Home
Search
Collections
Journals
About
Contact us
My IOPscience
DNA sequencing: nanotechnology unravels the code for life
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2015 Nanotechnology 26 310201 (http://iopscience.iop.org/0957-4484/26/31/310201) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 165.123.34.86 This content was downloaded on 21/07/2015 at 12:50
Please note that terms and conditions apply.
Nanotechnology Nanotechnology 26 (2015) 310201 (2pp)
doi:10.1088/0957-4484/26/31/310201
Editorial
DNA sequencing: nanotechnology unravels the code for life Anna Demming Temple Circus, Temple Way, Bristol, BSI 6HG, UK E-mail: [email protected]
the observed currents, fluctuations in currents and the frequency characteristics of these fluctuations. The nanopores themselves are produced in a range of materials with various differing advantages. Cynthia J Burrows, Henry S White and colleagues at Utah University in the US describe the potential for using nanopores in haemolysin [6]—lipid and protein materials that occur naturally in living organisms. Their investigations look at using the nanopores for identifying epigenetic markers, as well as damage to DNA resulting from oxidation or deamination, photochemical damage, and base release. They show that haemolysin pores can be successfully used to identify benzo[a]pyrene diol epoxide (BPDE) adducts on the chain. Metabolism of the carcinogenic precursor benzo[a]pyrene produces BPDE, so the technique may help determine an individual’s susceptibility to certain cancers. The collection also includes work demonstrating the potential of new materials. In their theoretical work Ralph H Scheicher and Rodrigo G Amorim at Uppsala University in Sweden investigate the potential of silicene for nanopore sequencing applications [7]. “Our findings suggest that silicene could be utilized as an integrated-circuit biosensor as part of a lab-on-a-chip device for DNA sequencing”, they conclude. The verdict for another 2D material may be more challenging. In their article, Cees Dekker and colleagues at the Delft University of Technology in the Netherlands report studies of the low-frequency noise in ionic currents [8]. They compare graphene, which is attracting a great deal of attention for nanopore sequencing at present, and the more traditional material silicon nitride and find that the noise is typically two orders of magnitude greater for graphene. “This is a drawback as it significantly lowers the signal-to-noise ratio in DNA translocation experiments”, they point out. Jan Linnros and colleagues at the KTH Royal Institute of Technology in Sweden considered silicon membranes in their work, which focuses on the feasibility and applications of electrochemically etched nanopore arrays [9]. Existing fabrication techniques for inorganic nanopores, such as focused
“We believe that the DNA is a code”, Francis Crick wrote to his twelve year old son in 1953. “That is, the order of the bases (the letters) makes one gene different to another” [1]. The letter—bristling with excitement contained one of the first descriptions of how DNA codes genetic information, and was shortly followed up with a letter to Nature [2]. Since then the contest has been set to unravel the ‘code’ hidden in the DNA of living organisms, a challenge with benefits in evolutionary biology and ecology as well as applications in forensics and a kind of ‘personalized medicine’ that is optimized to suit the individual’s genetic make up. This year Nanotechnology has been preparing a focus collection with guest editors Stuart Lindsay (Arizona State University, US) and Daniel Branton (Harvard University, US) to highlight articles reporting the latest results and developments that use nanostructures to push the frontiers in DNA sequencing technology [3]. The two main drivers in next-generation DNA sequencing technology are arguably increasing the speed of DNA reading and reducing the cost, both of which are likely to be tackled using nanotechnology. “Nanopores are being hailed as a potential next-generation DNA sequencer that could provide cheap, high-throughput DNA analysis”, Spencer Carson’ Meni Wanunu and researchers at Northeastern University in the US, suggest in their review [4]. They go on to provide a detailed overview of developments in the field including detection schemes and techniques for DNA motion control. While nanopore devices traditionally operate by detecting an ion current, another approach is to monitor the tunneling current between functionalised electrodes as the molecule passes between them, an approach described as ‘recognition tunneling’. Lindsay and colleagues at Arizona State University and Stony Brook University highlight the potential of the approach since it is sensitive to single bases, and a working prototype has already been demonstrated [5]. Their paper addresses some of the fundamental issues in the theory of recognition tunneling, including the magnitude of 0957-4484/15/310201+02$33.00
