Tip-on-tip filter pipette tip for automated solid phase extraction
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Solution Overview
Problem
Current automation methods for protein precipitation and solid phase extraction in biological and chemical samples are complex, costly, and time-consuming, often requiring additional robotic accessories and leading to issues like clogging, contamination, and ion suppression due to the need for centrifugation, vacuum manifolds, and magnetic fields.
Innovation Solution
The use of modified robotic pipette tips in a 'tip-on-tip' format, where a filter pipette tip with optional substrates and sorbents forms an air-tight seal with a standard or wide bore pipette tip, allowing for automated filtration and extraction without additional accessories, reducing human intervention and processing time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional protein precipitation and separation methods (centrifugation, vacuum manifolds, magnetic fields) are used, then analyte recovery is achieved, but device complexity and processing time increase significantly
Solution Approach 1:
The patent combines filtration and solid phase extraction into a single integrated filter tip assembly that can be used with standard robotic liquid handlers. The filter tip incorporates both the filtration membrane and the sorbent material in one component, eliminating the need for separate centrifugation, vacuum manifold, or magnetic field systems. This merging of functions reduces device complexity while maintaining analyte recovery through the combined filtration-extraction process.
Solution Approach 2:
The filter tip is designed to perform multiple functions: filtration of precipitated proteins, solid phase extraction of analytes, and compatibility with standard robotic liquid handlers. This multi-functional design eliminates the need for specialized robotic accessories, making the system universally applicable to existing laboratory automation infrastructure while maintaining reliable analyte recovery.
2Productivity
If in-well precipitation with shaking is used, then throughput increases, but sample contamination and clogging occur
Solution Approach 1:
The patent segments the precipitation and filtration processes into separate steps. First, protein precipitation is performed in the well plate without shaking. Then, the supernatant is transferred to filter tips for filtration. This segmentation prevents clogging by avoiding shaking of precipitated samples and eliminates contamination risks associated with in-well shaking, while maintaining high throughput through automated liquid handling.
Solution Approach 2:
The filter tip acts as an intermediary device between the precipitation well and the analysis instrument. It receives the precipitated sample, performs filtration to remove proteins and particulates, and delivers a clean filtrate to the analysis system. This intermediary step prevents clogging of downstream instruments and eliminates contamination while maintaining high throughput through automated operation.
3Extent of automation
If automated liquid handling is implemented, then human intervention decreases, but system cost and complexity increase
Solution Approach 1:
The filter tip is designed to be compatible with standard robotic liquid handlers without requiring specialized accessories. It performs filtration, solid phase extraction, and analyte delivery using only the basic pipetting functions of conventional robots. This universality enables automated sample preparation while avoiding the need for complex, expensive specialized robotic systems.
Solution Approach 2:
The filter tip is designed to be self-contained and self-sufficient, requiring no external vacuum sources, magnetic fields, or pressure systems. It performs filtration and extraction using only the pressure differential created by standard robotic pipetting actions. This self-service design enables automation with simple, inexpensive robotic liquid handlers.
4Reliability
If centrifugation is used for separation, then protein removal is effective, but processing time and equipment requirements increase
Solution Approach 1:
The patent extracts the separation function from the precipitation step and places it in a dedicated filtration step using filter tips. Instead of relying on centrifugation to separate proteins during precipitation, the method allows precipitation to occur statically, then transfers the supernatant to filter tips for rapid filtration. This extraction of the separation function into a dedicated step reduces processing time while maintaining protein removal efficiency.
Solution Approach 2:
The patent replaces the mechanical centrifugation system with a pressure-driven filtration system using filter tips. The filtration is driven by the pressure differential created during standard robotic pipetting, eliminating the need for centrifugation equipment and reducing processing time while maintaining effective protein removal through the filtration membrane.
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 enables quicker, more efficient sample preparation with reduced errors and costs, improving laboratory throughput by eliminating the need for complex robotic systems and minimizing sample contamination and ion suppression, while maintaining high recovery rates of analytes.
Implementation Method 1
a filter pipette tip fitted with at least a filter, and optionally, a substrate, a sorbent, a barrier, or a combination thereof
Implementation Method 2
a filter pipette tip fitted with at least a filter, and optionally, a substrate, a sorbent, a barrier, or a combination thereof
Data Source
AI summary
Devices and methods for performing pre-analysis sample processing of biological and chemical samples using robotic liquid handlers are disclosed. Methods for solid phase extraction, protein precipitation and filtration of biological and chemical samples using automation and the devices in a rapid and convenient way are described.