Editorial Cite This: ACS Sens. 2018, 3, 2471−2472
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Nanopores for Sensing
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not only to provide the selectivity for methylation, but also to enhance the current difference between the normal base and methylated base. To achieve selective detection of human 8oxoguanine DNA glycosylase (hOGG1), a DNA substrate is designed to bear the hOGG1-specific cleavage of 8hydroxyguanine (DOI: 10.1021/acssensors.7b00954). Then, the translocation of released output DNA duplex through the α-hemolysin nanopore is quantitatively producing the ionic current signature in complex cell extractions. With the advantage of magnetic bead separation, this method evaluates the activity of endogenous hOGG1 in crude cell extracts. More importantly, the nanopore system should have a high reproducibility to reach the goal for further application. Pelta and co-workers presented a 3D-printer-helped protocol to manufacture a microfluidic device that permits the reversible integration of a SiNx nanopore (DOI: 10.1021/acssensors.8b00700). The next step is to push the nanopore sensing technique into a higher throughput manner to meet more challenging sensing demands. Leburton et al. proposed largescale parallel DNA detection in a two-dimensional membrane where the sensing mechanism is associated with the transverse sheet currents (DOI: 10.1021/acssensors.8b00192). These are examples of nanopore sensors designed for a wide range of analytes. The nanopore-DNA sequencer, released by Oxford Nanopore Technologies, is an example of a commercial application for nanopores. But the sensing capability of nanopores goes beyond DNA sequencing, and could be used as a unique tool for sensing dynamic conformations of biomolecules, protein sequencing, discriminating protein aggregates, and more. Due to the sensitive ionic current detection, nanopore sensors offer unique label-free applications not rivaled by other single molecule techniques. In spite of this, most of the reported nanopore sensors still require motor proteins or probe molecules, which complicate the nanopore analysis and increase the cost. There is a real need to develop advanced sensing mechanisms and optimize sensitive nanopore sensing interfaces that are capable of label-free single molecule sensing in real-world samples. On November 22−23, the Chinese Nanopore Community held a meeting in Shenzhen, China, which gathered together researchers from multidisciplinary backgrounds, all working toward a future for label-free single molecule sensing methods. We believe the continuous contributions from chemistry, biophysics, informatics and nanoscience will make nanopores a common sensing tool. So, we look forward to the future papers that show us how well nanopore sensors work in the “real-world”. This editorial in fact represents the last task of Professor Yitao Long for ACS Sensors. Yitao has been part of the journal from its inception, and has made major contributions to its success so far. As the Editor-in-Chief I would like to acknowledge his incredible work publicly. Not only has Yitao handled many papers with efficiency and sensitivity, but he also
he detection efficiency of a sensor is largely dependent on its interface with the analyte. To be able to measure single molecules, the first step is to miniaturize the sensing interface, which should capture and confine single molecules from bulk solutions. Some of the most well-defined systems for containing individual molecules already exist in nature, like membrane protein channels. Inspired by nature, nanopore techniques employ a single membrane protein molecule as a singlebiomolecule interface to interact with individual molecules from mixed solutions. Note that the single-biomolecule interface governs the comparable size of single biomolecules, which produces the sensitive and transient ionic current response for each molecule. The entrance domain of the nanopore is responsible for capturing, for example, a single oligonucleotide, while the inner channel region dominates the translocation process. As described in our recent paper in ACS Sensors (DOI: 10.1021/acssensors.8b00021), the site-directed mutagenesis of key amino acids at the entrance could modulate the selectivity of the nanopore sensor. Meanwhile, the single site substitution at the inner wall creates an optimal interaction with the single-biomolecule interface, which ensures the sensitivity of the sensor. Therefore, manipulation of any residue in a biological nanopore could influence the singlebiomolecule interface at the subnanometer scale. This characteristic benefits the sophisticated design of sensing interfaces for advanced biosensing. The biomimetic solid-state nanopore uses the exterior change effect to control the selectivity (DOI: 10.1021/ acssensors.7b00793). In this way, nanopores have been exploited to develop ultrasensitive sensors, not only to understand fundamental biochemical systems, but also to achieve real sample detection for point-of-care testing. The review from Kasianowicz and co-workers summarizes broad applications of nanopores for the detection of ions, polymers, proteins, and nanoparticles (DOI: 10.1021/acssensors.7b00680). However, questions still remain around how much further nanopore technology must develop to achieve real sample detection in generalized point-of-care testing. In ACS Sensors this year, there were several papers that highlight the challenges of nanopore sensors for qualitative and quantitative detection of complex samples. To achieve selective detection, the novel design of the recognition probe has been proposed to generate the characteristic current signature for the target. For example, Codin and co-workers presented a DNA origami-based approach for molecular assembly in which a thin SiNx nanopore is capable of identifying molecular substructure along the DNA scaffold (DOI: 10.1021/ acssensors.7b00628). In the nanopore, the small target molecule could initiate a DNA displacement reaction to form a protrusion on a molecular scaffold that generates a distinguishable ionic current signature. Similarly, Platt et al. designed a capture DNA probe that could be bound to the targeted methylated DNA (DOI: 10.1021/acssensors.7b00935). Here, the methylation antibody was employed, © 2018 American Chemical Society
Received: November 29, 2018 Published: December 28, 2018 2471
DOI: 10.1021/acssensors.8b01501 ACS Sens. 2018, 3, 2471−2472
ACS Sensors
Editorial
organized our China Roadshow in 2017. This was a monumental task. He has been pivotal in making ACS Sensors a home for the best sensing research from China as well as motivating the nanopore community to embrace the journal. We are very proud of the nanopore papers that have been published in the journal, and Yitao has played a major role in attracting these papers. He has also become one of my closest friends in science, and I will always fondly remember the many hours we spent walking along the waterfront in Qingdao one evening in April talking about where we thought nanoscale electrochemistry was going. So, Yitao will be sorely missed by all of us at ACS Sensors. He leaves a large hole in our team, but we are happy that he is moving to Chemical Science to make sure the analytical chemistry part of that journal has a steady hand guiding it forward. Thank you Yitao from me and the entire team at ACS Sensors.
Yitao Long,* Associate Editor East China University of Science and Technology, Shanghai, China
J. Justin Gooding, Editor-in-Chief
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The University of New South Wales, Sydney, Australia
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Yitao Long: 0000-0003-2571-7457 J. Justin Gooding: 0000-0002-5398-0597 Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.
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DOI: 10.1021/acssensors.8b01501 ACS Sens. 2018, 3, 2471−2472