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1
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Zhao Y, Wang X, Sun T, Shan P, Zhan Z, Zhao Z, Jiang Y, Qu M, Lv Q, Wang Y, Liu P, Chen S. Artificial intelligence-driven electrochemical immunosensing biochips in multi-component detection. BIOMICROFLUIDICS 2023; 17:041301. [PMID: 37614678 PMCID: PMC10444200 DOI: 10.1063/5.0160808] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 08/01/2023] [Indexed: 08/25/2023]
Abstract
Electrochemical Immunosensing (EI) combines electrochemical analysis and immunology principles and is characterized by its simplicity, rapid detection, high sensitivity, and specificity. EI has become an important approach in various fields, such as clinical diagnosis, disease prevention and treatment, environmental monitoring, and food safety. However, EI multi-component detection still faces two major bottlenecks: first, the lack of cost-effective and portable detection platforms; second, the difficulty in eliminating batch differences and accurately decoupling signals from multiple analytes. With the gradual maturation of biochip technology, high-throughput analysis and portable detection utilizing the advantages of miniaturized chips, high sensitivity, and low cost have become possible. Meanwhile, Artificial Intelligence (AI) enables accurate decoupling of signals and enhances the sensitivity and specificity of multi-component detection. We believe that by evaluating and analyzing the characteristics, benefits, and linkages of EI, biochip, and AI technologies, we may considerably accelerate the development of EI multi-component detection. Therefore, we propose three specific prospects: first, AI can enhance and optimize the performance of the EI biochips, addressing the issue of multi-component detection for portable platforms. Second, the AI-enhanced EI biochips can be widely applied in home care, medical healthcare, and other areas. Third, the cross-fusion and innovation of EI, biochip, and AI technologies will effectively solve key bottlenecks in biochip detection, promoting interdisciplinary development. However, challenges may arise from AI algorithms that are difficult to explain and limited data access. Nevertheless, we believe that with technological advances and further research, there will be more methods and technologies to overcome these challenges.
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Affiliation(s)
- Yuliang Zhao
- School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao 066000, Hebei, China
| | - Xiaoai Wang
- School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao 066000, Hebei, China
| | - Tingting Sun
- School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao 066000, Hebei, China
| | - Peng Shan
- School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao 066000, Hebei, China
| | - Zhikun Zhan
- School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao 066000, Hebei, China
| | - Zhongpeng Zhao
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China
| | - Yongqiang Jiang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China
| | - Mingyue Qu
- The PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
| | - Qingyu Lv
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China
| | - Ying Wang
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Peng Liu
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China
| | - Shaolong Chen
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China
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2
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Metaxiotou Z, Bissig H, Batista E, do Céu Ferreira M, Timmerman A. Metrology in health: challenges and solutions in infusion therapy and diagnostics. BIOMED ENG-BIOMED TE 2023; 68:3-12. [PMID: 36351241 DOI: 10.1515/bmt-2022-0045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 10/24/2022] [Indexed: 11/10/2022]
Abstract
The significance of Metrology in infusion therapy and diagnostics, both critical in health care safety and quality, is discussed in this article. Although infusion therapy is the most used form of drug administration, infusion errors are often made with reported dramatic effects in different applications, especially in neonatology. Adverse incidents, morbidity, and mortality have often been traced back to poor or inaccurate dosing. For critical infusion applications to vulnerable patients, well-controlled medication administration might be accomplished by improved dosing accuracy, traceable measurement of volume, flow, and pressure in existing drug delivery devices and in-line sensors operating at very low flow rates. To this end, the contribution of recently upgraded metrological infrastructures in European Metrology Institutes to a safer infusion therapy in health care is described in detail. Diagnostics, on the other hand is a sector characterized by rapid developments further triggered recently by the necessity for the management and prevention of infectious diseases like COVID-19. In this context, the impact of metrology in future large-scale commercialization of next generation diagnostics (e.g., point-of-care) is highlighted. Moreover, the latest contributions of Metrology in the development of traceable testing methods and protocols to ensure the sensitivity and accuracy of these devices are described.
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Affiliation(s)
- Zoe Metaxiotou
- Mechanical Measurements Department, Laboratory of Flow and Volume, NQIS/EIM, Thessaloniki, Greece
| | - Hugo Bissig
- Physics, Federal Institute of Metrology METAS, Bern-Wabern, Switzerland
| | | | - Maria do Céu Ferreira
- Metrology Department, IPQ, Caparica, Portugal.,Research Centre in Industrial Engineering, Management and Sustainability, Lusofona University, Caparica, Portugal
| | - Annemoon Timmerman
- Department of Medical Technology and Clinical Physics, University Medical Center, Utrecht, Netherlands
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3
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Xu X, Valavanis D, Ciocci P, Confederat S, Marcuccio F, Lemineur JF, Actis P, Kanoufi F, Unwin PR. The New Era of High-Throughput Nanoelectrochemistry. Anal Chem 2023; 95:319-356. [PMID: 36625121 PMCID: PMC9835065 DOI: 10.1021/acs.analchem.2c05105] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Indexed: 01/11/2023]
Affiliation(s)
- Xiangdong Xu
- Department
of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
| | | | - Paolo Ciocci
- Université
Paris Cité, ITODYS, CNRS, F-75013 Paris, France
| | - Samuel Confederat
- School
of Electronic and Electrical Engineering and Pollard Institute, University of Leeds, Leeds LS2 9JT, U.K.
