Nanofluidic analytical devices and methods of using thereof
Inventors
Soper, Steven A. • McKinney, Collin J. • PODLAHA-MURPHY, Elizabeth • PARK, Sunggook
Assignees
Board Of Supervisors Of Lsu And A&m College • Univ Of N Carolina At Chapel Hill • Northeastern University Boston • University of Kansas • Clarkson University
Publication Number
US-12280374-B2
Publication Date
2025-04-22
Expiration Date
2039-07-15
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Abstract
Disclosed are nanofluidic analytical devices. The devices employ a sample processing region that includes a plurality of fluidically connected sample handling elements that, in combination, affect a physical change on a sample introduced into the sample processing region. This physical change can include, for example, purification of an analyte of interest present in the sample, concentration of an analyte of interest present in the sample, chemical modification (e.g., cleavage and/or chemical derivatization) of an analyte of interest present in the sample, or a combination thereof. The analytical devices further include a nanochannel comprising a plurality of in-plane nanopores in series fluidically coupled to the sample processing region. The in-plane nanopores can be used to detect and/or analyze analyte(s) present in the sample following processing by the sample processing region. These analytical devices can advantageously provide for the label-free detection of single molecules.
Core Innovation
The invention provides nanofluidic analytical devices that incorporate a sample processing region with two or more fluidically coupled sample handling elements defined by a substrate. These handling elements act together to apply a physical, biophysical, or chemical change on a sample introduced into the processing region, such as purification, concentration, or chemical modification (including enzymatic cleavage or derivatization) of analytes of interest. The processed sample is then fluidically directed into a nanochannel that contains a plurality of in-plane nanopores in series. These in-plane nanopores are used for the detection and/or analysis of analytes within the processed sample.
The patent addresses the problem with existing nanopore-based detection methodologies, which require extensive sample preparation before nanopore measurements can be made. The presented solution integrates nanopore-based detectors into a network of fluidic components, thereby allowing for greater control of single-molecule transport and detection. This integration provides label-free detection and analysis of single molecules, which meets analysis requirements in fields like genomics, proteomics, and medical diagnostics.
The nanochannel described in the device has an input and output end and includes at least a first and a second in-plane nanopore spaced apart along its length. The nanochannel and nanopores' dimensions and configuration can be specifically tailored for various analytical applications, including nucleic acid sequencing, protein and polypeptide identification, as well as nanoparticle characterization. The architecture supports the fabrication of devices with high throughput and minimal sample amounts, allowing for single-molecule analysis without the need for labels or additional detection reporters.
Claims Coverage
The patent includes one independent claim that covers the primary inventive features of the analytical device.
Analytical device with a sample processing region and fluidically coupled nanochannels containing in-plane nanopores
An analytical device comprising: - A sample processing region with two or more fluidically coupled sample handling elements defined by a substrate, wherein these elements together affect a physical change on a sample introduced into the region. - A first nanochannel formed in the substrate and fluidically coupled to the sample processing region, the first nanochannel having an input end, output end, a first nanopore near the input, and a second nanopore spaced apart near the output end. - A second nanochannel coupled orthogonally with the first nanochannel, where the second nanochannel also includes its own input end, output end, a third nanopore proximate to its input, and a fourth nanopore proximate to its output end. This configuration enables the combination of sample processing with multi-dimensional nanochannel-based detection and/or analysis using in-plane nanopores.
The claims focus on an analytical device that integrates a sample processing region with a nanochannel having at least two in-plane nanopores and further includes an orthogonally coupled nanochannel with its own nanopores. This device structure enables physical changes and high-precision analysis of samples using fluidic coupling and nanopore-based detection.
Stated Advantages
Allows for label-free detection of single molecules after sample processing.
Provides greater control over single-molecule transport and detection by integrating nanopore-based detectors with fluidic handling components.
Facilitates automation of the entire sample-processing pipeline for clinical sequencing.
Enables high-throughput analysis by permitting fabrication of many devices on a single substrate, reducing device cost and increasing sample processing capacity.
Permits precise tuning of nanochannel and nanopore dimensions to match desired analytical applications.
Reduces the need for extensive sample preparation before nanopore measurement.
Enables modular integration of pre-processing and enrichment steps directly on the device.
Enhances signal-to-noise ratio (SNR) and measurement accuracy with specialized electronics and multi-electrode configurations.
Documented Applications
Sequencing nucleic acids including DNA and RNA, with applications to double-stranded DNA, single-stranded DNA, methylated bases, damaged bases, nucleotide insertions, deletions, translocations, and mutations.
Identification of proteins and polypeptides by detecting and analyzing peptide fragments generated by proteolysis in the device.
Characterization, counting, sizing, and zeta potential determination of nanoparticles, including synthetic nanoparticles, viral capsids, and exosomes.
Isolation and analysis of specific analytes from biological samples, such as circulating tumor cells (CTCs) and cell free DNA (cfDNA) from blood.
Integration into high-throughput analytical systems by fabricating multiple devices on wafer-scale chips for parallel analysis.
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