Single-Cell Dispensing Detection at Fluid Entry in Microtiter Wells
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Solution Overview
Problem
Existing methods for detecting cells or particles in fluid containers, such as microtiter plates, lack reliability, leading to inefficiencies and high economic risks due to the inability to verify the accurate deposition of single cells or particles, which is crucial for monoclonal cell line production.
Innovation Solution
An apparatus and method that coordinates the dispensing of cells or particles with real-time detection in a defined sub-volume of a fluid container, using a detection apparatus to capture images of the sub-volume and its surroundings, ensuring reliable verification of the object's presence before it reaches the bottom of the container.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If cells are deposited into microtiter plates by free-jet printing or pipetting, then single cells can be transferred into wells, but the detection of whether a single cell is actually located in the well becomes difficult and unreliable
Solution Approach 1:
The detection apparatus performs detection in the defined sub-volume of the fluid container before the cell settling process is complete. By detecting cells in the fluid phase at an intermediate stage rather than waiting for final settlement, the system captures cell presence information before refraction and shading effects from well bottom interactions occur, thereby maintaining high detection reliability while supporting precise single cell deposition
Solution Approach 2:
The invention introduces a detection apparatus that operates through the fluid medium itself, using the fluid as an intermediary to access and detect cells in the defined sub-volume. This intermediary detection approach allows observation of cells in their natural fluid environment without requiring direct contact with or settlement on the well bottom, avoiding the optical interference problems that plague bottom-view microscopy
2Reliability
If the entire well bottom is examined under the microscope to verify single cell presence, then detection coverage is complete, but the process becomes extremely time-consuming and prone to errors
Solution Approach 1:
The invention segments the detection task by focusing only on the defined sub-volume of the fluid container where cells are deposited, rather than examining the entire well bottom. This spatial segmentation reduces the detection area from the full well bottom surface to a specific sub-volume, dramatically reducing examination time while maintaining reliability for the critical deposition region
Solution Approach 2:
The detection apparatus performs detection at an intermediate stage before cells have fully settled to the well bottom. By conducting preliminary detection in the fluid phase, the system obtains verification information about single cell presence without requiring complete settlement and extensive bottom examination, thereby reducing time loss while maintaining detection reliability
3Measurement precision
If high-resolution imaging is performed to detect cells at the well bottom, then detection precision is improved, but refraction and shading effects cause misidentification and increased economic risks
Solution Approach 1:
The detection apparatus performs detection in the defined sub-volume of the fluid container before cells settle to the well bottom and before optical interference effects can develop. By conducting detection at this preliminary stage in the fluid phase, the system achieves high measurement precision without being affected by refraction and shading artifacts that occur during bottom-view microscopy
Solution Approach 2:
The invention uses the fluid medium as an intermediary to detect cells in their suspended state, avoiding direct optical interaction with the well bottom that causes refraction and shading effects. This intermediary detection approach maintains high measurement precision by observing cells through the fluid rather than through the well bottom interface
4Manufacturing precision
If centrifugation is performed to transport cells to the bottom before detection, then cell positioning is improved, but the process complexity and time required are increased
Solution Approach 1:
The detection apparatus performs detection in the defined sub-volume before centrifugation or other cell settling operations are completed. By detecting cells in the fluid phase at this preliminary stage, the system obtains verification information without requiring the additional complexity of centrifugation equipment and procedures, thereby reducing device complexity while maintaining sufficient positioning information for verification
Solution Approach 2:
The invention allows the detection system to verify cell presence and positioning using the natural position of cells in the fluid during or before the settling process, without requiring active intervention to move cells to a specific location for detection. This self-service approach reduces process complexity by utilizing the existing cell distribution rather than requiring active repositioning
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 reliable and efficient detection of cells or particles directly upon entry into the fluid container, reducing process time and complexity, eliminating shading and refraction issues, and ensuring accurate identification without the need for additional steps like centrifugation or horizontal scanning.
Implementation Method 1
a detection apparatus configured to, in a time-coordinated manner with dispensing the at least one cell or the at least one particle by the dispenser, perform a detection in the defined sub-volume
Data Source
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AI summary
A apparatus for detecting cells or particles in a fluid container comprises a dispenser configured to dispense at least one cell or at least one particle into a defined sub-volume of a fluid with which the fluid container is at least partially filled, and a detection apparatus configured to, in a time-coordinated manner with dispensing the at least one cell or the at least one particle by the dispenser, perform a detection in the defined sub-volume and/or in one or several sub-volumes underneath the defined sub-volume in order to sense the at least one cell or the at least one particle when entering the fluid or immediately after entering the fluid.