- Bragg
Centre for Materials Research, University
of Leeds, Leeds LS2 9JT, U.K.
| | - Fabio Marcuccio
- School
of Electronic and Electrical Engineering and Pollard Institute, University of Leeds, Leeds LS2 9JT, U.K.
- Bragg
Centre for Materials Research, University
of Leeds, Leeds LS2 9JT, U.K.
- Faculty
of Medicine, Imperial College London, London SW7 2AZ, United Kingdom
| | | | - Paolo Actis
- School
of Electronic and Electrical Engineering and Pollard Institute, University of Leeds, Leeds LS2 9JT, U.K.
- Bragg
Centre for Materials Research, University
of Leeds, Leeds LS2 9JT, U.K.
| | | | - Patrick R. Unwin
- Department
of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
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4
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Wei X, Wang X, Zhang Z, Luo Y, Wang Z, Xiong W, Jain PK, Monnier JR, Wang H, Hu TY, Tang C, Albrecht H, Liu C. A click chemistry amplified nanopore assay for ultrasensitive quantification of HIV-1 p24 antigen in clinical samples. Nat Commun 2022; 13:6852. [PMID: 36369146 PMCID: PMC9651128 DOI: 10.1038/s41467-022-34273-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 10/19/2022] [Indexed: 11/13/2022] Open
Abstract
Despite major advances in HIV testing, ultrasensitive detection of early infection remains challenging, especially for the viral capsid protein p24, which is an early virological biomarker of HIV-1 infection. Here, To improve p24 detection in patients missed by immunological tests that dominate the diagnostics market, we show a click chemistry amplified nanopore (CAN) assay for ultrasensitive quantitative detection. This strategy achieves a 20.8 fM (0.5 pg/ml) limit of detection for HIV-1 p24 antigen in human serum, demonstrating 20~100-fold higher analytical sensitivity than nanocluster-based immunoassays and clinically used enzyme-linked immunosorbent assay, respectively. Clinical validation of the CAN assay in a pilot cohort shows p24 quantification at ultra-low concentration range and correlation with CD4 count and viral load. We believe that this strategy can improve the utility of p24 antigen in detecting early infection and monitoring HIV progression and treatment efficacy, and also can be readily modified to detect other infectious diseases.
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Affiliation(s)
- Xiaojun Wei
- Biomedical Engineering Program, University of South Carolina, Columbia, SC, 29208, USA
- Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, USA
| | - Xiaoqin Wang
- Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, USA
| | - Zehui Zhang
- Biomedical Engineering Program, University of South Carolina, Columbia, SC, 29208, USA
| | - Yuanyuan Luo
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Zixin Wang
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Wen Xiong
- Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, USA
| | - Piyush K Jain
- Department of Chemical Engineering, University of Florida, Gainesville, FL, 32611, USA
- Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, 32610, USA
- UF Health Cancer Center, University of Florida, Gainesville, FL, 32608, USA
| | - John R Monnier
- Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, USA
| | - Hui Wang
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Tony Y Hu
- Center for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, 70112, USA
- Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Chuanbing Tang
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Helmut Albrecht
- Department of Internal Medicine, School of Medicine, University of South Carolina, Columbia, SC, 29209, USA
- Center of Infectious Diseases Research and Policy, Prisma Health, Columbia, SC, 29203, USA
| | - Chang Liu
- Biomedical Engineering Program, University of South Carolina, Columbia, SC, 29208, USA.
- Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, USA.
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5
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Liu L, Luo C, Zhang J, He X, Shen Y, Yan B, Huang Y, Xia F, Jiang L. Synergistic Effect of Bio-Inspired Nanochannels: Hydrophilic DNA Probes at Inner Wall and Hydrophobic Coating at Outer Surface for Highly Sensitive Detection. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2201925. [PMID: 35980948 DOI: 10.1002/smll.202201925] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 06/16/2022] [Indexed: 06/15/2023]
Abstract
During the past few decades, bio-inspired nanochannels have been well developed and applied in biosensing, energy transfer, separation, and so on. Here, inspired by the synergistic effect of biological nanopores, biomimetic solid-state nanochannels with hydrophilic DNA probes at the inner wall (DNA@IWHydrophilic ) and hydrophobic coating at the outer surface (None@OSHydrophobic ) are designed. To demonstrate their prompted sensing properties, Hg2+ and its specific probe are selected as target and hydrophilic DNA probes, respectively. Compared with the traditional solid-state nanochannels with hydrophilic probes distributed on both the inner wall and outer surface, the nanochannels with DNA@IWHydrophilic +None@OSHydrophobic significantly decrease the limit of detection (LOD) by 105 -fold. The obvious improvement of sensitivity (with LOD of 1 nM) is attributed to the synergistic effect: None@OSHydrophobic results in the nanochannel's effective diameter decrease and DNA@IWHydrophilic induces a specific sensing target. Meanwhile, nanomolar detection of Hg2+ in human serum and in vivo fish muscle are achieved. Through molecular dynamics simulation, the synergistic effect can be confirmed by ion fluxes increasement; the relative carbon nanotube increases from 135.64% to 135.84%. This work improves the understanding of nanochannels' synergistic effect and provides a significant insight for nanochannels with improved sensitivity.
