Electrospray Ionization Probe for Direct Biological Sample Analysis
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Solution Overview
Problem
Current methods for imaging mass spectrometry, such as MALDI, require pretreatment of biological samples and are not suitable for live cells or samples with high salt concentrations, and often necessitate solvent dilution, limiting their applicability and resolution.
Innovation Solution
An ionization method and apparatus using electrospray that allows direct analysis of living cells or biological samples without pretreatment, capable of operating under atmospheric pressure and producing electrospray even with high salt concentrations, without the need for solvent dilution, utilizing a hollow insulated sample holder with a small tip and an electrically conductive linear body that can be projected outward to ionize samples using a high voltage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If MALDI method is used for imaging mass spectrometry, then molecular analysis can be performed, but pretreatment of biological samples is required
Solution Approach 1:
The invention extracts the ionization function from the complex MALDI pretreatment process by using a separate electrospray ionization source that can directly ionize samples without requiring matrix coating or other preparatory steps. The ionization source is designed to work independently with minimal sample preparation.
Solution Approach 2:
The invention introduces an intermediary electrospray ionization source between the sample and the mass analyzer. This intermediary component handles the ionization process separately, allowing the sample to be introduced in a simpler form while still achieving the required ionization for mass spectrometry analysis.
2Measurement precision
If conventional electrospray is used, then ionization can be achieved, but solvent dilution is necessary for high salt concentration samples
Solution Approach 1:
The invention changes the operational parameters of the electrospray system, specifically operating at atmospheric pressure with optimized voltage and flow conditions that enable direct ionization of high salt concentration samples without requiring dilution. This parameter optimization allows the system to handle samples in their native state.
3Ease of operation
If atmospheric pressure operation is implemented, then direct analysis of living cells is enabled, but ionization efficiency may be reduced
Solution Approach 1:
The invention creates a localized high-voltage field region within the atmospheric pressure environment, concentrating the ionization energy in a specific zone where the sample passes through. This local concentration of ionization capability maintains efficiency despite the atmospheric pressure conditions.
Solution Approach 2:
The invention employs periodic pulsing of the high voltage to the electrospray source, creating repeated ionization events that enhance overall ion production. This periodic action compensates for the reduced ionization efficiency that would occur under continuous atmospheric pressure operation.
4Measurement precision
If high voltage is applied continuously, then ionization is maintained, but sample consumption increases
Solution Approach 1:
The invention uses periodic or pulsed high voltage application rather than continuous voltage, creating ionization bursts that are sufficient for detection while significantly reducing the total sample consumption. The timing of these pulses is optimized to coincide with sample introduction.
Solution Approach 2:
The invention maintains continuous sample flow through the system while applying intermittent high voltage, ensuring that ionization opportunities are continuously available without requiring continuous high voltage application. This approach maintains ionization effectiveness while minimizing sample usage.
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 the direct analysis of living cells and biological samples with high salt concentrations under atmospheric pressure, improving resolution and eliminating the need for solvent dilution, while allowing for improved S/N ratio through repetitive ionization and surface activity-based detection.
Implementation Method 1
introducing a sample into at least a tip portion of a hollow insulated sample holder having a small hole in the tip portion
Implementation Method 2
applying a high voltage to the linear body at least in a portion of a time period in which the tip of the linear body is being projected outwardly from the hole, thereby ionizing, by electrospray, the sample adhering to the tip of the linear body
Data Source
AI summary
It is arranged so that living tissue that has not been pretreated can be adopted as a sample of interest. A sample is introduced into at least a tip portion of a hollow insulated sample holder 11 having a small hole 11a in the tip portion. A slender metal wire 12, which has been inserted into the sample holder 11 from the rear, is projected outwardly from the sample holder 11 through the hole 11a while being brought into contact with the sample. A high voltage is applied to the slender metal wire 12 at least in a portion of a time period in which the tip of the slender metal wire 12 is being projected outwardly from the hole 11a, thereby ionizing, by electrospray, the sample adhering to the tip of the slender metal wire 12. The ions are introduced into an analyzing apparatus and are analyzed.