Gel Filtration Pipette Tips With Dry Media for Stable Auto-Packing
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Solution Overview
Problem
Current methods for preparing size exclusion columns are time-consuming and laborious, and automation of gel filtration processes is difficult to achieve, leading to inefficiencies and potential contamination issues with existing pipette tips containing pre-swollen media.
Innovation Solution
A pipette tip with a filter at the distal end and dry size exclusion media, allowing solvent to be aspirated from the bottom for rapid swelling and reproducible packing, eliminating the need for centrifugation and reducing human interaction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If pre-swollen media are used in pipette tips, then gel filtration can be performed, but the packed gel is readily disrupted during shipping resulting in air pockets and channeling issues
Solution Approach 1:
The pipette tip contains dry size exclusion media in a relaxed state during manufacturing and shipping. The media is activated and swelled to its functional gel state only after receipt by the user, through preliminary action of adding swelling buffer. This prevents disruption during shipping while enabling gel filtration capability.
Solution Approach 2:
The media undergoes a parameter change from dry/relaxed state to swollen/gel state upon contact with buffer. This transformation occurs after shipping, maintaining stability during transport while achieving the necessary gel structure for filtration when needed.
2Manufacturing precision
If additional steps are required to ensure adequate gel packing such as centrifugation, then gel quality improves, but time consuming steps that have to be performed by a technician and not the RLH
Solution Approach 1:
The pipette tip design enables self-service gel formation. When buffer is added, the dry media automatically swells and packs into a homogeneous gel column without requiring external centrifugation or manual intervention. The system performs its own preparation, making it compatible with automated robotic liquid handling.
Solution Approach 2:
The mechanical centrifugation step is replaced by a chemical/swelling mechanism. The buffer-induced swelling of the media naturally packs the gel homogeneously without mechanical force, eliminating the need for centrifugation and enabling full automation.
3Reliability
If glycerol is used to maintain the wet bed of media, then adverse column function is prevented, but the user must remove glycerol prior to use which is time consuming and introduces contamination issues
Solution Approach 1:
The problematic glycerol preservative is extracted/removed from the system. Instead, the pipette tip contains dry media that swells upon buffer addition, eliminating the need for glycerol removal steps and associated contamination risks while maintaining column function.
Solution Approach 2:
The media transitions from a dry state (requiring glycerol preservation) to a swollen gel state upon buffer addition. This parameter change eliminates the need for glycerol-based preservation and allows direct use with buffer, saving time and preventing contamination.
4Reliability
If size exclusion media must be wetted with large amounts of aqueous solvent for multiple hours or days, then separation performance is achieved, but the process is time consuming
Solution Approach 1:
The media is prepared in a dry, space-efficient form during manufacturing. The preliminary swelling action is performed by the user quickly after receipt by adding buffer, rather than requiring prolonged pre-swelling during storage or shipping. This maintains separation performance while dramatically reducing time.
Solution Approach 2:
The media undergoes rapid parameter change from dry to swollen state upon buffer addition, achieving full separation performance in minutes rather than hours or days. This fast transition maintains the necessary pore structure for effective separation.
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
Facilitates rapid and reproducible gel formation without air pockets, enabling automated gel filtration processes with reduced time and contamination risks, improving laboratory throughput.
Implementation Method 1
the resins are first wetted with large amounts of an aqueous solvent, such as an aqueous buffer, for multiple hours or days. The wetted resin swells to provide specified pores, allowing for separation.
Implementation Method 2
the resins are first wetted with large amounts of an aqueous solvent
Implementation Method 3
Size-exclusion chromatography (SEC) is a chromatographic method in which molecules in solution are separated by their hydrodynamic volume and/or molecular weight using size exclusion media with varying porosities.
Implementation Method 4
size exclusion media with varying porosities
Implementation Method 5
A pipette tip with a filter at the distal end and dry size exclusion media
Data Source
Figure 1A~1B
Figure 2A~2C
Figure 2B
AI summary
A device for automated or manual group separations of complex biological mixtures and methods of use are described. The device is a gel filtration pipette tip having a size exclusion media therein and held in place by a filter at the distal end of the pipette tip and an optional removable or pierceable barrier at the proximal end of the pipette tip. The size exclusion media is wetted by aspirating a solvent from the bottom of the pipette tip and equilibrating the solvent with the size exclusion media. The solvent is then allowed to gravity drain from the pipette tip, allowing the size exclusion media to settle and reproducibly pack into a homogenous gel. Gel filtration separations can then be performed with the gelled size exclusion media.