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Affiliation(s)
- Lingxiao Liu
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Material Science and Chemistry, China University of Geosciences, Wuhan, 430074, P. R. China
| | - Cihui Luo
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Material Science and Chemistry, China University of Geosciences, Wuhan, 430074, P. R. China
| | - Jinhuan Zhang
- Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, P. R. China
| | - Xiao He
- Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, P. R. China
- New York University-East China Normal University Center for Computational Chemistry, New York University Shanghai, Shanghai, 200062, P. R. China
| | - Ying Shen
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China
| | - Bing Yan
- School of Environmental Studies, China University of Geosciences, Wuhan, 430074, P. R. China
| | - Yu Huang
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Material Science and Chemistry, China University of Geosciences, Wuhan, 430074, P. R. China
- Zhejiang Institute, China University of Geosciences, Hangzhou, 311305, P. R. China
| | - Fan Xia
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Material Science and Chemistry, China University of Geosciences, Wuhan, 430074, P. R. China
- Zhejiang Institute, China University of Geosciences, Hangzhou, 311305, P. R. China
| | - Lei Jiang
- Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of the Ministry of Education, School of Chemistry and Environment, Beihang University, Beijing, 100191, P. R. China
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6
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Rahman M, Islam KR, Islam MR, Islam MJ, Kaysir MR, Akter M, Rahman MA, Alam SMM. A Critical Review on the Sensing, Control, and Manipulation of Single Molecules on Optofluidic Devices. MICROMACHINES 2022; 13:968. [PMID: 35744582 PMCID: PMC9229244 DOI: 10.3390/mi13060968] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/19/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023]
Abstract
Single-molecule techniques have shifted the paradigm of biological measurements from ensemble measurements to probing individual molecules and propelled a rapid revolution in related fields. Compared to ensemble measurements of biomolecules, single-molecule techniques provide a breadth of information with a high spatial and temporal resolution at the molecular level. Usually, optical and electrical methods are two commonly employed methods for probing single molecules, and some platforms even offer the integration of these two methods such as optofluidics. The recent spark in technological advancement and the tremendous leap in fabrication techniques, microfluidics, and integrated optofluidics are paving the way toward low cost, chip-scale, portable, and point-of-care diagnostic and single-molecule analysis tools. This review provides the fundamentals and overview of commonly employed single-molecule methods including optical methods, electrical methods, force-based methods, combinatorial integrated methods, etc. In most single-molecule experiments, the ability to manipulate and exercise precise control over individual molecules plays a vital role, which sometimes defines the capabilities and limits of the operation. This review discusses different manipulation techniques including sorting and trapping individual particles. An insight into the control of single molecules is provided that mainly discusses the recent development of electrical control over single molecules. Overall, this review is designed to provide the fundamentals and recent advancements in different single-molecule techniques and their applications, with a special focus on the detection, manipulation, and control of single molecules on chip-scale devices.
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Affiliation(s)
- Mahmudur Rahman
- Department of Electrical and Electronic Engineering, Dhaka University of Engineering & Technology, Gazipur 1707, Bangladesh; (M.R.); (K.R.I.); (M.R.I.); (M.A.); (M.A.R.)
| | - Kazi Rafiqul Islam
- Department of Electrical and Electronic Engineering, Dhaka University of Engineering & Technology, Gazipur 1707, Bangladesh; (M.R.); (K.R.I.); (M.R.I.); (M.A.); (M.A.R.)
| | - Md. Rashedul Islam
- Department of Electrical and Electronic Engineering, Dhaka University of Engineering & Technology, Gazipur 1707, Bangladesh; (M.R.); (K.R.I.); (M.R.I.); (M.A.); (M.A.R.)
| | - Md. Jahirul Islam
- Department of Electrical and Electronic Engineering, Khulna University of Engineering & Technology, Khulna 9203, Bangladesh;
| | - Md. Rejvi Kaysir
- Department of Electrical and Computer Engineering, University of Waterloo, 200 University Ave. W, Waterloo, ON N2L 3G1, Canada;
- Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Ave. W, Waterloo, ON N2L 3G1, Canada
| | - Masuma Akter
- Department of Electrical and Electronic Engineering, Dhaka University of Engineering & Technology, Gazipur 1707, Bangladesh; (M.R.); (K.R.I.); (M.R.I.); (M.A.); (M.A.R.)
| | - Md. Arifur Rahman
- Department of Electrical and Electronic Engineering, Dhaka University of Engineering & Technology, Gazipur 1707, Bangladesh; (M.R.); (K.R.I.); (M.R.I.); (M.A.); (M.A.R.)
| | - S. M. Mahfuz Alam
- Department of Electrical and Electronic Engineering, Dhaka University of Engineering & Technology, Gazipur 1707, Bangladesh; (M.R.); (K.R.I.); (M.R.I.); (M.A.); (M.A.R.)
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7
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Wu Y, Gooding JJ. The application of single molecule nanopore sensing for quantitative analysis. Chem Soc Rev 2022; 51:3862-3885. [PMID: 35506519 DOI: 10.1039/d1cs00988e] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Nanopore-based sensors typically work by monitoring transient pulses in conductance via current-time traces as molecules translocate through the nanopore. The unique property of being able to monitor single molecules gives nanopore sensors the potential as quantitative sensors based on the counting of single molecules. This review provides an overview of the concepts and fabrication of nanopore sensors as well as nanopore sensing with a view toward using nanopore sensors for quantitative analysis. We first introduce the classification of nanopores and highlight their applications in molecular identification with some pioneering studies. The review then shifts focus to recent strategies to extend nanopore sensors to devices that can rapidly and accurately quantify the amount of an analyte of interest. Finally, future prospects are provided and briefly discussed. The aim of this review is to aid in understanding recent advances, challenges, and prospects for nanopore sensors for quantitative analysis.
