High-Resolution Analysis Devices and Related Methods
AssigneeThe Trustees of the University of Pennsylvania
InventorsMarija Drndic, Meni Wanunu, Tali Dadosh
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Abstract
Disclosed are solid-state nanopore devices having pores of nanometer-scale thickness, which ultrathin (e.g., less than 10 nm thick) pores enable devices having improved resolution. Also provided are methods of fabricating such devices and of using such devices. The invention also provides nanometer-thick membranes and related methods of fabricating such membranes, which membranes are useful in high resolution microscopy applications. Further disclosed are devices for detection of analytes—including miRNA—that may be small in size and may also be present in only small quantities.
Claims20
A detection device, comprising:
- a first capture material configured to bind preferentially to a first molecule;
- a membrane having a thickness in the range of from about 20 nm to about 100 nm, and the membrane having a thinned region,
- the thinned region having a thickness in the range of from about 0.1 nm to about 20 nm, and
- a first pore extending through the thinned region,
- the first pore being in fluid communication with the capture material;
- and
- a detector configured to detect a signal related to passage of the first molecule through the first pore.
A method of detecting an analyte, comprising:
- contacting a sample to a first capture material that preferentially binds to a first analyte;
- eluting the first analyte from the capture material;
- translocating the first analyte through a first pore disposed in a thinned region of a membrane, the thinned region having a thickness in the range of from about 0.1 nm to about 20 nm;
- and
- detecting a signal related to the translocation of the molecule through the first pore.
A detection device, comprising:
- a first capture material that binds specifically to a first molecule;
- a first membrane having a thickness in the range of from about 5 nm to about 100 nm;
- and
- a second membrane disposed adjacent the first membrane,
- the second membrane having a thickness in the range of from about 2 nm to about 20 nm, and the second membrane having at least one pore extending therethrough,
- the pore having a cross-sectional dimension in the range of from about 1 nm to about 100 nm, and
- the first membrane having a cavity formed thereon, the cavity being in register with at least one pore of the second membrane,
- the first pore being in fluid communication with the first capture material;
- a device configured to apply a gradient across the pore;
- and
- a detector configured to detect a signal related to passage of a molecule through the first pore.
An analysis device, comprising:
- a membrane having a membrane thickness of from about 20 nm to about 1000 nm,
- the membrane having a thinned region thereon,
- the thinned region having a thickness of between about 1 nm and about 20 nm.
An analysis device, comprising:
- a first membrane having a thickness in the range of from about 5 nm to about 100 nm;
- and
- a second membrane disposed adjacent the first membrane,
- the second membrane having a thickness in the range of from about 2 nm to about 20 nm,
- the second membrane having at least one pore extending therethrough, the pore having a cross-sectional dimension in the range of from about 1 nm to about 100 nm.
A method, comprising:
- translocating a population of oligonucleotides through a nanopore having a cross-sectional dimension in the range of from about 1 nm to about 1000 nm formed in a membrane having a thickness in the range of from about 20 nm to about 1000 nm,
- collecting a plurality of signals related to the translocation of the population of oligonucleotides through the nanopore;
- and
- correlating the plurality of signals to the presence of methylated bases, hydroxymethylated bases, or both, present in the population of oligonucleotides.
Dependencies are inferred from the claim text.