1
© 2015 IOP Publishing Ltd Printed in the UK
Nanotechnology 26 (2015) 310201
Editorial
electron beam or ion beam drilling, do not readily scale up efficiently for fabricating arrays. The team demonstrate the capability of electrochemically etching nanopores as small as 7 nm in diameter through membranes 50–100 nm thick. ‘Such a simultaneous, multipore array fabrication method is advantageous compared to e-beam ‘drilling’ techniques as it enables parallel (optical) detection of (fluorophore-labeled) bio-molecules’, they explain in their report. With the mounting interest in the possible use of laser optics for manipulating DNA and plasmonic techniques for measuring the translocation, the effects of associated temperature rises become increasingly relevant. Daniel V Verschueren, Magnus P Jonsson, and Cees Dekker at Delft University of Technology present the first systematic study of the temperature dependence of DNA translocation through inorganic solid-state nanopores [10]. The work provides a useful extension to existing theoretical models of these systems. There is as yet still no consensus of opinion as to what degree the work of Watson and Crick was an extension of the work of Rosamund Franklin, who was also working on DNA in the 1950s although in a separate lab. Her work with Raymond Gosling containing ‘photograph 51’, an x-ray diffraction image that likely contributed to Watson and Crick’s proposal of a double helical structure for DNA, was published as supporting evidence in the same issue of Nature as Crick and Watson’s letter [11]. Gosling passed away on the 18 May earlier this year, but the controversy over the due accreditation for the discovery continues. Altogether the combined efforts in DNA research, both in the 1950s and since, have invited science to engage in unraveling some of the most profound miracles of everyday life. ‘Science and everyday life cannot and should not be separated’, wrote the undergraduate Franklin to her father in defense of her scientific outlook [12], and her words proved very fitting for her later work. The potential applications of DNA sequencing and related technologies may make energetic demands on both the imaginations and judgement of the people wielding these new technologies. At the same time
they have also inspired remarkable feats of scientific progress as described in the articles of the Nanotechnology focus collection dedicated to DNA sequencing.
References [1] The order of the bases (the letters) makes one gene different from another…You can now see how nature makes copies of the genes (http//smithsonianmag.com/history/documentdeep-dive-francis-crick-explains-secret-life-180947946/? no-ist) [2] Watson J D and Crick F H C 1953 Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid Nature 171 737–8 [3] Nanotechnology Focus on DNA Sequencing (http:// iopscience.iop.org/0957-4484/page/FocusDNA_sequencing) [4] Carson S and Wanunu M 2015 Challenges in DNA motion control and sequence readout using nanopore devices Nanotechnology 26 074004 [5] Krstić P, Ashcroft B and Stuart Lindsay S 2015 Physical model for recognition tunnelling Nanotechnology 26 084001 [6] Perera R T, Fleming A M, Johnson R P, Burrows C J and White H S 2015 Detection of benzo[a]pyrene-guanine adducts in single-stranded DNA using the α-hemolysin nanopore Nanotechnology 26 074002 [7] Amorim R G and Scheicher R H 2015 Silicene as a new potential DNA sequencing device Nanotechnology 26 154002 [8] Heerema S J, Schneider G F, Rozemuller M, Vicarelli L, Zandbergen H W and Dekker C 2015 1/f noise in graphene nanopores Nanotechnology 26 074001 [9] Schmidt T, Zhang M, Sychugov I, Roxhead N and Linnros J 2015 Nanotechnology 26 314001 [10] Verschueren D V, Jonsson M P and Dekker C 2015 Temperature dependence of DNA translocations through solid-state nanopores Nanotechnology 26 234004 [11] Franklin R and Gosling R G 1953 Molecular configuration in sodium thymonucleate Nature 171 740–1 [12] The Rosalind Franklin Papers The National Library of Medicine (http://profiles.nlm.nih.gov/ps/retrieve/Narrative/ KR/p-nid/183)
2
Search
Collections
Journals
About
Contact us
My IOPscience
DNA sequencing: nanotechnology unravels the code for life
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2015 Nanotechnology 26 310201 (http://iopscience.iop.org/0957-4484/26/31/310201) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 165.123.34.86 This content was downloaded on 21/07/2015 at 12:50
Please note that terms and conditions apply.
