Encapsulating Lyophilized Microspheres via Fluidized Bed Coating

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Solution Overview

Problem

Current sequencing technologies face challenges with the stability and handling of lyophilized microspheres due to sensitivity to environmental conditions, leading to issues like tribocharging, degradation during transport, and inefficiencies in sample preparation processes.

Innovation Solution

A method involving the generation of a fluidized bed of lyophilized microspheres with a coating formulation, applied using a spray nozzle, to encapsulate them, providing stability and reducing static charge, while maintaining low water content and controlled humidity, thereby enhancing handling and storage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If lyophilized microspheres are stored and transported in dry form, then ambient transport and storage are enabled, but the microspheres become sensitive to environmental conditions leading to tribocharging and degradation

Engineering Contradiction:
Improvetransport and storage convenienceVSAvoidmicrosphere stability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent applies prior cushioning by coating the lyophilized microspheres with a protective layer before transport and storage. This coating acts as a cushion against environmental stressors such as moisture and static charge, preventing tribocharging and degradation that would otherwise occur during ambient handling. The coating is applied in advance to protect the microspheres throughout the supply chain.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Solution Approach 2:

The patent employs flexible shells and thin films by using a coating formulation that forms a thin protective film around each microsphere. This film provides a barrier against environmental conditions while maintaining the microsphere's structural integrity. The coating is applied as a liquid formulation that dries to form a flexible, protective shell.

Inventive Principle:
Principle #30Flexible shells and thin films

2Ease of operation

If lyophilized microspheres are handled in dry environments, then ambient handling is possible, but static charge builds up causing dispensing and compounding difficulties

Engineering Contradiction:
Improvehandling convenienceVSAvoidstatic charge
Core Design Contradiction:
Ease of operationVSObject-generated harmful factors

Solution Approach 1:

The patent uses an intermediary approach by introducing a coating formulation that acts as a mediator between the microsphere surface and the environment. This coating reduces tribocharging by providing a surface that minimizes static charge generation during handling. The coating formulation includes components specifically selected to reduce static electricity buildup while allowing ambient handling.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Manufacturing precision

If multiple steps are used in sample preparation, then library preparation can be achieved, but the process becomes difficult, tedious, and inefficient

Engineering Contradiction:
Improvelibrary preparation qualityVSAvoidsample preparation efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent applies merging by combining multiple sample preparation steps into a single streamlined process. The coated microspheres are designed to perform multiple functions in one operation, reducing the number of separate steps required for library preparation. This integration maintains preparation quality while significantly improving efficiency by eliminating redundant operations.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent uses preliminary action by pre-coating the microspheres with the coating formulation before they are used in sample preparation. This pre-treatment ensures that the microspheres are ready for immediate use without requiring additional preparation steps during the library preparation process, thereby streamlining the workflow and improving overall efficiency.

Inventive Principle:
Principle #10Preliminary action

4Reliability

If wet reagents are used, then reagent stability is maintained, but freezing is required for storage and transport

Engineering Contradiction:
Improvereagent stabilityVSAvoidstorage and transport requirements
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent applies parameter changes by transforming the reagent state from wet to dry through lyophilization, and then applying a coating that preserves stability in the dry state. This changes the physical and chemical parameters of the reagent system, allowing storage at ambient temperature rather than requiring freezing, while maintaining reagent stability through the protective coating.

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

The encapsulation method improves the stability and handling of lyophilized microspheres, reducing tribocharging and degradation, and simplifies workflows by providing a more stable and efficient sample preparation process.

Implementation Method 1

generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel

Methodology Applied
Scientific EffectFluidization: Fluidisation

Implementation Method 2

The coating formulation is sprayed on the one or more lyophilised microspheres in the fluidized bed

Methodology Applied
Scientific EffectSpray deposition: Spray

Data Source

PatentUS20230348967A1Methods and systems for encapsulating lyophilised microspheres
Publication Date: 2023.11.02 ILLUMINA INC
  • US20230348967A1 patent drawing
  • US20230348967A1 patent drawing
  • US20230348967A1 patent drawing

AI summary

The present disclosure relates to a method, including providing one or more lyophilised microspheres in a mixing vessel at a first temperature and generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel, under conditions effective to encapsulate the one or more lyophilised microspheres with a coating formulation. In an example, the fluidized bed has a fluidization rate of between about 1 cubic meters per hour (m3/h) and about 30 m3/h. In another example, the fluidized bed has an environmental humidity of between about 10% and about 20%. In still another example, the coating formulation is applied at a spray rate of between about 1.5 grams per minute (g/min) and about 10 g/min. In yet another example, the coating formulation is applied at an atomizing rate of between about 0.5 bar and about 1.5 bar. In a further example, the fluidized bed is in a Wurster configuration, a top spray configuration, or a combination thereof. The present disclosure also relates to a system, including one or more lyophilised microspheres, a mixing vessel configured for holding the one or more lyophilised microspheres, a mixer for generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel at a location, and at least one spray nozzle configured to introduce a shell formulation into the mixing vessel at the location.