Integrating nanopore sensors within microfluidic channel arrays using controlled breakdown
Inventors
Tabard-Cossa, Vincent • Godin, Michel • TAHVILDARI, Radin • Beamish, Eric
Assignees
Publication Number
US-11198946-B2
Publication Date
2021-12-14
Expiration Date
2035-12-18
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Abstract
Nanopore arrays are fabricated by controlled breakdown in solid-state membranes integrated within polydimethylsiloxane (PDMS) microfluidic devices. This technique enables the scalable production of independently addressable nanopores. By confining the electric field within the microfluidic architecture, nanopore fabrication is precisely localized and electrical noise is significantly reduced during sensing.
Core Innovation
The invention presents an apparatus for fabricating one or more nanopores in a membrane integrated within microfluidic devices by controlled breakdown (CBD). This apparatus includes a first substrate with a common microchannel, a support structure or directly the membrane disposed on the first substrate, and a second substrate having one or more microfluidic channels positioned such that these channels are fluidly separated from the common microchannel by the membrane. Electrodes on opposing sides of the membrane apply an electric potential, creating a controlled electric field to induce dielectric breakdown in the membrane, thereby fabricating nanopores precisely localized within the microfluidic architecture.
The problem addressed by this invention stems from limitations in conventional nanopore fabrication methods, typically reliant on focused ion or electron beam drilling before integration into microfluidic devices. These methods require direct line-of-sight access, strict alignment, and are performed in vacuum conditions, which complicate integration, lower yield in array formation, introduce handling risks, and cause wetting issues when transferring to liquid environments. Furthermore, conventional methods may result in non-uniform electric fields and higher electrical noise due to exposed membrane areas.
This invention overcomes these integration and fabrication challenges by employing controlled dielectric breakdown in situ inside microfluidic channel arrays, enabling scalable, independently addressable nanopores with uniform electric fields. Microfluidic architectures and electrode arrangements are designed to localize the electric field and nanopore formation, minimizing exposed membrane areas and thus reducing electrical noise during sensing. Furthermore, the use of control valves and micro-vias within the microfluidic channels facilitates precise electrical and fluidic control, enabling array fabrication and large-scale integration.
Claims Coverage
The patent includes multiple independent claims covering various configurations of the apparatus for fabricating nanopores in membranes integrated with microfluidic channels using controlled electric fields. The claims focus on inventive features related to substrate structures, electrode arrangements, microfluidic channel designs, and control mechanisms.
Symmetric electric field generation across membrane
An apparatus wherein one or more microfluidic channels are routed adjacent to the membrane and configured to create an electric field across the membrane area that is symmetric with respect to a plane perpendicular to the membrane surfaces, enabling uniform nanopore fabrication by controlled dielectric breakdown.
Microfluidic channel loop configuration for field uniformity
The apparatus includes a first electrode disposed in the microfluidic channels where the channels form a loop downstream from the electrode and a section of the loop is routed over the membrane, shaping the electric field uniformly across the membrane.
Array of microfluidic channels with control valves
The apparatus comprises an array of microfluidic channels routed over the membrane, arranged symmetrically and substantially parallel adjacent to the membrane. Each channel includes at least two control valves disposed upstream and downstream of the membrane to control fluid or electric current flow through the channels.
Use of pneumatic elastomeric control valves
Control valves disposed in the microfluidic channels are defined as elastomeric polymers fluidly coupled to and actuated by a pneumatic source, enabling precise regulation of fluid flow and electric current in the channels during nanopore fabrication and sensing.
Current sensing and automatic voltage removal upon pore formation
The apparatus includes a current sensor electrically coupled to one of the electrodes to measure current between microfluidic channels and a common microchannel, with a controller that detects abrupt current increases indicating pore formation and automatically removes the applied electric potential.
Support structure hosting membrane with paired electrodes and uniform field
An apparatus comprising a first substrate with a common microchannel, a support structure hosting a membrane, a second substrate with microfluidic channels fluidly separated by the membrane, and a pair of electrodes arranged on opposing sides of the membrane. The microfluidic channels are routed adjacent to the membrane to create a symmetric electric field across its area.
The independent claims collectively cover apparatus configurations featuring substrates and support structures hosting the membrane, various microfluidic channel arrangements forming loops or arrays, use of elastomeric pneumatic control valves to regulate flow and electric current, electrode placement to create symmetric and uniform electric fields across the membrane, and current sensing mechanisms to detect nanopore formation and control voltage application.
Stated Advantages
Scalable production of independently addressable nanopores within microfluidic arrays.
Precise localization of nanopore fabrication by controlling electric field confinement within microfluidic architecture.
Significant reduction of electrical noise during sensing due to minimized exposed membrane area.
Improved integration with microfluidic devices overcoming alignment and vacuum fabrication limitations of traditional nanopore fabrication.
Capability to independently control electrical potential and fluid flow in microfluidic channels via pneumatic valves, facilitating large scale integration and improved device functionality.
Documented Applications
Label-free sensors for detecting single molecules such as DNA and proteins via ionic current modulation caused by biomolecule translocation through nanopores.
Single-molecule studies including DNA sequencing, protein detection and unfolding, single-molecule mass spectrometry, and force spectroscopy.
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