Nanotechnology Nanotechnology 26 (2015) 310201 (2pp)
doi:10.1088/0957-4484/26/31/310201
Editorial
DNA sequencing: nanotechnology unravels the code for life Anna Demming Temple Circus, Temple Way, Bristol, BSI 6HG, UK E-mail: [email protected]
the observed currents, fluctuations in currents and the frequency characteristics of these fluctuations. The nanopores themselves are produced in a range of materials with various differing advantages. Cynthia J Burrows, Henry S White and colleagues at Utah University in the US describe the potential for using nanopores in haemolysin [6]—lipid and protein materials that occur naturally in living organisms. Their investigations look at using the nanopores for identifying epigenetic markers, as well as damage to DNA resulting from oxidation or deamination, photochemical damage, and base release. They show that haemolysin pores can be successfully used to identify benzo[a]pyrene diol epoxide (BPDE) adducts on the chain. Metabolism of the carcinogenic precursor benzo[a]pyrene produces BPDE, so the technique may help determine an individual’s susceptibility to certain cancers. The collection also includes work demonstrating the potential of new materials. In their theoretical work Ralph H Scheicher and Rodrigo G Amorim at Uppsala University in Sweden investigate the potential of silicene for nanopore sequencing applications [7]. “Our findings suggest that silicene could be utilized as an integrated-circuit biosensor as part of a lab-on-a-chip device for DNA sequencing”, they conclude. The verdict for another 2D material may be more challenging. In their article, Cees Dekker and colleagues at the Delft University of Technology in the Netherlands report studies of the low-frequency noise in ionic currents [8]. They compare graphene, which is attracting a great deal of attention for nanopore sequencing at present, and the more traditional material silicon nitride and find that the noise is typically two orders of magnitude greater for graphene. “This is a drawback as it significantly lowers the signal-to-noise ratio in DNA translocation experiments”, they point out. Jan Linnros and colleagues at the KTH Royal Institute of Technology in Sweden considered silicon membranes in their work, which focuses on the feasibility and applications of electrochemically etched nanopore arrays [9]. Existing fabrication techniques for inorganic nanopores, such as focused
“We believe that the DNA is a code”, Francis Crick wrote to his twelve year old son in 1953. “That is, the order of the bases (the letters) makes one gene different to another” [1]. The letter—bristling with excitement contained one of the first descriptions of how DNA codes genetic information, and was shortly followed up with a letter to Nature [2]. Since then the contest has been set to unravel the ‘code’ hidden in the DNA of living organisms, a challenge with benefits in evolutionary biology and ecology as well as applications in forensics and a kind of ‘personalized medicine’ that is optimized to suit the individual’s genetic make up. This year Nanotechnology has been preparing a focus collection with guest editors Stuart Lindsay (Arizona State University, US) and Daniel Branton (Harvard University, US) to highlight articles reporting the latest results and developments that use nanostructures to push the frontiers in DNA sequencing technology [3]. The two main drivers in next-generation DNA sequencing technology are arguably increasing the speed of DNA reading and reducing the cost, both of which are likely to be tackled using nanotechnology. “Nanopores are being hailed as a potential next-generation DNA sequencer that could provide cheap, high-throughput DNA analysis”, Spencer Carson’ Meni Wanunu and researchers at Northeastern University in the US, suggest in their review [4]. They go on to provide a detailed overview of developments in the field including detection schemes and techniques for DNA motion control. While nanopore devices traditionally operate by detecting an ion current, another approach is to monitor the tunneling current between functionalised electrodes as the molecule passes between them, an approach described as ‘recognition tunneling’. Lindsay and colleagues at Arizona State University and Stony Brook University highlight the potential of the approach since it is sensitive to single bases, and a working prototype has already been demonstrated [5]. Their paper addresses some of the fundamental issues in the theory of recognition tunneling, including the magnitude of 0957-4484/15/310201+02$33.00
