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Sensing of single DNA and proteins by surface charge modification of nanopores and micro chip fabrication
Nanopores (NPs) are fundamental to life as they enable the regulation of cells by allowing passage of only those objects with the appropriate physical properties. Here we'll manipulate the surface charge of artificial silicon based NPs in order to specifically sense biomolecules like DNA or proteins
Keywords: Sensing of DNA, protein and other biomolecules; surface charge; nanopore; biosensor; bioelectronics; micro-/ nano-fabrication; bionanotechnology; nanoparticles
Localized detection of ions and biomolecules is of paramount importance in understanding the physics of life at cellular and molecular scales. For example, a large number of biological processes in living cells are regulated and mediated by localized membrane transport.[1] Trafficking of macromolecules (such as proteins, RNA and DNA) and ions routed through the cell membrane determine the interaction of cells with each other, their environment and immunological response.[2] Any dysfunction of these trafficking routes causes severe problems leading to a variety of diseases, such as cancer, cardiac arrhythmias and epilepsies.[3] To understand the underlying biological mechanism of cell signalling, it is essential to identify and characterize transmembrane pathways at single-cell level.[4]
The rapid progress in nanopore sensing allows for the detection of individual nano-sized objects or biomolecules[5]. However, the specificity to single biomolecules and single amino or nucleic acids is still a major challenge in nanopore sensing. An improved specificity can be achieved by specific interaction of pore and analyte, e.g. by manipulation of the pores’ surface charge. The scope of this project will be to study the surface charge effect on a nanopore which will be achieved by the application of electrodes and/or the chemical functionalization of the pore.
The student will have the opportunity to work independently in the laboratories and cleanroom which are available at the Laboratory for Biosensors and Bioelectronics (LBB). The chip will allow for the confinement and electro-chemical detection of single biomolecules. Furthermore, the student will get to know the FluidFM [6], which has been developed at the LBB in order to conduct electrochemical DNA and protein sensing experiments.
**LITERATURE**
[1] B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter, Molecular biology of the cell, 4th ed. New York: Garland Science, 2002.
[2] P. Kollmannsberger, C. M. Bidan, J. W. C. Dunlop, P. Fratzl, and V. Vogel, “Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts,” Sci. Adv., vol. 4, no. 1, p. eaao4881, 2018.
[3] W. A. Catterall, “From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels,” Neuron, vol. 26, no. 1, pp. 13–25, 2000.
[4] B. Hille, Ion channels of excitable membranes, vol. 507. Sinauer Sunderland, MA, 2001.
[5] K. Lee et al., “Recent Progress in Solid-State Nanopores,” Adv. Mater., vol. 1704680, pp. 1–28, 2018.
[6] A. A. Meister et al., “FluidFM: Combining Atomic Force Microscopy and Nano uidics in a Universal Liquid Delivery System for Single Cell Applications and Beyond,” Nano Lett., vol. 9, no. 6, pp. 2501–7, 2009.
Localized detection of ions and biomolecules is of paramount importance in understanding the physics of life at cellular and molecular scales. For example, a large number of biological processes in living cells are regulated and mediated by localized membrane transport.[1] Trafficking of macromolecules (such as proteins, RNA and DNA) and ions routed through the cell membrane determine the interaction of cells with each other, their environment and immunological response.[2] Any dysfunction of these trafficking routes causes severe problems leading to a variety of diseases, such as cancer, cardiac arrhythmias and epilepsies.[3] To understand the underlying biological mechanism of cell signalling, it is essential to identify and characterize transmembrane pathways at single-cell level.[4] The rapid progress in nanopore sensing allows for the detection of individual nano-sized objects or biomolecules[5]. However, the specificity to single biomolecules and single amino or nucleic acids is still a major challenge in nanopore sensing. An improved specificity can be achieved by specific interaction of pore and analyte, e.g. by manipulation of the pores’ surface charge. The scope of this project will be to study the surface charge effect on a nanopore which will be achieved by the application of electrodes and/or the chemical functionalization of the pore. The student will have the opportunity to work independently in the laboratories and cleanroom which are available at the Laboratory for Biosensors and Bioelectronics (LBB). The chip will allow for the confinement and electro-chemical detection of single biomolecules. Furthermore, the student will get to know the FluidFM [6], which has been developed at the LBB in order to conduct electrochemical DNA and protein sensing experiments.
**LITERATURE** [1] B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter, Molecular biology of the cell, 4th ed. New York: Garland Science, 2002. [2] P. Kollmannsberger, C. M. Bidan, J. W. C. Dunlop, P. Fratzl, and V. Vogel, “Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts,” Sci. Adv., vol. 4, no. 1, p. eaao4881, 2018. [3] W. A. Catterall, “From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels,” Neuron, vol. 26, no. 1, pp. 13–25, 2000. [4] B. Hille, Ion channels of excitable membranes, vol. 507. Sinauer Sunderland, MA, 2001. [5] K. Lee et al., “Recent Progress in Solid-State Nanopores,” Adv. Mater., vol. 1704680, pp. 1–28, 2018. [6] A. A. Meister et al., “FluidFM: Combining Atomic Force Microscopy and Nano uidics in a Universal Liquid Delivery System for Single Cell Applications and Beyond,” Nano Lett., vol. 9, no. 6, pp. 2501–7, 2009.
The goal of this project is to distinguish different biomolecules by modification of surface charges around a nanopore.
The goal of this project is to distinguish different biomolecules by modification of surface charges around a nanopore.
Til Schlotter
schlotter@biomed.ee.ethz.ch
Laboratory of Biosensors and Bioelectronics
ETH Zürich, Gloriastrasse 35 / ETZ F76
Til Schlotter schlotter@biomed.ee.ethz.ch Laboratory of Biosensors and Bioelectronics ETH Zürich, Gloriastrasse 35 / ETZ F76