New generation of biosensors using nanopore extended Field Effect Transistors (NexFET)
Lead Research Organisation:
Imperial College London
Department Name: Metabolism, Digestion and Reproduction
Abstract
Biosensors are an integral and increasingly important part of modern life sciences and new developments in biosensor technologies are increasingly seeing their application in the process industry, security, environmental and biodefense application markets. We seek to address the limitations of current diagnostics and we propose the development of a radical new nanotechnology for high throughput electronic recognition of neurotransmitters. While there are some moves to develop nanotechnology approaches to biosensing, these have yet to make a mark and there remains an unmet need in the development of lab-on-chip biosensors that are affordable, integrated, fast, capable of multiplexed detection and monitoring, and crucially, highly selective which can detect trace levels of analyte in biological fluids. This proposal directly addresses these issues. This will be achieved by designing a new class of nanoscale FET sensors dubbed NexFET (nanopore extended Field Effect Transistor) that combine the advantages of nanopore single molecule sensors, FET's and recognition chemistry.
EPSRC's strategy states that it wishes to encourage new ways of thinking, develop new tools and stimulate further investigation in bioscience, medicine and environmental sciences within UK industry and other parts of government such as the NHS. A wide array of important biological and clinical problems exist that could be addressed with such bionanosensors. These include the study of cell growth, differentiation, migration, viral entry, immune system function and signal transduction involved in aging, cardiomyopathy, neurodegeneration, and cancer. Most of these processes involve biologically relevant molecules in cells and their environments. Thus the generation of nanosensors to measure these biological molecules in real time with high sensitivity and accuracy is potentially extremely valuable. The proposal contributes towards the EPSRC areas of Analytical Science, Diagnostics and Healthcare Technologies, and especially in the context of development of novel tools, methods, and technologies in the physical and biological sciences. It will provide the basis for a novel, easy to use, robust and inexpensive sensor technology, for the detection of neurotransmitters and proteins in-vitro in biological fluids.
EPSRC's strategy states that it wishes to encourage new ways of thinking, develop new tools and stimulate further investigation in bioscience, medicine and environmental sciences within UK industry and other parts of government such as the NHS. A wide array of important biological and clinical problems exist that could be addressed with such bionanosensors. These include the study of cell growth, differentiation, migration, viral entry, immune system function and signal transduction involved in aging, cardiomyopathy, neurodegeneration, and cancer. Most of these processes involve biologically relevant molecules in cells and their environments. Thus the generation of nanosensors to measure these biological molecules in real time with high sensitivity and accuracy is potentially extremely valuable. The proposal contributes towards the EPSRC areas of Analytical Science, Diagnostics and Healthcare Technologies, and especially in the context of development of novel tools, methods, and technologies in the physical and biological sciences. It will provide the basis for a novel, easy to use, robust and inexpensive sensor technology, for the detection of neurotransmitters and proteins in-vitro in biological fluids.
Planned Impact
This project will deliver an unprecedented advance in single-molecule, label-free sensing that will contribute substantially to the UK's global leadership in this area. The major outputs will be (i) a step-change in the development of new analytical and biophysical tools and (ii) interdisciplinary training for early-career researchers. (iii) This proposal also contributes to the current EPSRC Strategic Research Priority of Technology development for the biosciences. We anticipate that this will benefit policymakers, funding bodies and academic institutions by providing clear evidence of the value of interdisciplinary research for the future of UK science.
This proposal will lead to direct impact in a number of different areas:
Communications and engagement. All parties have strong commitments to knowledge exchange. The results of these studies will be published in top journals, after filing of any patents to protect the IP. In particular, we will present at biophysical, scanning probe and also medical meetings to ensure that those working in this area are aware of these advances in the field.
Academic Collaborations: the applicants on this grant all have numerous academic collaborators both within our institutions and worldwide, who can both provide input into and benefit from this research. Additionally, the radical nature of this research proposal provides an opportunity to seek new collaborations and industrial partners. A collaboration has recently been established with Prof David Dexter (Division of Brain Science, ICL) and he has agreed to contribute his expertise and clinical samples. He has 30 years of experience in the field of understanding the pathological mechanisms involved in the development of PD and the development of novel therapeutics through in-vitro and in-vivo animal models and clinical trials. In 2002 David set up the internationally renowned Parkinson's UK Tissue Bank where clinical samples (both brain and CSF). Other collaborations will be established with groups that have interests in nanoscale sensors for clinical applications (e.g. Prof Minjun Kim, Drexel University, and Prof Jaebum Choo, Hanyang University).
Industrial Collaborations: the radical nature of this research proposal provides new opportunities to develop both existing and potentially new collaborations with industrial partners. Related to this proposal, YK and DK have co-founded Ionscope Ltd which has and will result in efficient knowledge transfer especially related to objective 4 of this proposal. JBE and AI have strong links with Raith Technologies GmbH and Siemens Healthcare in Germany and Hitachi in Japan.
