Spectradyne

Spectradyne is a company in southern California that makes instruments for counting and sizing particles from about 30 nanometers to a few micrometers across in a drop of liquid. Each particle is pushed through a constriction in a disposable cartridge, and the instrument records the dip in electric current as it passes. The company calls the method microfluidic resistive pulse sensing (MRPS).^[1] It is the Coulter principle of the Coulter counter, applied to a constriction a few hundred nanometers to a few micrometers wide.

Its first instrument, the nCS1, measured size distributions and absolute concentrations from 3 microliters of sample. A later instrument, the ARC, adds fluorescence to the electrical measurement so that particles of one kind can be picked out of a mixture.^[2] The National Center for Advancing Translational Sciences, part of the National Institutes of Health, awarded the company a $1.6 million Phase II Small Business Innovation Research grant for the ARC.^[2]

The method came out of a physics laboratory at the University of California, Santa Barbara. In 2011 five authors from the department described "a high-throughput label-free nanoparticle analyser" in Nature Nanotechnology: a microfluidic instrument that detects nanoparticles one at a time. They measured synthetic particles and unlabeled bacteriophage T7 in salt solution and in mouse blood plasma, and in the plasma they found a large background of naturally occurring nanoparticles whose sizes followed a power law.^[3]

The company was founded in 2013. The university's startup timeline credits Fraikin, an alumnus, and Meinhold, a researcher there.^[4] The National Institutes of Health names four founders: Jean-Luc Fraikin, who is chief executive officer, Andrew Cleland, who led the university laboratory where the technology began, Franklin Monzon and Peter Meinhold.^[2] In June 2016 all four published an application note on the nCS1 in American Laboratory, giving the company's address as Torrance, California.^[1]

The sample, 3 microliters in a salt solution of a few tens to a few hundred millimolar, is pipetted into a reservoir on a cartridge. A small voltage across the constriction drives an ionic current, and the constriction, which the note gives as "a few hundred nanometers to a few microns in diameter", is the only path between the two sides. Any particle inside it blocks part of the current for as long as it stays. The depth of the dip is proportional to the volume of the particle, so a gold bead and a polystyrene bead of the same diameter give the same signal, and the width of the dip gives the speed.^[1]

Speed matters because it gives the flow. The instrument calculates the flow rate from the pulse durations and the geometry of the constriction, and with the flow it converts a count of pulses into a concentration. The cartridge is cast from a reusable mold, and cartridges from one mold agree to within a few percent on reference particles traceable to the National Institute of Standards and Technology. Results are reported as a concentration spectral density, in particles per milliliter per nanometer.^[1] The note lists a size range from 30 nm to a few micrometers, concentrations from 10⁷ to 10¹² particles per milliliter, and count rates of about 10⁴ particles a second.^[1]

Each cartridge has one fixed constriction and covers a limited range of sizes. Izon Science makes the same kind of measurement with a pore in an elastic membrane that is stretched to change its size, a method described in tunable resistive pulse sensing.

Because the signal depends on volume alone, the nCS1 counts every particle in a sample whatever it is made of, and it cannot say which kind it has counted. The ARC's fluorescence is meant for samples that hold more than one kind of particle, since it lets a user pick out the target particles from a mixture.^[2] Applications named by the National Institutes of Health include checking the dose of nanoparticles in an experiment, characterizing nanoparticle drugs and biomarkers, and measuring the lipid nanoparticles of messenger RNA vaccines.^[2]

Molecular Reality Corporation streams the current through a hole about 200 micrometers wide, a size closer to a Coulter counter than to a nanopore.^[5] The constrictions in Spectradyne's cartridges, a few hundred nanometers to a few micrometers wide, lie between that hole and a nanopore.^[1]

• Resistive pulse sensing
• Tunable resistive pulse sensing
• Coulter principle
• Izon Science