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Systems And Methods For Controlling Temperature Of Small Volumes

The equilibrium state of a chemical or biological system is determined by many physical and chemical variables. Changes in one or more of these variables drive the system into a new steady state. Measurement of relaxation times provides information about the underlying properties of the system. Historically, the ability to perturb large ensembles of molecules from equilibrium led to major advances in understanding reaction mechanisms in chemistry and biology. Today, the behavior of molecules along reaction pathways and the inter- and intra-molecular dynamics are best obtained using single molecule measurement techniques.

A less explored methodology involves isolation of the thermodynamic perturbation (e.g., temperature, pressure, chemical binding) on a single molecule and the subsequent observation of that same molecule. The methodology uses plasmonic nanostructures, a nanopore, and laser light for controlling and/or measuring temperature of small volumes to analyze polymers or other molecules by coupling plasmonic structures (e.g., metallic nanoparticles or other nanostructures) adjacent to a single nanometer-scale protein ion channel or nanopore. Visible laser light incident on the nanoparticles causes a rapid and large increase of the solution temperature, which is measured by the change in the nanopore ionic conductance. The temperature shift affects the ability of individual molecules to enter into and interact with the nanopore.

The difficulties and drawbacks associated with previously known practices are addressed using this methodology. It represents the ultimate sensitivity in reaction measurements because the methodology isolates the internal degrees of freedom of a single molecule. It resolves the issue of measuring “immeasurably fast” diffusion-controlled reactions and enables precise control, measurement, and use of rapid temperature changes of fluid volumes that are commensurate with the size of single molecules. Additionally, it can significantly improve sensor systems and force measurements based on single nanopores, thereby enabling a method for single molecule thermodynamics and single molecule kinetics. Finally this regime can be modified in such a way to measure temperature at a nanopore; analyze polymers; and calculate the temperature of polymers without departing from producing ultimate sensitivities in reaction measurement.

Information on the figure below: A schematic illustration of an approximate yoctoliter volume heating and measurement system (10)
Forty nanometer diameter gold nanoparticles (20) are attached to a single nanopore or protein ion channel (30) formed by a genetically engineered version of the pore-forming toxin aHL, via (30) base pair duplex DNA.
Tethers are depicted as (40). Continuous wave green laser light (532 nm) incident on the nanoparticles is strongly absorbed at or near the surface plasmon resonance, and raises their temperature. The temperature increase is determined from the change in the nanopore's ionic conductance.

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.

Benefits: 

It resolves the issue of measuring “immeasurably fast” diffusion-controlled reactions and enables precise control, measurement, and use of rapid temperature changes of fluid volumes that are commensurate with the size of single molecules.

applications: 

Imaging and Cancer Therapies

Inventors: 

Kasianowicz, J; Robertson, J; Reiner, W.; Burden, J; Burden, L.; Balijepalli, A

Patent Number: 
9,921,174
Technology Type(s): 
Thermodynamics, Laser Applications, Analytical Chemistry, Atomic Physics, Biochemical Science, Chemical Physics, Chemical Sciences, Nanotechnology, Polymers, Physical and Chemical Properties
Internal Laboratory Ref #: 
12-034D
Patent Issue Date: 
March 20, 2018
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