Get the Whole Picture with BMI: What You’re Not Seeing Can Hurt You
Particle characterization and analysis technology has long been limited; only providing a tiny glimpse into what's actually present in formulations—leaving important questions unanswered.
Halo Labs uses Backgrounded Membrane Imaging (BMI), a high-contrast imaging technique, to help solve these problems. BMI brings clarity to formulation risks that were previously hard to see, breaking through traditional limits quickly and accurately. One minute is all it takes to analyze a sample. With the ability to test 96 samples in less than two hours, it's a valuable tool for drug development.
Backgrounded Images: The Key to Sensitive Robust Early Stage Particle Characterization
BMI uses sophisticated image processing techniques to analyze images and acquire particle data. The key is to first take a background image of the membrane.
Following sample filtering for particle capture, the same membrane is re-imaged, this time with particles on the surface. The "background image" is precisely aligned with the "measure image," and then subtracted pixel by pixel to remove the background texture and reveal the particles.
Due to measuring particles against air instead of liquid, the refractive index contrast in BMI is 10x greater than in liquid measurements such as light obscuration and flow imaging, providing the increased sensitivity required for robust early stage particulate detection. Aura uses high powered optics and sensitive sensors to image particles, and the analysis is fully automated.
See how BMI in combination with Fluorescence Membrane Microscopy (FMM) provides unprecedented insight into particle analysis.
Biological aggregates are mechanically compliant and lay flat on the surface of the membrane (left), whereas extrinsic contaminants protrude, providing greater SIMI signature (right).
How BMI Works
Particle characterization and analysis has never been simpler. With this innovative technology, you can screen up to 96 samples quickly and easily in just three steps:
- Backgrounded Membrane Imaging begins with imaging a new membrane plate.
- Pipetted samples are then placed into separate wells on the membrane, and a gentle vacuum is applied.
- Finally, load the plate once more and hit the "measure" button—it’s that straightforward.
Why Choose BMI
| BMI | LIGHT OBSCURATION | FLOW IMAGING | |
|---|---|---|---|
| LOW VOLUME REQUIREMENTS |
Requires 5 µL – 100X less than competition.
|
Requires 5 mL.
|
Requires 500 µL.
|
| HIGHLY REPRODUCIBLE |
CVs of polydisperse samples under 6%.
|
Highly variable on polydisperse samples.
|
Highly variable on polydisperse samples.
|
| CONSUMABLE |
ZERO particle carry over, cross contamination & washing.
|
Multiple components that require washing.
|
Expensive flow cell that requires washing.
|
| HIGH REFRACTIVE INDEX CONTRAST (HIGH SENSITIVITY) |
Dry based measurement = analyze small & dim particles with higher fidelity.
|
Low contrast, liquid based measurement.
|
Low contrast, liquid based measurement.
|
| FLUIDICS FREE |
ZERO purge volume, leaking & clogging.
|
Fluidics-based.
|
Fluidics-based.
|
| NO CONFOUNDING “PARTICLES” |
Air bubbles not measured.
|
Air bubbles counted as particles.
|
Air bubbles counted as particles.
|
| INSTRUMENT COMPATIBILITY |
Particles on membrane can be analyzed later with other instruments.
|
Sample ends up in waste, no additional analysis possible.
|
Sample ends up in waste, no additional analysis possible.
|
Featured Applications
Biologics – Late Stage Formulation
Cell Therapy – Product Purity
Cell vs. Non-Cell Characterization
Featured Products
Aura+
With the ability to support the full range of development and manufacturing applications across therapeutic approaches—including protein/antibody therapeutics, gene therapies, cell therapies, and small molecules— Aura+ packs powerful flexibility into a single particle analyzer.
Features
- 5 µL to 10 mL volume
- Particle characterization for protein, cell and gene therapeutics
- Three fluorescent channels for particle identification
- 4x and 20x magnification imaging
Aura PTx
Get the most out of your protein therapy quality measurements with Aura PTx. Our advanced technology can quickly detect, count and characterize excipients and subvisible particles, giving you valuable insights into drug stability during early stages of product development.
Features
- Fluorescence enabled for protein analysis and immunoassays
- Degraded polysorbate and excipient analysis
- High throughput, low volume platform for formulations development
- USP 788 compliant
Frequently Asked Questions
Backgrounded membrane imaging, which is used by the Aura PTx and Aura+ instruments, is a valuable alternative for particle detection of biotherapeutics because it offers several advantages over traditional methods such as microscopy or flow imaging. Backgrounded membrane imaging uses a specialized membrane with a dark background, allowing for enhanced contrast and improved visualization of particles. This technique enables rapid and accurate analysis of subvisible particles in biotherapeutic formulations, helping ensure product quality and safety.
USP 787 and USP 788 are both chapters in the United States Pharmacopeia (USP) that address particulate matter in injections. However, they focus on different aspects of particulate matter testing. USP 787 provides general guidelines for particulate matter testing, including sample preparation, particle counting methods, and acceptance criteria. In contrast, USP 788 specifically outlines the requirements for particle size limits and methods of particulate matter determination in injections for various dosage forms.
A particle sizer works by measuring the size distribution of particles in a sample. Different particle sizing techniques, such as laser diffraction, dynamic light scattering (DLS), or microscopy-based imaging, are used depending on the instrument's design and application. For example, in laser diffraction, a laser beam is directed through the sample, and the scattered light is detected at various angles to determine particle sizes. In dynamic light scattering, fluctuations in scattered light caused by Brownian motion of particles are analyzed to determine particle sizes. The Aura particle analyzers use a combination of background microscopy and fluorescence to determine the size and aggregation of particles. Particle sizers provide valuable information about the size distribution of particles, aiding in product development, quality control, and research applications.
