified, when it forms a double-stranded (dsDNA) helix structure with it complementary probe (known ssDNA). • By labeling of either the target DNA or the probe DNA, the hybridization reaction can be detected by radiochemical, fluorescence, electrochemical, microgravimetric, enzymatic, and electroluminescence methods
  24. 24. • Fluorescence labeling also allows multicolor labeling, making possible the multiplexed detection of differently labeled single-stranded DNA targets on one array. • However, fluorescent dyes have significant drawbacks; • Expensive • Susceptible to photobleaching • Broad emission and absorption bands, which limit the number of dyes. These disadvantages have limited the use of DNA chips mainly to specialized laboratories
  25. 25. DNA Detection using Metal Nanoparticles • These new detection schemes are based on the unique properties of metal nanoparticles, such as  Large optical extinction and scattering coefficients.  Catalytic activity, and surface electronics. metal nanoparticles have approached as alternative labels in a variety of DNA detection schemes. • Most notably, gold nanoparticles have been used for the DNA detection, because they can be easily modified with biomolecules. • However, other metal nanoparticles, such as Ag, Pt, and Pd, have also been used for DNA detection
  26. 26. Label-Free, Fully Electronic Detection of DNA with a Field-Effect Transistor Array • Field-effect sensors, especially FETs, offer an alternative approach for the label-free detection of DNA with a direct electrical readout . • Recently, the detection limit of potentiometric field- effect sensors was enhanced such that single nucleotide polymorphisms (SNPs) were successfully detected. • The sensors used the field-effect at the electrolyte-oxide- semiconductor (EOS) interface, which was firstly described for ion-selective field-effect transistors (ISFET). • Typically, the response of such devices is interpreted as shift of the flat-band voltage of the field effect structure
  27. 27. • Most of these sensor chips were operated as potentiometric ISFETs and used the ion-selectivity of the solid–liquid interface or artificial molecular membranes, which were attached to the FET gate structure. • In this context, the dc as well as the ac readout of the FETs has been reported and the influence of a biomembrane attached to the transistor gate structure has been described. The ISFET structure can be highly integrated to multichannel sensors by using standard industrial processes. • A miniaturized, low-cost, fast readout, highly integrated, and addressable multichannel sensor with sensitivity high enough to detect SNPs, would be the ideal device for genetic testing and medical diagnostics.
  28. 28. Last but not least • the other way to pursue DNA-based nanoelectronics is by looking at derivatives that may exhibit intrinsic conductivity better than the double helix. One of the most appealing candidates in the guanine quadruple helix G4- DNA. • Other viable candidates are DNA hybrids with metal ions and double helices in which the native bases are substituted with more aromatic bases that may improve the longitudinal π-overlap
  29. 29. Applications of Hybrid Nanobioelectronic systems • Nanoelectronics for the future. The fascinating world of the bio–self-assembly provides new opportunities and directions for future electronics, opening the way to a new generation of computational systems based on biomolecules and biostructures at the nanoscale. • Life sciences. Rapid pharmaceutical discovery and toxicity screening using arrays of receptors on an integrated circuit, with the potential to develop targeted “smart drugs.” • Medical diagnostics. Rapid, inexpensive, and broad-spectrum point-of-use human and animal screening for antibodies specific to infections
  30. 30. • Environmental quality. Distinguishing dioxin isomers for cleaning up polluted sites, improving production efficiency of naturally derived polysaccharides such as pectin and cellulose, and measuring indoor air quality for “sick” buildings. • Food safety. Array sensors for quality control and for sensing bacterial toxins. • Crop protection. High-throughput screening of pesticide and herbicide candidates. • Military and civilian defense. Ultrasensitive, broad- spectrum detection of biological warfare agents and chemical detection of antipersonnel land mines, screening passengers and baggage at airports, and providing early warning for toxins from virulent bacterial strains.
  31. 31. References: • Nanobioelectronics - for Electronics,Biology, and Medicine – Edited by Andreas Offenhausser and Ross Rinaldi. • Nanobiotechnology Concepts, Applications and Perspectives Edited by Christof M. Niemeyer and Chad A. Mirkin. • Yubing Xie - The nanobiotechnology handbook-CRC Press – Taylor - Francis (2013)

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