Flow Cytometer Autofluorescence Reduction via Microfluidic Cartridge Alignment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Flow cytometers are complex and expensive, requiring precise setup and calibration for effective particle detection and analysis, which limits their accessibility and efficiency in processing particle-bearing fluid samples.
Innovation Solution
A microfluidic interrogation apparatus with an indexing structure, a source of stimulation radiation, adjustment means, and sensor means is developed to detect and analyze particles, optimizing the signal-to-noise ratio and enabling rapid processing of multiple samples in a compact, user-friendly format.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional flow cytometers are used for particle detection, then detection capability is achieved, but device complexity and cost increase
Solution Approach 1:
The system divides the flow cytometry function into separate components: a disposable microfluidic cartridge containing the interrogation aperture and fluidics, and a separate interrogation device. This segmentation allows the complex detection function to be isolated in a standardized cartridge while the main device remains simpler and reusable.
Solution Approach 2:
The invention employs disposable microfluidic cartridges that are discarded after use, eliminating the need for complex cleaning, calibration, and maintenance of the main interrogation device. The cartridge contains all consumable components (fluidics, aperture, reagents) that would otherwise require maintenance in a conventional flow cytometer.
2Measurement precision
If conventional flow cytometers are used for particle detection, then detection capability is achieved, but cost increases
Solution Approach 1:
By separating the disposable cartridge from the reusable interrogation device, the system allows mass production of standardized cartridges using cost-effective microfluidic fabrication techniques, while the expensive interrogation device is shared across multiple cartridges and samples.
Solution Approach 2:
The disposable cartridge approach eliminates expensive maintenance, calibration, and cleaning operations. Each cartridge is manufactured at low cost using standardized processes and discarded after a single use, reducing the total cost of ownership compared to conventional flow cytometers that require expensive service and maintenance.
3Measurement precision
If precise alignment of radiation beams is performed, then signal-to-noise ratio is improved, but setup time and complexity increase
Solution Approach 1:
The microfluidic cartridge is pre-fabricated with the interrogation aperture precisely positioned and aligned relative to the radiation source and detector pathways. This preliminary alignment during manufacturing eliminates the need for complex alignment procedures during setup and operation.
Solution Approach 2:
The cartridge design incorporates self-aligning features such as mechanical stops, keyed interfaces, and tolerance-built pathways that automatically position the interrogation aperture correctly when the cartridge is installed in the interrogation device, eliminating manual alignment requirements.
4Measurement precision
If autofluorescence is reduced, then detection sensitivity is improved, but device complexity increases
Solution Approach 1:
The system extracts and isolates the sample interrogation from all sources of autofluorescence by using a disposable cartridge that can be pre-treated or coated to minimize background fluorescence. The cartridge design allows selection of materials with low autofluorescence properties while keeping the main device simple.
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 apparatus enhances the detection and analysis of particles by optimizing the signal-to-noise ratio, reducing autofluorescence, and improving the alignment of radiation beams, resulting in a more efficient and cost-effective flow cytometry process.
Implementation Method 1
The wavelength of a radiation source (typically a laser), is matched to the excitation wavelength of the fluorescent tag. The tagged particles fluoresce in the cytometer, in accordance with a phenomena widely known as Stokes-shift, when excited by a laser beam.
Implementation Method 2
The interrogation typically includes directing a light beam from a radiation source, such as a laser, transversely across the focused stream of single-file particles. The light beam is scattered by each particle to produce a scatter profile.
Data Source
AI summary
A flow cytometer including a laser, indexing structure, adjustment structure, and sensor structure. The cytometer is conventionally used with a removable microfluidic cassette, which is installed at a first position that is enforced by the indexing structure. The adjustment structure changes a relative position between an interrogation aperture of the cassette and the laser beam. Feedback from the sensor structure is used to optimize propagation of the laser through the interrogation aperture to reduce (and hopefully eliminate) autofluorescence caused by beam impingement onto the cassette.