Having noted that each area of chemistry brings a unique perspective to the study of chemistry, let’s ask a second deceptively simple question: What is the analytical perspective? Many analytical chemists describe this perspective as an analytical approach to solving problems.
For different viewpoints on the analytical approach see (a) Beilby, A. L. J. Chem. Educ. 1970, 47, 237-238; (b) Lucchesi, C. A. Am. Lab. 1980, October, 112-119; (c) Atkinson, G. F. J. Chem. Educ. 1982, 59, 201-202; (d) Pardue, H. L.; Woo, J. J. Chem. Educ. 1984, 61, 409-412; (e) Guarnieri, M. J. Chem. Educ. 1988, 65, 201-203, (f) Strobel, H. A. Am. Lab. 1990, October, 17-24.
Although there likely are as many descriptions of the analytical approach as there are analytical chemists, it is convenient to define it as the five-step process shown in Figure 1.2.1 .
Three general features of this approach deserve our attention. First, in steps 1 and 5 analytical chemists have the opportunity to collaborate with individuals outside the realm of analytical chemistry. In fact, many problems on which analytical chemists work originate in other fields. Second, the heart of the analytical approach is a feedback loop (steps 2, 3, and 4) in which the result of one step requires that we reevaluate the other steps. Finally, the solution to one problem often suggests a new problem.
Analytical chemistry begins with a problem, examples of which include evaluating the amount of dust and soil ingested by children as an indicator of environmental exposure to particulate based pollutants, resolving contradictory evidence regarding the toxicity of perfluoro polymers during combustion, and developing rapid and sensitive detectors for chemical and biological weapons. At this point the analytical approach involves a collaboration between the analytical chemist and the individual or agency working on the problem. Together they determine what information is needed and clarify how the problem relates to broader research goals or policy issues, both essential to the design of an appropriate experimental procedure.
These examples are taken from a series of articles, entitled the “Analytical Approach,” which for many years was a regular feature of the journal Analytical Chemistry.
To design the experimental procedure the analytical chemist considers criteria, such as the required accuracy, precision, sensitivity, and detection limit, the urgency with which results are needed, the cost of a single analysis, the number of samples to analyze, and the amount of sample available for analysis. Finding an appropriate balance between these criteria frequently is complicated by their interdependence. For example, improving precision may require a larger amount of sample than is available. Consideration also is given to how to collect, store, and prepare samples, and to whether chemical or physical interferences will affect the analysis. Finally a good experimental procedure may yield useless information if there is no method for validating the results.
The most visible part of the analytical approach occurs in the laboratory. As part of the validation process, appropriate chemical and physical standards are used to calibrate equipment and to standardize reagents.
The data collected during the experiment are then analyzed. Frequently the data first is reduced or transformed to a more readily analyzable form and then a statistical treatment of the data is used to evaluate accuracy and precision, and to validate the procedure. Results are compared to the original design criteria and the experimental design is reconsidered, additional trials are run, or a solution to the problem is proposed. When a solution is proposed, the results are subject to an external evaluation that may result in a new problem and the beginning of a new cycle.
Chapter 3 introduces you to the language of analytical chemistry. You will find terms such accuracy, precision, and sensitivity defined there. Chapter 4 introduces the statistical analysis of data. Calibration and standardization methods, including a discussion of linear regression, are covered in Chapter 5. See Chapter 7 for a discussion of how to collect, store, and prepare samples for analysis. See Chapter 14 for a discussion about how to validate an analytical method.
As noted earlier some scientists question whether the analytical approach is unique to analytical chemistry. Here, again, it helps to distinguish between a chemical analysis and analytical chemistry. For an analytically-oriented scientist, such as a physical organic chemist or a public health officer, the primary emphasis is how the analysis supports larger research goals that involve fundamental studies of chemical or physical processes, or that improve access to medical care. The essence of analytical chemistry, however, is in developing new tools for solving problems, and in defining the type and quality of information available to other scientists.
