Preheating Fluid Delivery Channels for Nucleic Acid Sequencing

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Solution Overview

Problem

Nucleic acid sequencing processes are hindered by temperature differences between reagent reservoirs and the heated flow cell, leading to base call errors, incomplete sequencing reactions, and inconsistent results due to reagents equilibrating over time, causing temperature gradients and side reactions.

Innovation Solution

An apparatus and method that include a stage to support a flow cell, a detector, fluid delivery channels connecting reservoirs to the flow cell, and heaters to preheat reagents before they reach the flow cell, ensuring consistent and efficient temperature regulation across the detection channel.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If reagents are stored in reservoirs at room temperature and then delivered to a heated flow cell, then the sequencing reaction can proceed at optimal temperature, but temperature gradients cause base call errors and incomplete sequencing reactions

Engineering Contradiction:
Improvesequencing accuracyVSAvoidtemperature gradient
Core Design Contradiction:
ReliabilityVSTemperature

Solution Approach 1:

The patent applies preliminary action by preheating reagents in the fluid delivery channels before they reach the flow cell. Heaters embedded in the fluidic pathways warm the reagents during transit, ensuring they arrive at the optimal temperature for the sequencing reaction. This eliminates temperature gradients and prevents base call errors caused by thermal shock to temperature-sensitive enzymes like polymerases.

Inventive Principle:
Principle #10Preliminary action

2Stability of the object's composition

If reagents are equilibrated over time to match flow cell temperature, then temperature consistency is improved, but sequencing time increases and productivity decreases

Engineering Contradiction:
Improvetemperature consistencyVSAvoidsequencing speed
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The system performs preliminary heating of reagents during their delivery through heated fluidic channels, eliminating the need for time-consuming equilibration periods. Reagents are warmed to the optimal temperature en route to the flow cell, maintaining temperature consistency while enabling rapid sequencing operations without compromising enzyme activity or reaction completeness.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The heated fluidic delivery system enables continuous operation by maintaining reagents at optimal temperature throughout the delivery process. This continuous thermal management eliminates interruptions for temperature equilibration, allowing the sequencing process to proceed without delays and maintaining high productivity while ensuring temperature consistency.

Inventive Principle:
Principle #20Continuity of useful action

3Productivity

If heated liquid reagent is transferred to detection channel, then sequencing reaction efficiency is improved, but reagent volume must be precisely controlled

Engineering Contradiction:
Improvesequencing efficiencyVSAvoidreagent volume
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent employs parameter changes by precisely controlling the temperature of reagents during delivery through heated fluidic channels. By maintaining optimal temperature throughout transit, the system maximizes reagent efficiency and reaction completeness. This thermal control ensures that minimal reagent volumes are required to achieve complete sequencing reactions, reducing waste while maintaining high productivity.

Inventive Principle:
Principle #35Parameter changes

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 reduces sequencing time, lowers costs, and minimizes reagent volume by maintaining optimal temperatures, reducing errors and inconsistencies in nucleic acid sequencing results.

Implementation Method 1

a first heater that transfers heat to the plurality of fluid delivery channels

Methodology Applied
Scientific EffectHeat transfer: Conduction (thermal)

Implementation Method 2

a second heater that transfers heat to the detection channel of the flow

Methodology Applied
Scientific EffectHeat transfer: Conduction (thermal)

Data Source

PatentUS12077815B2Temperature control for analysis of nucleic acids and other analytes
Publication Date: 2024.09.03 PACIFIC BIOSCIENCES OF CALIFORNIA INC
  • US12077815B2 patent drawing
  • US12077815B2 patent drawing
  • US12077815B2 patent drawing

AI summary

Provided herein and methods and apparatuses for sequencing nucleic acids. For example, provided is an analytical detection apparatus, including (a) a stage configured to support a flow cell; (b) a detector configured to observe a detection channel of the flow cell when the flow cell is supported by the stage; (c) a plurality of fluid delivery channels, wherein each of the fluid delivery channels fluidically connects a reservoir to the detection channel of the flow cell; and (d) a first heater configured to heat the plurality of fluid delivery channels.