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Affiliation(s)
- Yanfang Wu
- School of Chemistry and Australian Centre for NanoMedicine, The University of New South Wales, Sydney, New South Wales 2052, Australia.
| | - J Justin Gooding
- School of Chemistry and Australian Centre for NanoMedicine, The University of New South Wales, Sydney, New South Wales 2052, Australia.
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8
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van Kooten XF, Rozevsky Y, Marom Y, Ben Sadeh E, Meller A. Purely electrical SARS-CoV-2 sensing based on single-molecule counting. NANOSCALE 2022; 14:4977-4986. [PMID: 35258059 PMCID: PMC8969453 DOI: 10.1039/d1nr07787b] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 03/03/2022] [Indexed: 05/23/2023]
Abstract
The majority of RNA based COVID-19 diagnostics employ enzymatic amplification to achieve high sensitivity, but this relies on arbitrary thresholding, which complicates the comparison of test results and may lead to false outcomes. Here we introduce solid-state nanopore sensing for label-free quantification of SARS-CoV-2 RNA in clinical nasal swab samples. This PCR-free method involves reverse transcribing a target gene on the viral RNA before enzymatically digesting all but the resulting dsDNA. Ratiometric quantification of RNA abundance is achieved by single-molecule counting and length-based nanopore identification of dsDNA from a SARS-CoV-2 gene and a human reference gene. We graded nasal swab samples from >15 subjects and find that the SARS-CoV-2 ratiometric nanopore index correlates well with the reported RT-qPCR threshold cycle for positive classified samples. Remarkably, nanopore analysis also reports quantitative positive outcomes for clinical samples classified as negative by RT-qPCR, suggesting that the method may be used to diagnose COVID-19 in samples that may evade detection. We show that the sample preparation workflow can be implemented using a compact microfluidic device with integrated thermal control for semi-automated processing of extremely small sample volumes, offering a viable route towards automated, fast and affordable RNA quantification in a small and portable device.
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Affiliation(s)
| | - Yana Rozevsky
- Department of Biomedical Engineering, Technion-IIT, Haifa 32000, Israel.
| | - Yulia Marom
- Department of Biomedical Engineering, Technion-IIT, Haifa 32000, Israel.
| | - Efrat Ben Sadeh
- Department of Biomedical Engineering, Technion-IIT, Haifa 32000, Israel.
| | - Amit Meller
- Department of Biomedical Engineering, Technion-IIT, Haifa 32000, Israel.
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9
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Applications of magnetic materials in the fabrication of microfluidic-based sensing systems: Recent advances. Microchem J 2022. [DOI: 10.1016/j.microc.2021.107042] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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10
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Akhtarian S, Miri S, Doostmohammadi A, Brar SK, Rezai P. Nanopore sensors for viral particle quantification: current progress and future prospects. Bioengineered 2021; 12:9189-9215. [PMID: 34709987 PMCID: PMC8810133 DOI: 10.1080/21655979.2021.1995991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 10/16/2021] [Accepted: 10/16/2021] [Indexed: 12/24/2022] Open
Abstract
Rapid, inexpensive, and laboratory-free diagnostic of viral pathogens is highly critical in controlling viral pandemics. In recent years, nanopore-based sensors have been employed to detect, identify, and classify virus particles. By tracing ionic current containing target molecules across nano-scale pores, nanopore sensors can recognize the target molecules at the single-molecule level. In the case of viruses, they enable discrimination of individual viruses and obtaining important information on the physical and chemical properties of viral particles. Despite classical benchtop virus detection methods, such as amplification techniques (e.g., PCR) or immunological assays (e.g., ELISA), that are mainly laboratory-based, expensive and time-consuming, nanopore-based sensing methods can enable low-cost and real-time point-of-care (PoC) and point-of-need (PoN) monitoring of target viruses. This review discusses the limitations of classical virus detection methods in PoN virus monitoring and then provides a comprehensive overview of nanopore sensing technology and its emerging applications in quantifying virus particles and classifying virus sub-types. Afterward, it discusses the recent progress in the field of nanopore sensing, including integrating nanopore sensors with microfabrication technology, microfluidics and artificial intelligence, which have been demonstrated to be promising in developing the next generation of low-cost and portable biosensors for the sensitive recognition of viruses and emerging pathogens.
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Affiliation(s)
- Shiva Akhtarian
- Department of Mechanical Engineering, York University, Toronto, ON, Canada
| | - Saba Miri
- Department of Civil Engineering, York University, Toronto, ON, Canada
| | - Ali Doostmohammadi
- Department of Mechanical Engineering, York University, Toronto, ON, Canada
| | | | - Pouya Rezai
- Department of Mechanical Engineering, York University, Toronto, ON, Canada
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11
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Froehlich K, Scheuerlein MC, Ali M, Nasir S, Ensinger W. Enhancement of heavy ion track-etching in polyimide membranes with organic solvents. NANOTECHNOLOGY 2021; 33:045301. [PMID: 34644697 DOI: 10.1088/1361-6528/ac2f5a] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 10/13/2021] [Indexed: 06/13/2023]
Abstract
The effect of organic solvents on the ion track-etching of polyimide (PI) membranes is studied to enhance the nanopore fabrication process and the control over pore diameter growth. To this end, two approaches are employed to investigate the influence of organic solvents on the nanopore fabrication in PI membranes. In the first approach, the heavy ion irradiated PI samples are pretreated with organic solvents and then chemically etched with sodium hypochlorite (NaOCl) solution, resulting up to ∼4.4 times larger pore size compared to untreated ones. The second approach is based on a single-step track-etching process where the etchant (NaOCl) solution contains varying amounts of organic solvent (by vol%). The experimental data shows that a significant increase in both the bulk-etch and track-etch rates is observed by using the etchant mixture, which leads to ∼47% decrease in the nanopore fabrication time. This enhancement of nanopore fabrication process in PI membranes would open up new opportunities for their implementation in various potential applications.