As an exercise, let’s adapt our model of the analytical approach to the development of a simple, inexpensive, portable device for completing bioassays in the field. Before continuing, locate and read the article
“Simple Telemedicine for Developing Regions: Camera Phones and Paper-Based Microfluidic Devices for Real-Time, Off-Site Diagnosis”
by Andres W. Martinez, Scott T. Phillips, Emanuel Carriho, Samuel W. Thomas III, Hayat Sindi, and George M. Whitesides. You will find it on pages 3699-3707 in Volume 80 of the journal Analytical Chemistry, which was published in 2008. As you read the article, pay particular attention to how it emulates the analytical approach and consider the following questions:
- What is the analytical problem and why is it important?
- What criteria did the authors consider in designing their experiments? What is the basic experimental procedure?
- What interferences were considered and how did they overcome them? How did the authors calibrate the assay?
- How did the authors validate their experimental method?
- Is there evidence that steps 2, 3, and 4 in Figure 1.2.1 are repeated?
- Was there a successful conclusion to the analytical problem?
Don’t let the technical details in the paper overwhelm you; if you skim over these you will find the paper both well-written and accessible.
What is the analytical problem and why is it important?
A medical diagnoses often relies on the results of a clinical analysis. When you visit a doctor, they may draw a sample of your blood and send it to the lab for analysis. In some cases the result of the analysis is available in 10-15 minutes. What is possible in a developed country, such as the United States, may not be feasible in a country with less access to expensive lab equipment and with fewer trained personnel available to run the tests and to interpret the results. The problem addressed in this paper, therefore, is the development of a reliable device for rapidly performing a clinical assay under less than ideal circumstances.
What criteria did the authors consider in designing their experiments?
In considering a solution to this problem, the authors identify seven important criteria for the analytical method: (1) it must be inexpensive; (2) it must operate without the need for much electricity, so that it can be used in remote locations; (3) it must be adaptable to many types of assays; (4) its must not require a highly skilled technician; (5) it must be quantitative; (6) it must be accurate; and (7) it must produce results rapidly.
What is the basic experimental procedure?
The authors describe how they developed a paper-based microfluidic device that allows anyone to run an analysis simply by dipping the device into a sample (synthetic urine, in this case). The sample moves by capillary action into test zones containing reagents that react with specific species (glucose and protein, for this prototype device). The reagents react to produce a color whose intensity is proportional to the species’ concentration. A digital photograph of the microfluidic device is taken using a cell phone camera and sent to an off-site physician who uses image editing software to analyze the photograph and to interpret the assay’s result.
What interferences were considered and how did they overcome them?
In developing this analytical method the authors considered several chemical or physical interferences. One concern was the possibility of non-specific interactions between the paper and the glucose or protein, which might lead to non-uniform image in the test zones. A careful analysis of the distribution of glucose and protein in the text zones showed that this was not a problem. A second concern was the possibility that particulate materials in the sample might interfere with the analyses. Paper is a natural filter for particulate materials and the authors found that samples containing dust, sawdust, and pollen do not interfere with the analysis for glucose. Pollen, however, is an interferent for the protein analysis, presumably because it, too, contains protein.
How did the author’s calibrate the assay?
To calibrate the device the authors analyzed a series of standard solutions that contained known concentrations of glucose and protein. Because an image’s intensity depends upon the available light, a standard sample is run with the test samples, which allows a single calibration curve to be used for samples collected under different lighting conditions.
How did the author’s validate their experimental method?
The test device contains two test zones for each analyte, which allows for duplicate analyses and provides one level of experimental validation. To further validate the device, the authors completed 12 analyses at each of three known concentrations of glucose and protein, obtaining acceptable accuracy and precision in all cases.
Is there any evidence of repeating steps 2, 3, and 4 in Figure 1.2.1?
Developing this analytical method required several cycles through steps 2, 3, and 4 of the analytical approach. Examples of this feedback loop include optimizing the shape of the test zones and evaluating the importance of sample size.
Was there a successful conclusion to the analytical problem?
Yes. The authors were successful in meeting their goals by developing and testing an inexpensive, portable, and easy-to-use device for running clinical samples in developing countries.
This exercise provides you with an opportunity to think about the analytical approach in the context of a real analytical problem. Practice exercises such as this provide you with a variety of challenges ranging from simple review problems to more open-ended exercises. You will find answers to practice exercises at the end of each chapter.
Use this link to access the article’s abstract from the journal’s web site. If your institution has an on-line subscription you also will be able to download a PDF version of the article.