**5. Major challenges**

108 Analytical Chemistry

pure analytes).

Figure 3).

products or the environment.

also known as "ideal analytical quality".

*1. True information* corresponds to intrinsic information about objects or systems. It is subject to no uncertainty and hence equivalent to trueness, which is unavailable to analysts. It is

2. *Referential information* corresponds to the highest quality level that can be achieved in practice, with the information about a certified reference material (CRM) as the most typical example. Referential information is usually obtained in interlaboratory exercises where nonroutine laboratories analyze the same sample under the supervision of a renown organization (e.g. NIST in USA). Certified reference materials and their associated values are essential with a view to assuring quality in analytical methods and their results. The main problem here is their limited availability. In fact, only 3–5% of current needs for CRMs in (bio)chemical analysis have been met, in clear contrast with up to 90–95% in Metrology in Physics. Under these conditions, analysts are very often compelled to use alternative strategies to validate new analytical methods (e.g. standard addition procedures involving

3. *Routine information* is that produced by control laboratories or on-site systems operating outside the laboratory and largely used to control the quality of foodstuffs, industrial

*4. Required information* is that demanded by clients to make grounded, timely decisions and constitutes the third basic analytical standard (see Figure 4), which is frequently disregarded despite its high relevance to the major aims and objectives of Analytical Chemistry (see

5. *Perceived information*, which can be of a similar, higher or lower quality than that actually required by the client. Ideally, a client's perceived and required information should coincide. In some cases, the information delivered falls short of that required and can thus be deemed of low quality. Such is the case, for example, with the toxicological characterization of seawater by potential mercury contamination. The total mercury concentration is inadequate for this purpose because the toxicity of mercury species differs with their nature (inorganic, organometallic). It is therefore necessary to provide

The sides of the tetrahedron of Figure 12 represent the relationships between the different types of analytical information [19]. There are two contradictory relationships (forces) arising from delivered analytical information of great significance to Analytical Chemistry, namely: (1) the relationship between required and delivered information (2–4 in Figure 12), which represents problem solving and is related to the second aim of the discipline (see Figure 3); and (2) that between routinely delivered information and referential information (3–4 in Figure 12), which coincide at the highest metrological quality level —the first aim of Analytical Chemistry (Figure 3). One other significant distinction is that between required and perceived information on the client's side. Analytically, the most convenient situation is that where both types of information coincide in their level of quality —even though it is

discriminate information for each potentially toxic mercury species.

desirable that the client's perception surpass the actual requirements.

Achieving the general aims and objectives of Analytical chemistry in today's changing world requires producing tangible (reagents, sorbents, solvents, instruments, analyzers) and intangible means (strategies, calibration procedures, advances in basic science) to facilitate the development of new analytical methods or improvement of existing ones. This, however, is beyond the scope of this section, which is concerned with general trends in this context.

*1. A sound balance between metrological and problem solving approaches for each information demand.* The situation in each case depends strongly on the specific type of information and its characteristics (see Figure 8). With routine information, the challenge is to adopt welldefined quality compromises, which usually involves selecting and adapting analytical processes to fitness for purpose. Obtaining information of a higher scientific–technical level (e.g. that for materials used in R&D&I processes) calls for a high metrological quality level, as well as for exhaustive sample processing and sophisticated laboratory equipment.

*2- Information required from objects/systems far from the ordinary macroscopic dimensions.* These target objects or systems are directly inaccessible to humans because of their location or size. The size of such objects can fall at two very distant ends: nanomatter and outer space.

*Analyzing the nanoworld* is a real challenge for today's and tomorrow Analytical Chemistry. Extracting accurate information from nanostructured matter requires adopting a multidisciplinary approach. Nanotechnological information can be of three types according to nature; all are needed to properly describe and characterize nanomatter. Figure 13 shows the most salient types of physical, chemical and biological information that can be extracted from the nanoworld. Nanometrology, both physical and chemical, is still at an incipient stage of development. There is a current trend to using powerful hybrid instruments affording the almost simultaneous extraction of nanoinformation by using physical (e.g. atomic force microscopy, AFM) and chemical techniques (Raman and FTIR spectroscopies, electrochemistry).

*The extraction of accurate information from objects and systems in outer space* is a challenge at the other end of the "usual" range. This peculiar type of analysis uses miniaturized instruments requiring little maintenance and energy support. There are three different choices in this context, namely: (*a*) remote spectrometric analyses from spacecrafts with, for example, miniaturized X-ray spectrometers [20] or miniaturized mass spectrometers for the analysis of cosmic dust [21]; (*b*) analyses implemented by robots operating on the surface of other planets (e.g. to find traces of water in Mars [22], by using laser ionizationmass spectrometers [23]); or (*c*) monitoring of the inner and outer atmospheres of spacecrafts [ 24,25].

