Nanopore Flow Cell Fabrication via Silicon Substrate Extraction
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Solution Overview
Problem
The existing methods for manufacturing solid-state nanopore flow cells are inefficient due to long etch times and background noise issues, which increase costs and reduce detection resolution in biopolymer sequencing.
Innovation Solution
The method involves forming a multi-layer stack on a monocrystalline silicon substrate, transferring it to a glass substrate, and bonding it with a patterned surface to create a nanopore flow cell that eliminates monocrystalline silicon, thereby reducing background noise and shortening the etch time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If monocrystalline silicon substrate is used to support the membrane layer, then the nanopore flow cell can be fabricated using commercially available semiconductor device manufacturing equipment and methods, but charges accumulated in the substrate undesirably increase background noise in the current signal
Solution Approach 1:
The patent extracts the harmful monocrystalline silicon substrate from the final nanopore flow cell configuration. The membrane layer with nanopore is first formed on a silicon substrate using standard semiconductor fabrication equipment, then the silicon substrate is removed through sacrificial layer etching, leaving only the membrane layer suspended over the opening. This eliminates the charge accumulation problem while preserving the fabrication advantages.
Solution Approach 2:
The patent introduces a sacrificial layer (mediator) between the membrane layer and the silicon substrate. This sacrificial layer enables the membrane to be formed on the silicon substrate using standard equipment, then allows clean removal of the silicon substrate without damaging the membrane layer. The sacrificial layer mediates the transition from fabrication-supported configuration to final suspended configuration.
2Manufacturing precision
If the silicon substrate is exposed to silicon etchant for 9-13 hours to anisotropically etch through the thickness, then the opening is formed through the substrate, but the long etch time undesirably increases the cycle time and cost of forming the nanopore flow cell
Solution Approach 1:
The patent segments the substrate removal process into two distinct stages: first, standard photolithography and etching processes form openings through the silicon substrate to the membrane layer; second, a separate sacrificial layer removal process completely eliminates the silicon substrate. This segmentation allows the use of fast standard processes for the first stage while the second stage achieves complete substrate removal without requiring extended etching times.
Solution Approach 2:
The patent performs preliminary action by forming the sacrificial layer structure before the final substrate removal. The sacrificial layer is deposited and patterned in advance, creating a predefined removal path that enables complete substrate elimination through a controlled, time-efficient process rather than requiring prolonged direct etching of the substrate itself.
3Manufacturing precision
If the membrane layer is deposited onto the front side surface of the silicon substrate and the nanopore opening is formed through the membrane layer, then the nanopore can be precisely positioned, but the substrate thickness and material contribute to background noise
Solution Approach 1:
The patent extracts the silicon substrate from the final configuration after it has served its purpose during fabrication. The membrane layer with precisely positioned nanopore is formed on the silicon substrate using standard semiconductor processing, then the substrate is completely removed through the sacrificial layer process, leaving only the low-noise membrane layer in the final flow cell.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach results in a nanopore flow cell with reduced background noise and shorter fabrication time, enhancing the detection resolution and efficiency of biopolymer sequencing.
Implementation Method 1
a nanopore disposed through a membrane layer which separates two conductive fluid reservoirs
Implementation Method 2
As the biopolymer strand travels through the nanopore the different monomer units thereof, e.g., protein bases of a DNA or RNA strand, occlude different percentages of the nanopore thus changing the ionic current flow therethrough
Data Source
AI summary
Nanopore flow cells and methods of manufacturing thereof are provided herein. In one embodiment a method of forming a flow cell includes forming a multi-layer stack on a first substrate, e.g., a monocrystalline silicon substrate, before transferring the multi-layer stack to a second substrate, e.g., a glass substrate. Here, the multi-layer stack features a membrane layer, having a first opening formed therethrough, where the membrane layer is disposed on the first substrate, and a material layer is disposed on the membrane layer. The method further includes patterning the second substrate to form a second opening therein and bonding the patterned surface of the second substrate to a surface of the multi-layer stack. The method further includes thinning the first substrate and thinning the second substrate. Here, the second substrate is thinned to where the second opening is disposed therethrough. The method further includes removing the thinned first substrate and at least portions of the material layer to expose opposite surfaces of the membrane layer.