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System Components & Performance Summary

Microscope & Camera

Microscope & Camera Functions

  • 90x magnification
  • Up to 30 fps refresh rate
  • 5.0 megapixels resolution
  • Long working distance (>25 mm)
  • White LED forward lighting

Microscope & Camera Performance

  • Clear images of pinholes acquired on FACSCanto and FACSAria with forward lighting applied
  • Clear images of laser traces acquired on FACSCanto and FACSAria without forward lighting applied

Design Requirements

  • Eliminate potential laser safety risks by implementing a camera with the microscope
  • Reduce size and weight of the overall system for optimized portability
  • Create a mounting method that would allow adaptation with a variety of Flow Cytometers
  • Develop a pinhole illumination system to increase pinhole visibility
  • Implement software to improve speed and accuracy of the laser alignment process

Overview

BD Biosciences designs and manufactures flow cytometers that are largely used in medical and research institutions around the world. Flow cytometers consist of high power lasers that collide with a stream of cells to extract detailed information. The emissions from the cells’ collision with the laser are sent through the pinholes to be analyzed by a computer. This information can be used to determine cell count and biomarker detection for disease and medical research. The alignment and position of these lasers with the cell stream is critical for accurate results.

Over time and through extensive use, lasers become misaligned which may invalidate research data. To achieve successful alignment, field engineers manually tune the laser orientation until it passes horizontally through the center of the pinhole.

To easily observe the laser positions, field engineers from BD Biosciences have been utilizing a simple compound microscope to enhance the field of view. This previous method presented the major safety risk of a magnified stray laser beam entering the microscope and damaging the user’s eye. The goal of this project was to redesign this microscope and provide a new solution to eliminate any potential risk.

Flow Cytometer Laser Alignment System

Carlos Acuña, Justin Chen, Kevin Chen, Daniel Hwang

Department of Mechanical and Aerospace Engineering at University of California, San Diego

Acknowledgements:

Paul Chen - Systems Product Development Engineer at BD Biosciences | Chantell Kuhlmann - Sr. Manager of Systems Engineering at BD Biosciences | Jerry Tustaniwskyj - Professor at UC San Diego | Patrick McGuire - Teaching Assistant | Dennis Sasaki - R&D Associate Director at BD Biosciences, San Diego | Ian Richardson - Machine Shop Technician | Tom Chalfant - Machine Shop Technician

Figure 10: Software determining the positions of the laser and its alignment

Figure 9: Image without PIS (left). Image with PIS activated (right)

Figure 1: Introduction to flow cytometry and laser alignment

Figure 2: Flow Cytometer Laser Alignment System Prototype

Figure 3: Current Solution (left) and Proposed Solution (right)

Figure 4: AD7013MTL Dino-lite Premier

Figure 5: Lit & Unlit Image samples of FACSCanto (top) and FACSAria (bottom)

Mounting Bracket

Bracket Functions

  • Adaptable to a variety of BD Biosciences Flow Cytometers (FACSAria, FACSCanto, FACSVerse, LSRFortessa)
  • Easily mountable and portable
  • Constructed of black anodized aluminum

Bracket Performance

  • Y-Z mechanical stage successfully allowed compatibility with FACSAria, FACSCanto and LSRFortessa
  • FACSVerse compatibility achieved through flipped mounting of the system
  • Bracket system is composed of detachable parts for quick and facilitated mounting

Figure 6: System Mounting Bracket

Figure 7: System mounted to FACSCanto (left), FACSAria (middle), and FACSVerse(right)

Software

Software Functions

  • Assist technician in laser positioning alignment accuracy and speed
  • MATLAB interface
  • User-friendly interface

Software Performance

  • Detected position of the pinhole target and marks the ideal laser position
  • Determined the position of the laser and its angle of misalignment

Future Improvements

  • Create a quick-release mechanism for facilitated mounting
  • Optimize on camera/microscope selection
    • Continue research and testing of cheaper and/or more effective models
  • Develop a method of dampened forward lighting to further improve image quality for a clearer image of lasers and their positions
  • Develop software GUI and software functionality
    • Convert proof of concept software to a final usable tool
    • Detect lasers using edge detection rather blob analysis

Impact on Society

  • Improves and promotes safe work conditions by eliminating stray laser risks for BD Biosciences’ service engineers
  • Presents novel technologies to reassess and renovate traditional manual processes
  • Works towards preventing medical misdiagnosis and reducing erroneous lab results through the improvement of cytometer accuracy

Conclusion

The Flow Cytometer Laser Alignment System is a safe, portable, precise, and inexpensive device that can be easily used to facilitate the laser alignment process of a variety of BD Biosciences flow cytometer product families. This progressive technology embodies a combination of forward thinking engineering and user-centered design that marks the first steps to the enhancement of current outmoded alignment processes.

Pinhole Illumination System (PIS)

PIS Functions

  • Illuminate pinhole for improved visual reference of target area
  • Adaptable to pre-existing BD Biosciences Filters
  • Easy to reproduce

PIS Performance

  • Pinhole visibility increased without overbearing lasers

Figure 8: Pinhole Illumination System

References:

[1] "Introduction to Flow Cytometry." Introduction to Flow Cytometry. Abcam, n.d. Web. 06 June 2014.

[2] Optics, Edmund. "Understanding Microscopes and Objectives." Edmund Optics. N.p., n.d. Web. 06 June 2014

[3] Bose, Arindam. “How to Detect and Track Red Objects in Live Video in MATLAB” http://arindambose.com/blog/?p=72

[4] Becton Dickenson. "Flow Cytometry." Instruments, Software, and Resources. N.p., n.d. Web. 06 June 2014.

[5] Chen, Paul S. Flow Cytometer Laser Imaging Alignment System. San Diego: BD Biosciences, n.d. PDF.