This blog is a collaboration between the LCGC and the American Chemical Society Analytical Division Subdivision on Chromatography and Separations Chemistry.
The science of separations within microfluidics has already begun to have a significant impact in a number of areas. But often they are embedded in a larger system – their importance is masked or downplayed.
The tiny length scale of microfluidics enables things that have no equivalent on the bench. For example, extremely large electric fields and gradients can be induced, which is impossible on the macroscopic scale. When resolution is coupled with the value of these elements, it can skyrocket. If the details of the techniques naturally lend themselves to multi-step separations or improve detector function, the impact of advanced resolution is multiplied.
I started wondering “by how much?” Can I estimate how much better the separations can be and how well joint mass specification, cryoEM, spectrophotometry or NMR might work? What is the real “impact?” If I want to answer such a question, what are my measurements? What do I put on X– and there-axes when I will plot it? “Impact” didn’t seem to work well as an analytical metric.
I can make a quick estimate of the maximum capacity (the number of distinct pieces of information that can be collected), coupled with the maximum and minimum resolution and elution time or spatial elements. Microfluidics can provide ten to a thousand times greater peak capacity on a single axis. Sounds pretty good, right? So what. What does it actually do mean? How to understand the impact of such a thing?
Cue my ignorance of entire fields of science.
Like most things in my career, someone else has been thinking about this stuff for a long, long time, and I just didn’t know it. And of course they didn’t use any words that I would look up or understand initially. A lucky few wandering through an old literature on gas chromatography and mass spectrometry from the 60s and 70s*, as well as a friendship with a mathematician, was the key.
A new world for me: information theory. They have been there for a long time. The original pilot had to (to my knowledge) estimate how much information could be transmitted over the transatlantic cable. To understand the impact of an analytical technique, I needed to examine ships, cables, oceans and electronics? Obvious, right?
Buried in their analysis was a formula for the smallest “size” (bit) of information relative to the total width of that information, which in our world is the maximum capacity. Also, the amplitude range can be quantized in the same way for “informational content” or bits (these parts are quite easy to understand, of course only in hindsight). The core of this is reflected in Shannon’s equation:‡
Suitable for the science of separations, this can give the number of “bits” of information available from that system.
Cue more ignorance.
It turns out that spectroscopists, faced with similar problems, attacked them with concepts consistent with Shannon’s equation. Kaiser wrote two “A-page” articles in 1970 (Anal. Chem. 42 (2970) 24A) which explains these concepts applied to the identification and quantification of all elements in lunar rock samples. A truly fascinating read. In this article, he defines the “informational power” of an overall technique (in available bits) and the “informational volume” of this technique applied to a particular problem. Importantly, also defined is the amount of information necessary from the sample or the problem posed.
Now I have the tools, a way to estimate and compare the informational power of a separations science technique in terms of available bits of information. I also have a construct for estimating the volume of information needed to attack a particular problem.
On this second point arises an interesting question with which we play: how much information is contained in the blood? It seems ridiculous to ask such an open-ended question. But with these strategies listed by information theory, it can be considered. Think of cells, small bioparticles (eg exosomes), proteins, peptides, small molecules and organic and inorganic ions; define the maximum/minimum concentrations and the smallest clinically relevant or biologically important difference in concentration and ta-da, you have it. That’s a huge number that we’re still refining, but for argument’s sake, let’s set it to 1022 bits. There are equally large numbers for a number of other systems (environmental samples, search for life in the solar system, etc.).
Is it possible to create analytical techniques to match this volume of information? Well, when you start going through the numbers and the math, the simple answer is yes, but the keys are microfluidics and the multiplying factors of having multiple axes and the amplification of information-rich sensing patterns. When we multiply the exponents, they increase very quickly. Coupled with that outrageous (yes, outrageous – I just said you can get 1022 pieces of information from blood – you didn’t notice, did you?). The different axes of separation and detection must be compatible in time, space, configuration and concentration.
We are in the process of writing an academic article in this space. I’m sure we stray a little into the details here and there, but the numbers are so important that it won’t change the conclusion. When the science of separations is fully exploited and combined with information-rich detectors, the amount of information available will challenge data storage and computational systems: the bottleneck will no longer be analysis.
On to my next ignorance and thanks for reading
*Z Anal. Chem. 245, 84 (1969); J. Chromatogr. 172, 15 (1979); J. Chromatogr. A 79, 157 (1973); Anal chemistry 46, 283 (1974).
‡ VS : channel capacity (bits/s) or information rate; B : bandwidth (Hz) or bandwidth; S : power of the signal received (watts or V2); NOT : power of noise (watts or V2) and interference over the bandwidth, measured in watts (or volts squared).
This blog is a collaboration between LCGC and the American Chemical Society’s Analytical Division Subdivision on Chromatography and Chemistry of Separations (ACS AD SCSC). The objectives of the subdivision include
- promotion of chromatography and chemistry of separations
- organize and sponsor symposia on topics of interest to separation chemists
- develop activities to promote the growth of the science of separations
- increase professional status and contacts between separations scientists.
For more information on the development or to get involved, please visit https://acsanalytical.org/subdivisions/separations/.