1
© 2015 IOP Publishing Ltd Printed in the UK
Nanotechnology 26 (2015) 310201
Editorial
electron beam or ion beam drilling, do not readily scale up efficiently for fabricating arrays. The team demonstrate the capability of electrochemically etching nanopores as small as 7 nm in diameter through membranes 50–100 nm thick. ‘Such a simultaneous, multipore array fabrication method is advantageous compared to e-beam ‘drilling’ techniques as it enables parallel (optical) detection of (fluorophore-labeled) bio-molecules’, they explain in their report. With the mounting interest in the possible use of laser optics for manipulating DNA and plasmonic techniques for measuring the translocation, the effects of associated temperature rises become increasingly relevant. Daniel V Verschueren, Magnus P Jonsson, and Cees Dekker at Delft University of Technology present the first systematic study of the temperature dependence of DNA translocation through inorganic solid-state nanopores [10]. The work provides a useful extension to existing theoretical models of these systems. There is as yet still no consensus of opinion as to what degree the work of Watson and Crick was an extension of the work of Rosamund Franklin, who was also working on DNA in the 1950s although in a separate lab. Her work with Raymond Gosling containing ‘photograph 51’, an x-ray diffraction image that likely contributed to Watson and Crick’s proposal of a double helical structure for DNA, was published as supporting evidence in the same issue of Nature as Crick and Watson’s letter [11]. Gosling passed away on the 18 May earlier this year, but the controversy over the due accreditation for the discovery continues. Altogether the combined efforts in DNA research, both in the 1950s and since, have invited science to engage in unraveling some of the most profound miracles of everyday life. ‘Science and everyday life cannot and should not be separated’, wrote the undergraduate Franklin to her father in defense of her scientific outlook [12], and her words proved very fitting for her later work. The potential applications of DNA sequencing and related technologies may make energetic demands on both the imaginations and judgement of the people wielding these new technologies. At the same time
they have also inspired remarkable feats of scientific progress as described in the articles of the Nanotechnology focus collection dedicated to DNA sequencing.
References [1] The order of the bases (the letters) makes one gene different from another…You can now see how nature makes copies of the genes (http//smithsonianmag.com/history/documentdeep-dive-francis-crick-explains-secret-life-180947946/? no-ist) [2] Watson J D and Crick F H C 1953 Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid Nature 171 737–8 [3] Nanotechnology Focus on DNA Sequencing (http:// iopscience.iop.org/0957-4484/page/FocusDNA_sequencing) [4] Carson S and Wanunu M 2015 Challenges in DNA motion control and sequence readout using nanopore devices Nanotechnology 26 074004 [5] Krstić P, Ashcroft B and Stuart Lindsay S 2015 Physical model for recognition tunnelling Nanotechnology 26 084001 [6] Perera R T, Fleming A M, Johnson R P, Burrows C J and White H S 2015 Detection of benzo[a]pyrene-guanine adducts in single-stranded DNA using the α-hemolysin nanopore Nanotechnology 26 074002 [7] Amorim R G and Scheicher R H 2015 Silicene as a new potential DNA sequencing device Nanotechnology 26 154002 [8] Heerema S J, Schneider G F, Rozemuller M, Vicarelli L, Zandbergen H W and Dekker C 2015 1/f noise in graphene nanopores Nanotechnology 26 074001 [9] Schmidt T, Zhang M, Sychugov I, Roxhead N and Linnros J 2015 Nanotechnology 26 314001 [10] Verschueren D V, Jonsson M P and Dekker C 2015 Temperature dependence of DNA translocations through solid-state nanopores Nanotechnology 26 234004 [11] Franklin R and Gosling R G 1953 Molecular configuration in sodium thymonucleate Nature 171 740–1 [12] The Rosalind Franklin Papers The National Library of Medicine (http://profiles.nlm.nih.gov/ps/retrieve/Narrative/ KR/p-nid/183)
2