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Affiliation(s)
- Kristina Froehlich
- Department of Material- and Geo-Sciences, Materials Analysis, Technische Universität Darmstadt, Alarich-Weiss-Str. 02, D-64287 Darmstadt, Germany
| | - Martin Christoph Scheuerlein
- Department of Material- and Geo-Sciences, Materials Analysis, Technische Universität Darmstadt, Alarich-Weiss-Str. 02, D-64287 Darmstadt, Germany
| | - Mubarak Ali
- Department of Material- and Geo-Sciences, Materials Analysis, Technische Universität Darmstadt, Alarich-Weiss-Str. 02, D-64287 Darmstadt, Germany
- Materials Research Department, GSI Helmholtzzentrum für Schwerionenforschung, D-64291, Darmstadt, Germany
| | - Saima Nasir
- Department of Material- and Geo-Sciences, Materials Analysis, Technische Universität Darmstadt, Alarich-Weiss-Str. 02, D-64287 Darmstadt, Germany
- Materials Research Department, GSI Helmholtzzentrum für Schwerionenforschung, D-64291, Darmstadt, Germany
| | - Wolfgang Ensinger
- Department of Material- and Geo-Sciences, Materials Analysis, Technische Universität Darmstadt, Alarich-Weiss-Str. 02, D-64287 Darmstadt, Germany
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12
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He L, Tessier DR, Briggs K, Tsangaris M, Charron M, McConnell EM, Lomovtsev D, Tabard-Cossa V. Digital immunoassay for biomarker concentration quantification using solid-state nanopores. Nat Commun 2021; 12:5348. [PMID: 34504071 PMCID: PMC8429538 DOI: 10.1038/s41467-021-25566-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 08/12/2021] [Indexed: 12/05/2022] Open
Abstract
Single-molecule counting is the most accurate and precise method for determining the concentration of a biomarker in solution and is leading to the emergence of digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores—fully electronic sensors with single-molecule sensitivity—are well suited to the task. Here we present a digital immunoassay scheme capable of reliably quantifying the concentration of a target protein in complex biofluids that overcomes specificity, sensitivity, and consistency challenges associated with the use of solid-state nanopores for protein sensing. This is achieved by employing easily-identifiable DNA nanostructures as proxies for the presence (“1”) or absence (“0”) of the target protein captured via a magnetic bead-based sandwich immunoassay. As a proof-of-concept, we demonstrate quantification of the concentration of thyroid-stimulating hormone from human serum samples down to the high femtomolar range. Further optimization to the method will push sensitivity and dynamic range, allowing for development of precision diagnostic tools compatible with point-of-care format. The concentration of a biomarker in solution can be determined by counting single molecules. Here the authors report a digital immunoassay scheme with solid-state nanopore readout to quantify a target protein and use this to measure thyroid-stimulating hormone from human serum.
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Affiliation(s)
- Liqun He
- Department of Physics, University of Ottawa, Ottawa, Canada
| | | | - Kyle Briggs
- Department of Physics, University of Ottawa, Ottawa, Canada
| | | | - Martin Charron
- Department of Physics, University of Ottawa, Ottawa, Canada
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13
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Rahman M, Sampad MJN, Hawkins A, Schmidt H. Recent advances in integrated solid-state nanopore sensors. LAB ON A CHIP 2021; 21:3030-3052. [PMID: 34137407 PMCID: PMC8372664 DOI: 10.1039/d1lc00294e] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
The advent of single-molecule probing techniques has revolutionized the biomedical and life science fields and has spurred the development of a new class of labs-on-chip based on powerful biosensors. Nanopores represent one of the most recent and most promising single molecule sensing paradigms that is seeing increased chip-scale integration for improved convenience and performance. Due to their physical structure, nanopores are highly sensitive, require low sample volume, and offer label-free, amplification-free, high-throughput real-time detection and identification of biomolecules. Over the last 25 years, nanopores have been extensively employed to detect a variety of biomolecules with a growing range of applicatons ranging from nucleic acid sequencing to ultrasensitive diagnostics to single-molecule biophysics. Nanopores, in particular those in solid-state membranes, also have the potential for integration with other technologies such as optics, plasmonics, microfluidics, and optofluidics to perform more complex tasks for an ever-expanding demand. A number of breakthrough results using integrated nanopore platforms have already been reported, and more can be expected as nanopores remain the focus of innovative research and are finding their way into commercial instruments. This review provides an overview of different aspects and challenges of nanopore technology with a focus on chip-scale integration of solid-state nanopores for biosensing and bioanalytical applications.
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Affiliation(s)
- Mahmudur Rahman
- School of Engineering, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA, 95064 USA. and Dhaka University of Engineering & Technology, Gazipur, Bangladesh
| | | | - Aaron Hawkins
- ECEn Department, Brigham Young University, 459 Clyde Building, Provo, UT, 84602 USA
| | - Holger Schmidt
- School of Engineering, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA, 95064 USA.