Transferable skills: the training provided to the researcher, on this project will increase the availability of highly skilled workers in the UK that will be an advantage in a knowledge-based economy. In addition, it will also lead to enhanced skills and knowledge for the leading academics that will inform their ability to progress the future development of this project.
This proposal will lead to direct impact in a number of different areas:
Communications and engagement. All parties have strong commitments to knowledge exchange. The results of these studies will be published in top journals, after filing of any patents to protect the IP. In particular, we will present at biophysical, scanning probe and also medical meetings to ensure that those working in this area are aware of these advances in the field.
Academic Collaborations: the applicants on this grant all have numerous academic collaborators both within our institutions and worldwide, who can both provide input into and benefit from this research. Additionally, the radical nature of this research proposal provides an opportunity to seek new collaborations and industrial partners. A collaboration has recently been established with Prof David Dexter (Division of Brain Science, ICL) and he has agreed to contribute his expertise and clinical samples. He has 30 years of experience in the field of understanding the pathological mechanisms involved in the development of PD and the development of novel therapeutics through in-vitro and in-vivo animal models and clinical trials. In 2002 David set up the internationally renowned Parkinson's UK Tissue Bank where clinical samples (both brain and CSF). Other collaborations will be established with groups that have interests in nanoscale sensors for clinical applications (e.g. Prof Minjun Kim, Drexel University, and Prof Jaebum Choo, Hanyang University).
Industrial Collaborations: the radical nature of this research proposal provides new opportunities to develop both existing and potentially new collaborations with industrial partners. Related to this proposal, YK and DK have co-founded Ionscope Ltd which has and will result in efficient knowledge transfer especially related to objective 4 of this proposal. JBE and AI have strong links with Raith Technologies GmbH and Siemens Healthcare in Germany and Hitachi in Japan.
Transferable skills: the training provided to the researcher, on this project will increase the availability of highly skilled workers in the UK that will be an advantage in a knowledge-based economy. In addition, it will also lead to enhanced skills and knowledge for the leading academics that will inform their ability to progress the future development of this project.
Organisations
Publications
Al Sulaiman D
(2021)
Length-Dependent, Single-Molecule Analysis of Short Double-Stranded DNA Fragments through Hydrogel-Filled Nanopores: A Potential Tool for Size Profiling Cell-Free DNA.
in ACS applied materials & interfaces
Al Sulaiman D
(2018)
Chemically Modified Hydrogel-Filled Nanopores: A Tunable Platform for Single-Molecule Sensing.
in Nano letters
Ali T
(2019)
Correlative SICM-FCM reveals changes in morphology and kinetics of endocytic pits induced by disease-associated mutations in dynamin.
in FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Alova A
(2020)
Prolonged oxygen depletion in microwounded cells of Chara corallina detected with novel oxygen nanosensors.
in Journal of experimental botany
Anand U
(2020)
CBD Effects on TRPV1 Signaling Pathways in Cultured DRG Neurons.
in Journal of pain research
Bednarska J
(2021)
Release of insulin granules by simultaneous, high-speed correlative SICM-FCM.
in Journal of microscopy
Bednarska J
(2020)
Rapid formation of human immunodeficiency virus-like particles.
in Proceedings of the National Academy of Sciences of the United States of America
Cadinu P
(2017)
Single Molecule Trapping and Sensing Using Dual Nanopores Separated by a Zeptoliter Nanobridge.
in Nano letters
Cadinu P
(2020)
Individually Addressable Multi-nanopores for Single-Molecule Targeted Operations.
in Nano letters
Cadinu P
(2018)
Double Barrel Nanopores as a New Tool for Controlling Single-Molecule Transport.
in Nano letters
Cai S
(2019)
Small molecule electro-optical binding assay using nanopores.
in Nature communications
Cai S
(2021)
Single-molecule amplification-free multiplexed detection of circulating microRNA cancer biomarkers from serum.
in Nature communications
Crick C
(2017)
Low-Noise Plasmonic Nanopore Biosensors for Single Molecule Detection at Elevated Temperatures
in ACS Photonics
Edwards C
(2021)
Follow Your Nose: A Key Clue to Understanding and Treating COVID-19.
in Frontiers in endocrinology
Erofeev A
(2018)
Novel method for rapid toxicity screening of magnetic nanoparticles
in Scientific Reports
Fried JP
(2021)
Understanding Electrical Conduction and Nanopore Formation During Controlled Breakdown.
in Small (Weinheim an der Bergstrasse, Germany)
Fried JP
(2021)
In situ solid-state nanopore fabrication.
in Chemical Society reviews
Gopal S
(2019)
Porous Silicon Nanoneedles Modulate Endocytosis to Deliver Biological Payloads.
in Advanced materials (Deerfield Beach, Fla.)
Ivanov AP
(2018)
Scissoring genes with light.
in Nature chemistry
Klenerman D
(2021)
Noncontact Nanoscale Imaging of Cells.
in Annual review of analytical chemistry (Palo Alto, Calif.)
