In the last few years, surface charge density modulation has also been suggested to slow down translocation events 28, 29, 30, 31, 32, 33, mostly by building nanopores with dielectric materials like Al 2O 3 29, 32, 34, 35 and HfO 2 30, or by exploring optoelectronic control of surface charge 33. Multiple approaches have been proposed to slow down the translocation events 20, which involve either modifying the properties (mostly viscosity) of the electrolyte 10, 21, 22, incorporating optical (or magnetic) traps or tweezers 20, 23, 24, or using protein tags to slow down the motion of the smaller molecules 25, 26, 27. An additional mechanism to dramatically reduce (by orders of magnitude) and control the fast electrophoretic velocity of molecules is therefore necessary to realize sensitive and selective solid-state nanopore sensors for short nucleic acids, and other small biomolecules 13 and sequencing platforms 2, 19. For the proposed sequencing applications by quantum tunneling, speed control is also a key issue for realizing practical quantum sequencers 9. This limitation hence prevents accurate profiling of promising cancer biomarkers like proteins, short mRNA fragments, and microRNAs (19–22 nt) by solid-state nanopores 13, 17, 18. High signal bandwidth, however, also strongly amplifies thermal noise in the current recordings this noise makes the signal resistive pulses become undetectable 16. At these high velocities, short nucleic acids (1 MHz) is needed to fully resolve the resistive pulses 14, 15. Typical electrophoretic velocities of nucleic acids across solid-state nanopores are 10–1000 ns per base 1. The high fields are due to the nanoscale pore dimensions necessary for resistive current signals above thermal noise, and the minimum bias voltage (20–60 mV) 10 necessary to overcome barriers due to conformation entropy, electrostatic repulsion, and electro-osmotic flow 11, 12. However, developing solid-state nanopore sensors capable of complete characterization of the translocating biomolecules has been challenging 1, 7, 9, primarily because of the fast electrophoretic translocation by highly focused electric fields at the pore. They facilitate integration with compact electronic/optical sensor modalities and allow higher throughput than their protein counterparts. Despite the progress that has been made with biological nanopores, solid-state nanopores with high stability and tunable pore diameters still offer several advantages. With the development of enzyme-based methods that ratchet polynucleotides through the pore, the first nanopore-sequencer has been realized using protein nanopores 3. The Achilles heel of nanopores has been the inability to control the motion of biomolecules during voltage-driven translocation through the pore 1, 3, 7, 8, 9. Solid-state and protein nanopores are an emerging class of single-molecule sensors for DNA sequencing 1, 2, 3, protein detection 1, 4, 5, and DNA–protein complex analyses 6.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |