How Many Cells Can a Microbubble Lift?

Updated on Jun 13, 2021 Share

We hear this question all the time: How many cells can a microbubble lift?

For many users, the most important questions around microbubble-based separation have to do with how many microbubbles to add to a sample. Answering this question requires getting into the total lifting capacity of a microbubble.

Part of the answer derives from how a microbubble engages cells, clumps of cells, or even larger structures such as spheroids or mammospheres. Any of these will rise as long as the combined density of the bubble and its passenger cells remains less than the density of the surrounding fluid.

That’s the good news. The unavoidable flip side is that as more and more cells load onto a bubble, the slower and slower it will rise, so separation times can grow longer.

What Is the Lifting Capacity of a Microbubble?

When isolating fully dispersed cells (such as in a Ficoll or leukopheresis PBMC prep), we have seen microbubbles carrying as many as four cells. Cells may also serve as a bridge between two microbubbles, significantly increasing the lifting capacity of the overall structure.

Estimating the number of cells that can be lifted by a microbubble requires considering two features, one simple and one more complicated.

Absolute Cell Limit

The absolute limit on how many cells can be lifted is set by how many cells can be simultaneously attached to the surface of a sphere. This is a variant of what is known as the kissing sphere problem, which has an extensive history in theoretical geometry. Fortunately, in real life, it is highly unlikely that a microbubble would spontaneously load with the absolute number of cells geometrically possible, so only the easy problem remains.

Fluid Density

The simpler question is how many cells are required to drive the effective buoyancy of the microbubble and its cargo to a value greater than the density of the surrounding fluid. This break even point at which F­_B in Stokes’ Law changes sign (i.e., goes from a floating force to a settling one) is a function of the density of the cells loading onto the bubble.

To find this threshold, you can begin by knowing the individual densities and radii of the microbubble and all of its cargo cells and calculating a total density (which we’ll call ρ_T) and an effective radius of the extended cell-bubble assembly.

Note here that the total density will determine will determine whether the bubble complex sinks or floats, and the effective radius will largely determine the rate at which it does so. The total density is just a volume-weighted average of the densities of the microbubble and its captured cells. There are many options for estimating an effective radius—we suggest that you look at the microbubble-cell complexes under fluorescence microscopy to gauge their overall architecture. Once you have, you can arrive at terminal velocity.