Kolmogorov VS
(2021)
Mapping mechanical properties of living cells at nanoscale using intrinsic nanopipette-sample force interactions.
in Nanoscale
Kwan Z
(2023)
Microtubule-Mediated Regulation of ß 2 AR Translation and Function in Failing Hearts
in Circulation Research
Lauri A
(2017)
3D Confocal Raman Tomography to Probe Field Enhancements inside Supercluster Metamaterials
in ACS Photonics
Lin X
(2017)
Selective single molecule nanopore sensing of proteins using DNA aptamer-functionalised gold nanoparticles.
in Chemical science
Liu F
(2022)
Phycosphere pH of unicellular nano- and micro- phytoplankton cells and consequences for iron speciation.
in The ISME journal
Maynard SA
(2021)
IL-1ß mediated nanoscale surface clustering of integrin a5ß1 regulates the adhesion of mesenchymal stem cells.
in Scientific reports
Nadappuram BP
(2019)
Nanoscale tweezers for single-cell biopsies.
in Nature nanotechnology
Oh S
(2021)
Nanophotonic biosensors harnessing van der Waals materials
in Nature Communications
Peveler W
(2017)
Covalently Attached Antimicrobial Surfaces Using BODIPY: Improving Efficiency and Effectiveness
in ACS Applied Materials & Interfaces
Ren R
(2017)
Nanopore extended field-effect transistor for selective single-molecule biosensing.
in Nature communications
Ren R
(2020)
Selective Sensing of Proteins Using Aptamer Functionalized Nanopore Extended Field-Effect Transistors
in Small Methods
Ren R
(2021)
Single-Molecule Binding Assay Using Nanopores and Dimeric NP Conjugates.
in Advanced materials (Deerfield Beach, Fla.)
Savin N
(2023)
Scanning ion-conductance microscopy technique for studying the topography and mechanical properties of Candida parapsilosis yeast microorganisms.
in Biomaterials science
Swiatlowska P
(2020)
Short-term angiotensin II treatment regulates cardiac nanomechanics via microtubule modifications.
in Nanoscale
Sze JYY
(2017)
Single molecule multiplexed nanopore protein screening in human serum using aptamer modified DNA carriers.
in Nature communications
Takahashi Y
(2020)
High-Speed SICM for the Visualization of Nanoscale Dynamic Structural Changes in Hippocampal Neurons.
in Analytical chemistry
Takahashi Y
(2020)
High-Resolution Electrochemical Mapping of the Hydrogen Evolution Reaction on Transition-Metal Dichalcogenide Nanosheets.
in Angewandte Chemie (International ed. in English)
Tang L
(2021)
Combined quantum tunnelling and dielectrophoretic trapping for molecular analysis at ultra-low analyte concentrations.
in Nature communications
Vaneev AN
(2022)
In Vitro/In Vivo Electrochemical Detection of Pt(II) Species.
in Analytical chemistry
Vaneev AN
(2022)
Nano- and Microsensors for In Vivo Real-Time Electrochemical Analysis: Present and Future Perspectives.
in Nanomaterials (Basel, Switzerland)
Vaneev AN
(2020)
In Vitro and In Vivo Electrochemical Measurement of Reactive Oxygen Species After Treatment with Anticancer Drugs.
in Analytical chemistry
Vivekananda U
(2017)
Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization.
in Proceedings of the National Academy of Sciences of the United States of America
Wang X
(2020)
Correction: Single-molecule nanopore sensing of actin dynamics and drug binding.
in Chemical science
Wang X
(2019)
Single-molecule nanopore sensing of actin dynamics and drug binding.
in Chemical science
Xue L
(2018)
Gated Single-Molecule Transport in Double-Barreled Nanopores.
in ACS applied materials & interfaces
Xue L
(2020)
Solid-state nanopore sensors
in Nature Reviews Materials
Zhang Y
(2019)
High-resolution label-free 3D mapping of extracellular pH of single living cells.
in Nature communications
Zhou Y
(2018)
Nanoscale Imaging of Primary Cilia with Scanning Ion Conductance Microscopy
in Analytical Chemistry
Description | There has been a significant drive to deliver nanotechnological solutions to biosensing, yet there remains an unmet need in the development of biosensors that are affordable, integrated, fast, capable of multiplexed detection, and offer high selectivity for trace analyte detection in biological fluids. Herein, some of these challenges are addressed by designing a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry. We report on a polypyrrole functionalized nexFET, with controllable gate voltage that can be used to switch on/off, and slow down single-molecule DNA transport through a nanopore. This strategy enables higher molecular throughput, enhanced signal-to-noise, and even heightened selectivity via functionalization with an embedded receptor. This is shown for selective sensing of an anti-insulin antibody in the presence of its IgG isotype. |
Exploitation Route | Novel nano sensors |
Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
Title | Nanopore extended field-effect transistor for selective single-molecule biosensing |
Description | We designed a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry. This strategy enables higher molecular throughput, enhanced signal-to-noise, and even heightened selectivity via functionalization with an embedded receptor. |
Type Of Material | Biological samples |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | not yet |