Systems and methods for controlling temperature of small volumes
Inventors
Kasianowicz, John J. • Reiner, Joseph E. • Balijepalli, Arvind K. • Robertson, Joseph W. • Burden, Daniel L. • Burden, Lisa
Assignees
National Institute of Standards and Technology NIST
Publication Number
US-9500610-B2
Publication Date
2016-11-22
Expiration Date
2033-11-06
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Abstract
Systems and methods for controlling the temperature of small volumes such as yoctoliter volumes, are described. The systems include one or more plasmonic nanostructures attached at or near a nanopore. Upon excitation of the plasmonic nanostructures, such as for example by exposure to laser light, the nanoparticles are rapidly heated thereby causing a change in the ionic conductance along the nanopore. The temperature change is determined from the ionic conductance. These temperature changes can be used to control rapid thermodynamic changes in molecular analytes as they interact with the nanopore.
Core Innovation
The invention provides systems and methods for controlling and measuring the temperature of small volumes, such as yoctoliter volumes, using plasmonic nanostructures attached at or near nanopores. The systems include a substrate with a nanopore, plasmonic structures disposed proximate to the nanopore, an ionic conducting solution bathing these structures, a light source to excite the plasmonic structures, and an ionic current measuring assembly. Upon excitation, the plasmonic nanostructures rapidly heat the volume, causing changes in ionic conductance along the nanopore, from which the temperature change is determined in real-time.
The problem addressed is the difficulty and drawbacks in prior temperature jump (T-jump) methods to rapidly perturb small volumes, particularly at the single molecule scale inside nanopores. Previous laser-based techniques require post processing to estimate temperature and are limited to single-pulse experiments with relaxation to room temperature, lacking the ability to precisely control complex temporal temperature profiles at very small volumes. There is a need for a highly localized heat source and a method to measure temperature in exceptionally small fluid volumes near or within nanopores.
The present subject matter solves these problems by using plasmonic metallic nanoparticles attached near or to the nanopore that can be optically excited to produce rapid and localized heating. This heating effect is monitored by measuring changes in ionic conductance of the nanopore, providing a direct electrical readout of the local temperature without the need for post-processing. This capability allows real-time control and measurement of temperature changes within the nanoscale sensing volume, enabling single molecule thermodynamic and kinetic analysis with high temporal resolution.
Claims Coverage
The patent includes multiple independent claims covering both a system and methods related to temperature measurement and control at nanopores using plasmonic structures. Three independent claims specifically detail the system and methods involved.
System for measuring temperature at a nanopore
A system comprising a substrate defining a surface and at least one nanopore; a plasmonic structure disposed proximate the nanopore; an ionic conducting solution bathing the nanopore and plasmonic structure; a light source capable of exciting the plasmonic structure; and an ionic current measuring assembly configured to measure changes in ionic conductance near the nanopore. Changes in ionic conductance upon excitation are used to determine temperature or temperature changes at the nanopore.
Method for measuring temperature at a nanopore
A method comprising providing a plasmonic structure, affixing it proximate the nanopore, emitting light of sufficient intensity and wavelength to excite the plasmonic structure inducing a temperature change, and measuring changes in ionic conductance proximate the nanopore to determine temperature or temperature changes.
Method for analyzing polymers using temperature control at a nanopore
A method comprising providing plasmonic nanostructures, providing a surface with a nanopore, affixing the nanostructures proximate the nanopore, disposing a polymer in the nanopore, and exciting the nanostructures with light to induce temperature changes within the nanopore. The temperature change is used to analyze the polymer disposed in the nanopore.
The independent claims collectively cover systems and methods employing plasmonic nanostructures attached near nanopores and excited by light to induce localized heating, with temperature changes detected via ionic conductance measurements. These features enable precise temperature control and measurement in nanoscale volumes and facilitate single molecule polymer analysis.
Stated Advantages
Provides a direct electrical measurement of temperature changes adjacent to the nanopore in real-time without the need for post-processing data.
Enables rapid, highly localized temperature control at the yoctoliter scale compatible with single molecule sensing volumes.
Allows precise control of temperature profiles over time, beyond single-pulse techniques, improving the temporal resolution of thermodynamic and kinetic studies.
Improves sensor systems and force measurements based on single nanopores by providing temperature as a controllable variable during single molecule analysis.
Documented Applications
Measurement and control of temperature in small fluid volumes at nanopores for single molecule thermodynamics and kinetics.
Analyzing polymers, such as poly(ethylene glycol), within a nanopore by assessment of temperature-dependent changes in ionic conductance.
Studying rapid thermodynamic changes and structural dynamics of molecular analytes interacting with nanopores.
Using temperature changes to discriminate between different polymer conformations and molecular species by modulating capture rates and residence times in nanopores.
Single molecule sensing and analysis, including folding/unfolding of proteins and nucleic acids, by combining nanopore sensors with plasmonic heating.
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