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14
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Song Y, Kim YT, Choi Y, Kim H, Yeom MH, Kim Y, Lee TJ, Lee KG, Im SG. All-in-One DNA Extraction Tube for Facilitated Real-Time Detection of Infectious Pathogens. Adv Healthc Mater 2021; 10:e2100430. [PMID: 34050626 DOI: 10.1002/adhm.202100430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/29/2021] [Indexed: 12/23/2022]
Abstract
An "all-in-one tube" platform is developed, where the genetic analysis involving DNA extraction, amplification, and detection can be performed in a single tube. The all-in-one tube consists of a polymerase chain reaction (PCR) tube in which the inner surface is conformally modified with a tertiary-amine-containing polymer to generate a strong electrostatic interaction with DNA. The all-in-one tube provides high DNA capture efficiency exceeding 80% from Escherichia coli O157: H7 pathogen at a wide range of DNA amount from 0.003 to 3 ng. Indeed, the use of the surface-functionalized PCR tube enables direct amplification and detection of the surface-captured DNA without the modification of standard real-time PCR instrument. Besides, this platform has sensitivity, selectivity, and reliability enough for accurate detection at the minimal infective dose of both gram-positive and negative pathogens. The all-in-one tube enables the direct molecular diagnosis, substantially reducing the labor-intensive pathogen detection steps while providing high compatibility with the currently established real-time PCR instruments, and illustrates its on-site applicability with convenience expandable to various genetic analyses including food safety testing, forensic analysis, and clinical diagnosis.
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Affiliation(s)
- Younseong Song
- Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology 291 Daehak‐ro Daejeon 34141 Republic of Korea
| | - Yong Tae Kim
- Department of Chemical Engineering & Biotechnology Korea Polytechnic University 237 Sangidaehak‐ro Siheung‐si 15073 Republic of Korea
| | - Yunho Choi
- Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology 291 Daehak‐ro Daejeon 34141 Republic of Korea
| | - Hogi Kim
- Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology 291 Daehak‐ro Daejeon 34141 Republic of Korea
| | - Min Hee Yeom
- Nanobio Application Team National NanoFab Center 291 Daehak‐ro Daejeon 34141 Republic of Korea
| | - Yesol Kim
- Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology 291 Daehak‐ro Daejeon 34141 Republic of Korea
| | - Tae Jae Lee
- Nanobio Application Team National NanoFab Center 291 Daehak‐ro Daejeon 34141 Republic of Korea
| | - Kyoung G. Lee
- Nanobio Application Team National NanoFab Center 291 Daehak‐ro Daejeon 34141 Republic of Korea
| | - Sung Gap Im
- Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology 291 Daehak‐ro Daejeon 34141 Republic of Korea
- KAIST Institute for NanoCentury Korea Advanced Institute of Science and Technology 291 Daehak‐ro Daejeon 34141 Republic of Korea
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15
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Nanodiagnostics: A review of the medical capabilities of nanopores. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2021; 37:102425. [PMID: 34174420 DOI: 10.1016/j.nano.2021.102425] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 04/22/2021] [Accepted: 05/09/2021] [Indexed: 11/20/2022]
Abstract
Modern diagnostics strive to be accurate, fast, and inexpensive in addition to properly identifying the presence of a disease, infection, or illness. Early diagnosis is key; catching a disease in its early stages can be the difference between fatality and treatment. The challenge with many diseases is that detectability of the disease scales with disease progression. Since single molecule sensors, e.g., nanopores, can sense biomolecules at low concentrations, they have the potential to become clinically relevant in many of today's medical settings. With nanopore-based sensing, lower volumes and concentrations are required for detection, enabling it to be clinically beneficial. Other advantages to using nanopores include that they are tunable to an enormous variety of molecules and boast low costs, and fabrication is scalable for manufacturing. We discuss previous reports and the potential for incorporating nanopores into the medical field for early diagnostics, therapeutic monitoring, and identifying relapse/recurrence.
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16
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Alfaro JA, Bohländer P, Dai M, Filius M, Howard CJ, van Kooten XF, Ohayon S, Pomorski A, Schmid S, Aksimentiev A, Anslyn EV, Bedran G, Cao C, Chinappi M, Coyaud E, Dekker C, Dittmar G, Drachman N, Eelkema R, Goodlett D, Hentz S, Kalathiya U, Kelleher NL, Kelly RT, Kelman Z, Kim SH, Kuster B, Rodriguez-Larrea D, Lindsay S, Maglia G, Marcotte EM, Marino JP, Masselon C, Mayer M, Samaras P, Sarthak K, Sepiashvili L, Stein D, Wanunu M, Wilhelm M, Yin P, Meller A, Joo C. The emerging landscape of single-molecule protein sequencing technologies. Nat Methods 2021; 18:604-617. [PMID: 34099939 PMCID: PMC8223677 DOI: 10.1038/s41592-021-01143-1] [Citation(s) in RCA: 197] [Impact Index Per Article: 49.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 04/02/2021] [Indexed: 02/04/2023]
Abstract
Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biological discovery and open new avenues for ultrasensitive disease diagnostics.
