Polystyrene bead

A polystyrene bead is a sphere of polystyrene, a clear plastic, a few tens of nanometers to some tens of micrometers across and uniform in size to within a few percent. Because the sphere is rigid, insulating, round and can be bought in a chosen size, it is the usual test particle for resistive pulse sensing: a bead of known diameter gives a pulse of known height, and the pulse sizes the pore. The same beads, with chemical groups on their surfaces, stand in for viruses, vesicles and cells when the real thing is inconvenient, which is why they are named as the analytes of the planned virology game SARS Invaders.

Polystyrene is a polymer of styrene with a density of about 1.05 g/cm³, slightly above that of water, so large beads settle slowly and small ones stay suspended. Beads are made by emulsion polymerization, in which styrene dispersed in water polymerizes inside tiny particles that grow into spheres. The surfaces carry whatever the chemistry leaves there: sulfate groups from the initiator, carboxyl groups if acrylic acid is added, amines if the surface is aminated. All of these change the charge of the bead, and a typical sulfate bead carries a negative charge that keeps it from clumping in water of low salt.

In a Coulter counter or nanopore a bead raises the resistance of the pore by about the volume of electrolyte it displaces. For a bead much smaller than the pore, the fractional increase is to first order d³/(D²L), where d is the bead diameter and D and L are the diameter and length of the pore; it is 3/2 of the fraction of the pore volume that the bead fills, a factor that goes back to Maxwell's treatment of spheres in a conductor. A bead 100 nm across in a pore 500 nm wide and 1 µm long would reduce the current by about 0.4 percent.

The first sub-micrometer demonstration used the beads. In 1970 DeBlois and Bean passed polystyrene spheres 90 nm across through a single pore etched in plastic and counted and sized them one at a time.^[1] Beads are still the usual first test of a new sensor: a pore in a chip, a carbon nanotube or a glass nanopipette is judged by whether it sees them and reports their size correctly. Ito, Sun and Crooks used a single carbon nanotube to determine both the size and the surface charge of individual polystyrene nanoparticles.^[2] In a nanopipette, one bead has been sent back through the orifice thousands of times, to narrow the uncertainty of its mean size (see Ping-pong sensing).^[3]

Coating the beads makes them report on chemistry. Saleh and Sohn coated latex colloids with streptavidin, passed them through an artificial pore in a chip, and measured the growth in diameter as antibodies bound to them.^[4]

Beads are also reference materials. The National Institute of Standards and Technology developed a set of five, from 0.3 to 30 µm. The 10 µm one has an unusual origin: its spheres were grown in microgravity aboard the Space Shuttle Challenger on the STS-6 mission in April 1983, where gravity does not settle the growing spheres, and it became standard reference material 1960. Its certified mean diameter is 9.89 ± 0.04 µm, with a standard deviation of 0.09 µm, less than one percent of the diameter. NIST describes it as the first commercial product made in space.^[5]

Molecular Reality Corporation named beads in its plans for the games that were to run on Maxine's Quest. In the memo "Early Releases on Maxine's Quest", the entry for the virology game gives its major analytes as "polystyrene beads with different surface functionalities, lipid particles", and adds: "Focus on selective algorithm development, no real viruses involved in the early phase."^[6] The coronavirus that causes COVID-19 is 60 to 140 nm across,^[7] so a bead of that size gives a pulse comparable to that of a virion and can be made to carry the surface groups that would, in a real sample, set one virus apart from another. The game was not released.

• Coulter principle
• Surface charge (nanopore)
• Current blockade