Droplet Sequencing Device Substrate Printing Fluorescence Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for sequencing nucleic acids using microdroplets are inefficient for analyzing nucleic acid fragments with significant nucleotide length, as they require dispersion in an immiscible carrier medium and lack suitable apparatus for precise droplet handling and fluorescence-based identification.
Innovation Solution
A droplet sequencing apparatus that prints droplets directly onto a planar substrate with droplet-receiving locations, using a printer head with nozzle groups to dispense single nucleotides and oligonucleotide probes, and employs fluorescence spectroscopy for identification, allowing for precise handling and analysis of long nucleic acid fragments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If droplets are dispersed in an immiscible carrier medium for sequencing, then droplet manipulation is enabled, but the method becomes inefficient for analyzing nucleic acid fragments with significant nucleotide length
Solution Approach 1:
The invention extracts the droplets from the immiscible carrier medium and deposits them directly onto a solid substrate. This removal of the carrier medium eliminates the limitations it imposes on analyzing long nucleic acid fragments while preserving the droplet-based manipulation advantages.
Solution Approach 2:
The solid substrate acts as an intermediary between the droplet generation system and the detection system. It provides a stable platform that supports droplet containment and enables fluorescence detection without requiring the droplets to remain suspended in an immiscible carrier medium.
2Manufacturing precision
If a printer head with multiple nozzle groups is used to dispense droplets, then precise droplet placement is achieved, but device complexity increases
Solution Approach 1:
The printer head is segmented into multiple nozzle groups, each responsible for dispensing specific types of droplets (e.g., nucleic acid-containing droplets, probe droplets, wash droplets). This segmentation enables precise control over droplet composition and placement while organizing the complexity into manageable functional units.
Solution Approach 2:
The invention transitions from single-dimensional droplet dispensing to multi-dimensional control by arranging nozzle groups in spatial configurations that enable precise two-dimensional addressing of droplet-receiving locations on the substrate, adding spatial organization to manage system complexity.
3Adaptability or versatility
If droplets are printed directly onto a substrate, then handling of long nucleic acid fragments is improved, but the system requires new apparatus not previously used in sequencing
Solution Approach 1:
The solid substrate serves multiple functions: it acts as a support structure for droplets, a platform for fluorescence detection, and a means for organizing and addressing individual nucleic acid fragments. This multi-functionality reduces the need for separate specialized components.
Solution Approach 2:
The substrate-based droplet containment system enables self-aligned droplet placement and stable positioning without requiring active control mechanisms. The physical structure of the substrate provides inherent guidance and stabilization, reducing the complexity of control systems needed.
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
Enables effective sequencing of nucleic acid fragments exceeding 100 nucleotides by enhancing droplet formation and fluorescence detection, improving the efficiency and accuracy of nucleotide identification on a substrate with optimized droplet-receiving locations and illumination.
Implementation Method 1
at least one source of incident electromagnetic radiation adapted to illuminate the droplet-receiving locations and at least one photodetector adapted to detect fluorescence radiation emitted by each droplet-receiving location after illumination
Data Source
Figure 1
Figure 2A~3
Figure 4~5
AI summary
An apparatus for sequencing a nucleic acid by printing droplets at least some of which contain single nucleotides derived from the nucleic acid is provided. It is characterised by comprising; • a planar substrate having a face with droplet-receiving locations arranged in at least one track parallel to a first axis defining the substrate; · a printer head comprising a plurality of droplet-dispensing nozzle groups juxtaposed above the droplet-receiving locations so that each nozzle group can in turn dispense a droplet into the droplet-receiving locations; • a means for stepping the printer head along the first axis relative to the droplet-receiving locations; · a nucleotide-generating site upstream of the printer head by means of which an ordered stream of single nucleotides is created from the nucleic acid and delivered to a first droplet-dispensing nozzle group; • at least one source of incident electromagnetic radiation adapted to illuminate the droplet-receiving locations and · at least one photodetector to detect adapted to detect fluorescence radiation emitted by each droplet-receiving location after illumination.