Analytical Chemistry Today and Tomorrow 111

for a new strategy (an intangible R&D&I analytical product according to Figure 5) intended to minimize the negative connotations of conventional sample treatment steps and facilitate the adoption of quality compromises between metrology and problem solving. This strategy uses a combination of vanguard (screening) systems and rearguard (conventional) systems

*Vanguard analytical systems* are in fact sample screening systems (SSS) [27,28] which are used in many activities where information is rapidly needed to make immediate decisions in relation to an analytical problem. Their most salient features are as follows: (*a*) simplicity (*viz.* the need for little or no sample treatment); (*b*) a low cost per sample–analyte pair; (*c*) a rapid response; (*d*) the production of atypical results (binary responses, total indices, method-defined parameters); and (*e*) reliability in the response. These systems act as mere sample filters or selectors and their greatest weakness is the low metrological quality of their responses —however, uncertainties up to 5–15% are usually accepted as a toll for rapidity and simplicity, which are essential and in contradiction with capital analytical properties. Sample screening systems provide a very attractive choice for solving analytical problems involving high frequency information demands. If these systems are to gain widespread, systematic use, they must overcome some barriers regarding accuracy (viz. the absence of false negatives for rapid binary responses), metrological support (traditionally, norms and guides have focused almost exclusively on quantitative data and their uncertainties) and commercial availability (e.g. in the form of dedicated instruments acting as analyzers for determining groups of analytes in a given type of sample such as antioxidants in foodstuffs

*Rearguard analytical systems* are those used to implement conventional analytical processes. Their most salient features are as follows: (*a*) they require conventional, preliminary operations for sample treatment and these involve intensive human participation and are difficult to automate (e.g. dissolution, solid and liquid extraction, solvent changeover); (*b*) they also usually require sophisticated instruments (e.g. GC–MS, GC–MS/MS, GC–FTIR/MS, LC–MS, LC–ICP-MS, CE–MS); (*c*) they afford high accuracy as a result of their excellent sensitivity and selectivity; (*d*) they use powerful primary data processing systems supported by massive databases easily containing 5000 to 50 000 spectra for pure substances, which ensures highly reliable results; (*e*) they usually provide information for each individual target analyte in isolation; and (*f*) they are expensive and operationally slow, but provide

An appropriate combination of these two types of systems allows one to develop *vanguard– rearguard analytical strategies* (see Figure 14). With them, a large number of samples are subjected to the vanguard (screening) system to obtain binary or total index responses in a short time window. The output is named "crash results" and can be used to make immediate decisions. In fact, the vanguard system is used as a sample "filter" or selector to identify a given attribute in a reduced number of samples (e.g. a toxicity level exceeding the limit tolerated by law or by clients) which are subsequently processed systematically with the rearguard analytical system to obtain quantitative data and their uncertainty for each

as illustrated in Figure 14.

or contaminants in water).

information of the highest possible quality level.

**Figure 13.** Types of information that can be extracted from the nanoworld. For details, see text.

*3. Breaking the traditional boundaries of the analytical laboratory.* To be consistent with its present aims and objectives (Figure 3), Analytical Chemistry cannot be exclusively confined inside the laboratory walls. In fact, it is necessary to open laboratory doors and analysts' minds in at least two complementary ways, namely:

(*a*) Analytical Chemistry should play an active role in activities preceding and following the development of analytical processes. Analytical chemists should play a twofold external role here by participating in the design and control of sampling procedures, and also in the discussion and interpretation of analytical results with other professionals in a multidisciplinary approach to transforming information (results) into knowledge (reports).

(*b*) Analytical Chemistry is increasingly focusing on the production of primary data from (automated) analytical processes implemented with so named "on site" systems outside the laboratory. These systems accumulate or send the requested primary data or results to a central laboratory. In the industrial field, on site monitoring can be performed "in-line" or "on-line". In clinical analysis, points of care testing systems (POCTs) [15] are extensively used for this purpose. The development of robust, reliable sensors for a broad range of analytes in a variety of sample types is a major challenge in this context, where automated calibration and quality control are the two greatest weaknesses.