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Affiliation(s)
- Javier Antonio Alfaro
- International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland.
| | - Peggy Bohländer
- Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands
| | - Mingjie Dai
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Department of Systems Biology, Harvard Medical School, Boston, MA, USA
| | - Mike Filius
- Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands
| | - Cecil J Howard
- Department of Chemistry, University of Texas at Austin, Austin, TX, USA
| | - Xander F van Kooten
- Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Shilo Ohayon
- Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Adam Pomorski
- Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands
| | - Sonja Schmid
- NanoDynamicsLab, Laboratory of Biophysics, Wageningen University, Wageningen, the Netherlands
| | - Aleksei Aksimentiev
- Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Eric V Anslyn
- Department of Chemistry, University of Texas at Austin, Austin, TX, USA
| | - Georges Bedran
- International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland
| | - Chan Cao
- Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Mauro Chinappi
- Dipartimento di Ingegneria Industriale, Università di Roma Tor Vergata, Rome, Italy
| | - Etienne Coyaud
- Univ. Lille, Inserm, CHU Lille, U1192-Protéomique Réponse Inflammatoire Spectrométrie de Masse-PRISM, Lille, France
| | - Cees Dekker
- Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands
| | - Gunnar Dittmar
- Department of Infection and Immunity, Luxembourg Institute of Health, Strassen, Luxembourg
- Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | | | - Rienk Eelkema
- Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands
| | - David Goodlett
- International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland
- Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada
| | | | - Umesh Kalathiya
- International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland
| | - Neil L Kelleher
- Departments of Chemistry and Molecular Biosciences, and the Feinberg School of Medicine, Northwestern University, Evanston, IL, USA
| | - Ryan T Kelly
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
| | - Zvi Kelman
- Institute for Bioscience and Biotechnology Research, National Institute of Standards and Technology, University of Maryland, Rockville, MD, USA
- Biomolecular Labeling Laboratory, Institute for Bioscience and Biotechnology Research, Rockville, MD, USA
| | - Sung Hyun Kim
- Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands
| | - Bernhard Kuster
- Chair of Proteomics and Bioanalytics, Technische Universität München, Freising, Germany
- Bavarian Center for Biomolecular Mass Spectrometry, Freising, Germany
| | - David Rodriguez-Larrea
- Department of Biochemistry and Molecular Biology, Biofisika Institute (CSIC, UPV/EHU), Leioa, Spain
| | - Stuart Lindsay
- Biodesign Institute, School of Molecular Sciences, Department of Physics, Arizona State University, Tempe, AZ, USA
| | - Giovanni Maglia
- Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
| | - Edward M Marcotte
- Department of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX, USA
| | - John P Marino
- Institute for Bioscience and Biotechnology Research, National Institute of Standards and Technology, University of Maryland, Rockville, MD, USA
| | | | - Michael Mayer
- Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland
| | - Patroklos Samaras
- Chair of Proteomics and Bioanalytics, Technische Universität München, Freising, Germany
| | - Kumar Sarthak
- Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Lusia Sepiashvili
- University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Derek Stein
- Department of Physics, Brown University, Providence, RI, USA
| | - Meni Wanunu
- Department of Physics, Northeastern University, Boston, MA, USA
- Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA
| | - Mathias Wilhelm
- Chair of Proteomics and Bioanalytics, Technische Universität München, Freising, Germany
| | - Peng Yin
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Department of Systems Biology, Harvard Medical School, Boston, MA, USA
| | - Amit Meller
- Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
- Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
| | - Chirlmin Joo
- Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
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17
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Wang C, Liu M, Wang Z, Li S, Deng Y, He N. Point-of-care diagnostics for infectious diseases: From methods to devices. NANO TODAY 2021; 37:101092. [PMID: 33584847 PMCID: PMC7864790 DOI: 10.1016/j.nantod.2021.101092] [Citation(s) in RCA: 267] [Impact Index Per Article: 66.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 01/22/2021] [Accepted: 01/23/2021] [Indexed: 05/04/2023]
Abstract
The current widespread of COVID-19 all over the world, which is caused by SARS-CoV-2 virus, has again emphasized the importance of development of point-of-care (POC) diagnostics for timely prevention and control of the pandemic. Compared with labor- and time-consuming traditional diagnostic methods, POC diagnostics exhibit several advantages such as faster diagnostic speed, better sensitivity and specificity, lower cost, higher efficiency and ability of on-site detection. To achieve POC diagnostics, developing POC detection methods and correlated POC devices is the key and should be given top priority. The fast development of microfluidics, micro electro-mechanical systems (MEMS) technology, nanotechnology and materials science, have benefited the production of a series of portable, miniaturized, low cost and highly integrated POC devices for POC diagnostics of various infectious diseases. In this review, various POC detection methods for the diagnosis of infectious diseases, including electrochemical biosensors, fluorescence biosensors, surface-enhanced Raman scattering (SERS)-based biosensors, colorimetric biosensors, chemiluminiscence biosensors, surface plasmon resonance (SPR)-based biosensors, and magnetic biosensors, were first summarized. Then, recent progresses in the development of POC devices including lab-on-a-chip (LOC) devices, lab-on-a-disc (LOAD) devices, microfluidic paper-based analytical devices (μPADs), lateral flow devices, miniaturized PCR devices, and isothermal nucleic acid amplification (INAA) devices, were systematically discussed. Finally, the challenges and future perspectives for the design and development of POC detection methods and correlated devices were presented. The ultimate goal of this review is to provide new insights and directions for the future development of POC diagnostics for the management of infectious diseases and contribute to the prevention and control of infectious pandemics like COVID-19.
