Chemometrics* is an umbrella term for a set of mathematical techniques applied to information that is of chemical interest. Similar techniques are applied to other fields of study, and the names reflect the interest (e.g., econometrics, sociometrics, psychometrics, etc.).
There’s a fairly wide range of application of the mathematical methods, although some of them have restricted utility. For example, Paul Gemperline, a professor at East Carolina University, uses mathematics to extract reaction rate constants from data measured from complicated mixtures of multiple successive reactions. However, the vast majority of interest and applications comes in the area of analytical chemistry, where the mathematical techniques *Editor’s Note - This is the first in a series of articles, Demystifying Chemometrics, that will address this subject.
are applied to data from analytical instruments, notably spectrometers.
Spectroscopy is a premier method of performing both qualitative and quantitative analysis, but runs into difficulties when the sample is a complex mixture of ingredients. Ingredients typically have different spectra and when sampled individually, each is simple to recognize. When an unknown number of them are mixed together in unknown amounts, it can be difficult to determine what and how much of each ingredient is present.
Historically, this problem was solved by chemists doing laboratory separations. Using the chemical properties of the known or suspected materials to selectively cause reactions, chemists could weed out the other materials until only the desired analyte was left. Various forms of measurement of the quantity were used, but even here, sometimes the final measurement was made using spectroscopic methods.
More recently, various types of chromatography were used. The physical properties of the different ingredients were used to separate the analyte from the interfering materials, allowing identification and measurement. Again, various types of measurement detectors were used: thermal conductivity, flame detection, etc. Often, a spectrometer was incorporated into the chromatograph to measure the quantity of the analyte as it emerged from the chromatographic process.
Both wet chemical and chromatographic methods have limitations. They are tedious and time-consuming, require an expert chemist and necessitate a continual supply of solvents and possibly other chemicals for the analysis. Along with the supply of chemicals comes a concomitant requirement for the disposal of those chemicals – and the time is long past since it was legally and socially permissible to just dump them down the drain!
Modern Spectroscopic Analysis
Modern spectroscopic methods have been developed to eliminate the need to physically separate the analyte from the other constituents in samples. By doing so, they eliminate the need for obtaining and disposing of the chemicals, provide for a much speedier analytical method that has a lower cost per analysis and can be performed by less-highly trained personnel. In addition, the analysis is non-destructive to the sample, and the amounts or concentrations of multiple ingredients can be measured using a single spectrum from a single sample. Since a computer is available to perform the required manipulations of the data, it can also be used as part of a process-control system. Results can immediately and directly be sent to the process-control computer, or programmed to perform these functions itself.
In order to achieve these benefits, a good amount of “upfront” effort is needed. The chemometric algorithms must relate the properties of interest in the sample to the measured spectra.
Instead of separating the analyte from the matrix using a chemical or physical method and then measuring spectra of the relatively “clean” material, the spectrum of “dirty” material – that is, the analyte in its natural form and in its natural “environment” (the sample) – is measured, and then the spectral information needed to analyze the sample is extracted mathematically. These mathematical methods are “chemometrics.”
The chemometric methods are based on the use of various computer algorithms. They are used either to do quantitative or qualitative analysis. Using chemometric methods with spectroscopic measurements results in a fast analytical method that is simple enough for technicians to perform. Basically, the user “calibrates” or “trains” the instrument to perform the analysis. This training step should be done by an expert to ensure accuracy.
“Training the chemometrics” requires that the user obtain samples representative of all the future variations of those types of samples that the instrument will analyze during routine operation. Choosing the number and the appropriate samples is one of the key steps in creating a good calibration model, i.e., the mathematical model describing the samples that the computer will use in the future to do the actual analyses. Training the spectrometer requires measuring the spectra from all the samples and then saving them to a computer file.
If quantitative analysis is the goal (i.e., quantifying the amount of analyte in that type of material), then the actual values (sometimes called “true values” or “reference values”) of the analyte in each of those samples also must be measured. Typically, this measurement is made using the wet chemistry, or chromatography methods that were already being used for the analysis.
Ensuring the accuracy of the values obtained by applying the reference method to the samples is also critical to the accuracy of the chemometric method. The computer only knows what it’s been “told,” so if erroneous reference values are used, then the chemometric method will produce those erroneous values for its answer.