*4. Vanguard–rearguard analytical strategies* [26]. As can be seen from Figure 9, the demand for (bio)chemical information has grown dramatically in the past decade and will continue to grow in the next. As a consequence, conventional analytical laboratories have been rendered unable to accurately process large numbers of samples each day. This has raised the need for a new strategy (an intangible R&D&I analytical product according to Figure 5) intended to minimize the negative connotations of conventional sample treatment steps and facilitate the adoption of quality compromises between metrology and problem solving. This strategy uses a combination of vanguard (screening) systems and rearguard (conventional) systems as illustrated in Figure 14.

110 Analytical Chemistry

spacecrafts [ 24,25].

surface of other planets (e.g. to find traces of water in Mars [22], by using laser ionizationmass spectrometers [23]); or (*c*) monitoring of the inner and outer atmospheres of

**Figure 13.** Types of information that can be extracted from the nanoworld. For details, see text.

minds in at least two complementary ways, namely:

calibration and quality control are the two greatest weaknesses.

*3. Breaking the traditional boundaries of the analytical laboratory.* To be consistent with its present aims and objectives (Figure 3), Analytical Chemistry cannot be exclusively confined inside the laboratory walls. In fact, it is necessary to open laboratory doors and analysts'

(*a*) Analytical Chemistry should play an active role in activities preceding and following the development of analytical processes. Analytical chemists should play a twofold external role here by participating in the design and control of sampling procedures, and also in the discussion and interpretation of analytical results with other professionals in a multidisciplinary approach to transforming information (results) into knowledge (reports).

(*b*) Analytical Chemistry is increasingly focusing on the production of primary data from (automated) analytical processes implemented with so named "on site" systems outside the laboratory. These systems accumulate or send the requested primary data or results to a central laboratory. In the industrial field, on site monitoring can be performed "in-line" or "on-line". In clinical analysis, points of care testing systems (POCTs) [15] are extensively used for this purpose. The development of robust, reliable sensors for a broad range of analytes in a variety of sample types is a major challenge in this context, where automated

*4. Vanguard–rearguard analytical strategies* [26]. As can be seen from Figure 9, the demand for (bio)chemical information has grown dramatically in the past decade and will continue to grow in the next. As a consequence, conventional analytical laboratories have been rendered unable to accurately process large numbers of samples each day. This has raised the need *Vanguard analytical systems* are in fact sample screening systems (SSS) [27,28] which are used in many activities where information is rapidly needed to make immediate decisions in relation to an analytical problem. Their most salient features are as follows: (*a*) simplicity (*viz.* the need for little or no sample treatment); (*b*) a low cost per sample–analyte pair; (*c*) a rapid response; (*d*) the production of atypical results (binary responses, total indices, method-defined parameters); and (*e*) reliability in the response. These systems act as mere sample filters or selectors and their greatest weakness is the low metrological quality of their responses —however, uncertainties up to 5–15% are usually accepted as a toll for rapidity and simplicity, which are essential and in contradiction with capital analytical properties. Sample screening systems provide a very attractive choice for solving analytical problems involving high frequency information demands. If these systems are to gain widespread, systematic use, they must overcome some barriers regarding accuracy (viz. the absence of false negatives for rapid binary responses), metrological support (traditionally, norms and guides have focused almost exclusively on quantitative data and their uncertainties) and commercial availability (e.g. in the form of dedicated instruments acting as analyzers for determining groups of analytes in a given type of sample such as antioxidants in foodstuffs or contaminants in water).

*Rearguard analytical systems* are those used to implement conventional analytical processes. Their most salient features are as follows: (*a*) they require conventional, preliminary operations for sample treatment and these involve intensive human participation and are difficult to automate (e.g. dissolution, solid and liquid extraction, solvent changeover); (*b*) they also usually require sophisticated instruments (e.g. GC–MS, GC–MS/MS, GC–FTIR/MS, LC–MS, LC–ICP-MS, CE–MS); (*c*) they afford high accuracy as a result of their excellent sensitivity and selectivity; (*d*) they use powerful primary data processing systems supported by massive databases easily containing 5000 to 50 000 spectra for pure substances, which ensures highly reliable results; (*e*) they usually provide information for each individual target analyte in isolation; and (*f*) they are expensive and operationally slow, but provide information of the highest possible quality level.