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Affiliation(s)
- Chao Wang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China
- Department of Biomedical Engineering, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, Jiangsu, PR China
| | - Mei Liu
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China
| | - Zhifei Wang
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China
| | - Song Li
- Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou 412007, PR China
| | - Yan Deng
- Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou 412007, PR China
| | - Nongyue He
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China
- Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou 412007, PR China
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18
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Spitzberg JD, van Kooten XF, Bercovici M, Meller A. Microfluidic device for coupling isotachophoretic sample focusing with nanopore single-molecule sensing. NANOSCALE 2020; 12:17805-17811. [PMID: 32820758 DOI: 10.1039/d0nr05000h] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Solid-state nanopores (NPs) are label-free single-molecule sensors, capable of performing highly sensitive assays from a small number of biomolecule translocation events. However, single-molecule sensing is challenging at extremely low analyte concentrations due to the limited flux of analytes to the sensing volume. This leads to a low event rate and increases the overall assay time. In this work, we present a method to enhance the event rate at low analyte concentrations by using isotachophoresis (ITP) to focus and deliver analytes to a nanopore sensor. Central to this method is a device capable of performing ITP focusing directly on a solid-state NP chip, while preventing the focusing electric field from damaging the nanopore membrane. We discuss considerations and trade-offs related to the design of the focusing channel, the ITP electrolyte system and electrical decoupling between the focusing and sensing modes. Finally, we demonstrate an integrated device wherein the concentration enhancement due to ITP focusing leads to an increase in event rate of >300-fold in the ITP-NP device as compared to the NP-only case.
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Affiliation(s)
- Joshua D Spitzberg
- Department of Biomedical Engineering, The Technion - Israel Institute of Technology, Haifa, 32000 Israel.
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19
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Fu J, Wu L, Qiao Y, Tu J, Lu Z. Microfluidic Systems Applied in Solid-State Nanopore Sensors. MICROMACHINES 2020; 11:mi11030332. [PMID: 32210148 PMCID: PMC7142662 DOI: 10.3390/mi11030332] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/08/2020] [Accepted: 03/20/2020] [Indexed: 01/04/2023]
Abstract
Microfluidic system, as a kind of miniature integrated operating platform, has been applied to solid-state nanopore sensors after many years of experimental study. In the process of introducing microfluidic into solid-state nanopore sensors, many novel device structures are designed due to the abundance of analytes and the diversity of detection methods. Here we review the fundamental setup of nanopore-based microfluidic systems and the developments and advancements that have been taking place in the field. The microfluidic systems with a multichannel strategy to elevate the throughput and efficiency of nanopore sensors are then presented. Multifunctional detection represented by optical-electrical detection, which is realized by microfluidic integration, is also described. A high integration microfluidic system with nanopore is further discussed, which shows the prototype of commercialization.
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Affiliation(s)
| | | | | | - Jing Tu
- Correspondence: (J.T.); (Z.L.); Tel.: +86-25-8379-2396 (J.T.); +86-25-8379-3779 (Z.L.)
| | - Zuhong Lu
- Correspondence: (J.T.); (Z.L.); Tel.: +86-25-8379-2396 (J.T.); +86-25-8379-3779 (Z.L.)
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20
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Zrehen A, Huttner D, Meller A. On-Chip Stretching, Sorting, and Electro-Optical Nanopore Sensing of Ultralong Human Genomic DNA. ACS NANO 2019; 13:14388-14398. [PMID: 31756076 PMCID: PMC6933818 DOI: 10.1021/acsnano.9b07873] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 11/22/2019] [Indexed: 05/22/2023]
Abstract
Solid-state nanopore sensing of ultralong genomic DNA molecules has remained challenging, as the DNA must be controllably delivered by its leading end for efficient entry into the nanopore. Herein, we introduce a nanopore sensor device designed for electro-optical detection and sorting of ultralong (300+ kilobase pair) genomic DNA. The fluidic device, fabricated in-silicon and anodically bonded to glass, uses pressure-induced flow and an embedded pillar array for controllable DNA stretching and delivery. Extremely low concentrations (50 fM) and sample volumes (∼1 μL) of DNA can be processed. The low height profile of the device permits high numerical aperture, high magnification imaging of DNA molecules, which remain in focus over extended distances. We demonstrate selective DNA sorting based on sequence-specific nick translation labeling and imaging at high camera frame rates. Nanopores are fabricated directly in the assembled device by laser etching. We show that uncoiling and stretching of the ultralong DNA molecules permits efficient nanopore capture and threading, which is simultaneously and synchronously imaged and electrically measured. Furthermore, our technique provides key insights into the translocation behavior of ultralong DNA and promotes the development of all-in-one micro/nanofluidic platforms for nanopore sensing of biomolecules.
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Affiliation(s)
- Adam Zrehen
- Department
of Biomedical Engineering, Technion −
IIT, Haifa 32000, Israel
| | - Diana Huttner
- Department
of Biomedical Engineering, Technion −
IIT, Haifa 32000, Israel
| | - Amit Meller
- Department
of Biomedical Engineering, Technion −
IIT, Haifa 32000, Israel
- Russell
Berrie Nanotechnology Institute, Technion
− IIT, Haifa 32000, Israel
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21
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Nouri R, Tang Z, Guan W. Calibration-Free Nanopore Digital Counting of Single Molecules. Anal Chem 2019; 91:11178-11184. [DOI: 10.1021/acs.analchem.9b01924] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Reza Nouri
- Department of Electrical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, United States
| | - Zifan Tang
- Department of Electrical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, United States
| | - Weihua Guan
- Department of Electrical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, United States
- Department of Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, United States
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