This story has been updated to correct the names and capabilities of forthcoming Fluidic Analytics instruments.
NEW YORK (GenomeWeb) – Protein research firm Fluidic Analytics has launched the first in what company officials said will be a series of instruments for studying native proteins and protein complexes.
The device, called the Fluidity One, monitors the diffusion of proteins as they flow through a microfluidic channel to assess their size and concentration, allowing researchers to identify, for instance, protein aggregation linked to disease processes or protein interactions.
The instrument is designed for the analysis of purified protein samples, said Sean Devenish, Fluidic Analytics' head of research and development, but the company plans to launch new versions of the device every 12 to 18 months, he added, with the next release allowing for the analysis of labeled proteins mixed into complex matrices like blood or cell lysates, and the release after that allowing for proteome-scale analysis of protein interactions in biological samples.
Fluidic Analytics was founded in 2015 to commercialize technology developed in the lab of Tuomas Knowles, professor of chemistry at Cambridge University and the firm's chief scientific officer.
The company's technology is based on the fact that at the microfluidic scale, fluids flow in a laminar manner, meaning two streams will run next to each other smoothly without the sort of mixing seen at a normal scale. Taking advantage of this fact, the firm's devices run two streams of fluid side-by-side down a microfluidic channel — one stream containing the protein sample of interest, and the other stream consisting of an auxiliary fluid. Under the microflow conditions, the only way the protein can move from one stream to another is by diffusion, and this diffusion rate is inversely proportional to the size of the proteins, with small proteins diffusing more quickly.
By measuring the amount of protein that diffuses from the sample to the auxiliary stream throughout the course of a run, researchers are able to assess the size of the proteins in the sample. To make this measurement, they collect the output of the two streams, label the proteins with a dye targeting primary amines, and measure them using fluorescence microscopy, with the relative intensity of fluorescence between the two streams indicating how much protein diffused.
In the case of a purified protein sample, as the Fluidity One is meant to analyze, this measurement could allow users to assess, for instance, what proportion of the proteins in a sample are single proteins as opposed to aggregates or proteins bound to another interacting molecule.
According to Devenish, the system offers several advantages over existing methods for analyzing protein size, most notably the fact that it is done entirely in solution and under native conditions without labeling, which means proteins are not denatured or otherwise altered by the analysis. The platform can also work with small samples (5 μl) and returns results in eight minutes.
Knowles' lab developed the technology to study protein aggregates involved in conditions like prion diseases and Alzheimer's, Devenish said, and the company is marketing this initial device for applications including protein quality analysis and the study of protein interactions and protein aggregation.
He said that the next version of the device, which the company has named the Fluidity One-W and has begun prototyping and aims to launch in the next 12 to 18 months, will allow researchers to introduce labeled proteins of interest into biological samples in order to, for instance, identify interactions between those target proteins and molecules endogenous to the biological sample.
He suggested it could be useful for applications including transplant donor-patient matching, where researchers could take labeled human leukocyte antigens from the donor and screen them against the recipient's blood to look for antibody binding.
Ultimately, Devenish said, the goal is to develop an instrument capable of analyzing complex samples on a proteome-scale enabling, for instance, large-scale studies of protein-protein interactions.
That device, tentatively named the Fluidity Two, would use two forms of solution phase separation to initially separate the different proteins in a sample with those separated proteins then being passed through the flow channel or multiple flow channels for analysis, Devenish said.
"Where we want to end up is being able to look at the protein interactions in a sample on a holistic scale," he said. "We think that is really where a lot of biological information is going to reside."
In this the company's thinking is trending with much of the proteomics world where interest has grown and tools have emerged for studying proteins not as discrete entities but within their actual biological context, as parts of complexes with other proteins and molecules.
One challenge to analyzing complex samples will including methods for in-solution separations to allow for proteome-scale analysis. Devenish said the company and its collaborators at Cambridge were looking at a variety of options, with isoelectric focusing being a leading contender.
He also noted that the company was considering coupling the instrument to a technology like mass spectrometry to identify the specific protein interactions detected by the system.
The Fluidity One is currently available for purchase and sells for £21,000 ($27,450) in Europe, Devenish said. The list price is $30,000 in the US.
Fluidic Analytics has around 30 employees and has raised £7 million to date and plans to close a Series C funding round later this year. The company believes that additional funding will be sufficient to develop and bring the Fluidity One-W and Two instruments to market, Devenish said.