An appropriate combination of these two types of systems allows one to develop *vanguard– rearguard analytical strategies* (see Figure 14). With them, a large number of samples are subjected to the vanguard (screening) system to obtain binary or total index responses in a short time window. The output is named "crash results" and can be used to make immediate decisions. In fact, the vanguard system is used as a sample "filter" or selector to identify a given attribute in a reduced number of samples (e.g. a toxicity level exceeding the limit tolerated by law or by clients) which are subsequently processed systematically with the rearguard analytical system to obtain quantitative data and their uncertainty for each

target analyte. The rich information thus obtained can be used for three complementary purposes, namely: (1) to confirm the crash results of vanguard systems (e.g. positives in binary responses to ensure that they are correct); (2) to amplify the simple (bio)chemical information provided by vanguard systems and convert global information about a group of analytes into discriminate information for each for purposes such as determining relative proportions; and (3) to check the quality of vanguard systems by using them to process a reduced number of randomly selected raw samples according to a systematic sampling plan.

Analytical Chemistry Today and Tomorrow 113

**SRAC** Social Responsibility of Analytical Chemistry

**NIST** National Institute of Standards and Technology (USA)

**GC-MS** Gas Chromatography – Mass Spectrometry coupling

**LC-MS** Liquid Chromatography – Mass Spectrometry coupling

**CE-MS** Capillary Electrophoresis – Mass Spectrometry coupling

has been supported by grant CTQ2011-23790 of the Spanish Government.

(2nd edition). 2004, *Wiley-VCH*, Weinheim, Germany.

problem solving". *Trends Anal. Chem.* 2004, *23*, 527–534.

products and their use in practice". *Analyst*. 2007, *132*, 97–100.

*Chim. Acta.* 1999, *400*, 425–432.

*Chem.* 1993, *65*, 781A-787A.

*Quím*. 2011, 107(1), 58–68.

**GC-MS/MS** Gas Chromatography – Mass Spectrometry / Mass Spectrometry coupling **GC-FTIR/MS** Gas Chromatography – Fourier Transform Infrared Spectroscopy / Mass

**LC-ICP-MS** Liquid Chromatography – Inductively Coupled Plasma Spectrometry – Mass

The topic dealt with in this chapter was the subject of the author's lecture in his investiture as Doctor Honoris Causa by the University of Valencia (Spain) on March 30, 2011. This work

[2] R. Kellner, J.M. Mermet, M. Otto, H.D. Widmer, M. Valcárcel "Analytical Chemistry"

[3] M. Valcárcel "Principles of Analytical Chemistry". 2000, *Springer–Verlag*, Heidelberg, pp

[4] M. Valcárcel, B. Lendl "Analytical Chemistry at the interface between metrology and

[5] M. Valcárcel, A. Ríos "Reliability of analytical information in the XXIst century". *Anal.* 

[6] M. Valcárcel, B.M. Simonet, S. Cárdenas "Bridging the gap between analytical R&D

[7] M. Valcárcel, A. Ríos "The hierarchy and relationships of analytical properties". *Anal.* 

[8] M. Valcárcel, E. Aguilera-Herrador "La información (bio)química de calidad". *An.* 

[1] R. Murray. "The permanency of fading boundaries" *Anal. Chem.*, 1996, 68, 457A.

**CRM** Certified Reference Material

Spectrometry coupling

Spectrometry coupling

*Faculty of Sciences of the University of Córdoba, Spain* 

**Author details** 

Miguel Valcárcel

**6. References** 

1–35.

**Acknowledgement** 

**AFM** Atomic Force Microscopy **POCTs** Point-of-Care-Testing **SSS** Sample Screening Systems

**Figure 14.** Vanguard–rearguard analytical strategies for the systematic analysis of large numbers of samples. For details, see text.

## **List of acronyms**



#### **Author details**

112 Analytical Chemistry

plan.

samples. For details, see text.

**R&D&I** Research, Development and Innovation

**FTIR** Fourier Transform Infrared Spectroscopy

**PAHs** Polycyclic Aromatic Hydrocarbons

**PCBs** Polychlorinated Biphenyls **MDPs** Method Defined Parameters

**SR** Social Responsibility

**ISO** International Organization for Standardization

**List of acronyms** 

target analyte. The rich information thus obtained can be used for three complementary purposes, namely: (1) to confirm the crash results of vanguard systems (e.g. positives in binary responses to ensure that they are correct); (2) to amplify the simple (bio)chemical information provided by vanguard systems and convert global information about a group of analytes into discriminate information for each for purposes such as determining relative proportions; and (3) to check the quality of vanguard systems by using them to process a reduced number of randomly selected raw samples according to a systematic sampling

**Figure 14.** Vanguard–rearguard analytical strategies for the systematic analysis of large numbers of

Miguel Valcárcel *Faculty of Sciences of the University of Córdoba, Spain* 
