Feature

pubs.acs.org/ac

Present and Future Challenges in Food Analysis: Foodomics

The state-of-the-art of food analysis at the beginning of the 21st century is presented in this work,
together with its major applications, current limitations, and present and foreseen challenges.
Virginia García-Cañas,† Carolina Simó,† Miguel Herrero, Elena Ibáñez, and Alejandro Cifuentes*
Laboratory of Foodomics, CIAL (CSIC), Nicolas Cabrera 9, 28049 Madrid, Spain

*
S Supporting Information

had a major impact on food laboratories. Consequently, more

powerful, cleaner and cheaper analytical procedures are now
sought by food chemists, regulatory agencies, and quality
control laboratories. These demands have increased the need
for more sophisticated instrumentation and more appropriate
methods able to offer better qualitative and quantitative results
while increasing the sensitivity, precision, specificity, and/or
speed of analysis.2
Apart from these essential considerations, there are also a
large number of food properties for which analytical chemistry
will play a crucial role. Just to mention a few, the identification
of the effect of food production, processing, preparation, and
use on nutrient content, toxic contaminant generation, and
inactivation of naturally occurring toxins; the compliance with
food and trade laws ensuring food safety and traceability; the
detection of adulteration and product tampering; the character-
ization of chemical composition of foods; the study of food
rheology, morphology, structure or surface; the analysis of
physical, physicochemical, thermal, or microbiological properties;
the evaluation of sensory characteristics, etc. These properties

■
will have a critical influence on food safety, quality, processing,
and acceptance.3
FOOD ANALYSIS: THE BASIS Currently, there is also a general trend in food science to link
The development and application of analytical methods and food and health. Thus, food is considered today not only a
techniques in food science has grown parallel to the consumers source of energy but also an affordable way to prevent future
concern about what is in their food and the safety of the food diseases. The number of opportunities (e.g., new methodologies,
they eat. To give an adequate answer to the raising consumers’ new generated knowledge, new products, etc.) derived from this
demands, food analysts have to face increasingly complex chal- trend are impressive and it includes, e.g., the possibility to
lenges that require using the best available science and technology. account for food products tailored to promote the health and
A good portion of this complexity is due to the so-called global- well-being of groups of population identified on the basis of their
ization and the movement of food and related raw materials individual genomes. The introduction in this area of research of
worldwide, which are generating contamination episodes that are advanced “omics” approaches such as Foodomics4 have made it
becoming also global. An additional difficulty is that many pro- possible that food scientists can face problems unthinkable a few
ducts contain multiple and processed ingredients, which are often years ago. However, to achieve these goals, researchers involved
shipped from different parts of the world, and share common in modern food science need an adequate background on
storage spaces and production lines. As a result, ensuring the advanced analytical tools in order to extract all the potential from
safety, quality, and traceability of food has never been more these new methodologies. Usually, a sine qua non condition is to
complicated and necessary than today.1 work within multidisciplinary teams in order to be able to face
The first goal of food analysis has traditionally been, and still the huge complexity of the problem and to handle the generated
is, to ensure food safety. To meet this goal, food laboratories results in a rational way.
are being pushed to exchange their classical procedures for Thus, food analysis is, nowadays, one of the most important
modern analytical techniques that allow them to give an ade- application areas of analytical chemistry. In this work, the main
quate answer to this global demand. Besides, the new European analytical techniques employed in food analysis at the beginn-
regulations in the EU countries (e.g., Regulation EC 258/97 or ing of the 21st century will be presented together with their
EN 29000 and subsequent issues), the Nutrition Labeling
and Education Act in the U.S., and the Montreal Protocol have Published: September 7, 2012

© 2012 American Chemical Society 10150 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159
Analytical Chemistry Feature

Figure 1. Sample preparation, biological, spectroscopic, and separation techniques used in food analysis and the number of citations in the FSTA
database in the period 2001−2011. Within biological techniques, the group “others” includes radioimmunoassay and enzymatic analysis. The group
“others” in spectroscopic techniques includes Raman (402), electron spin resonance (366), dielectric spectroscopy (57), refractometry (54),
polarimetry (38), chemiluminiscence (15), and photoacustic (0).

main application areas and current difficulties, concluding with Technology Abstracts (FSTA) using as key terms the names of
an outlook on some anticipated future challenges. the analytical technique indicated in each case. There are some

■
important issues that can be concluded from Figures 1 and 2
ANALYTICAL CHEMISTRY AND FOOD ANALYSIS when they are compared to similar figures published by our
IN THE 21ST CENTURY group at the end of the 20th century summarizing the works
published on food analysis in the period 1990−2000.5 The
A description of the huge number of analytical techniques most important trend is the huge increase in biological and
commonly used in food analysis is out of the scope of this work.
sample preparation techniques as compared with the previous
Just to mention a few, analytical techniques typically used in
period and the important decrease in the use of radiochemical
food analysis can be classified as (i) spectroscopic as mass spec-
and thermal techniques, probably due to the specific informa-
trometry (MS), nuclear magnetic resonance (NMR), infrared
tion that those techniques provide and the need for high-
(IR), atomic spectroscopy (AS), fluorescence, etc.; (ii) bio-
logical as polymerase chain reaction (PCR), immunological throughput techniques widely based on new and advanced
techniques, biosensors, etc.; (iii) separation as high-perform- technologies able to provide more information of better quality.
ance liquid chromatography (HPLC), gas chromatography Thus, it is not strange that techniques such as thermal and radio-
(GC), capillary electrophoresis (CE), supercritical fluid chro- chemical have decreased by half (compared to the previous
matography (SFC), etc.; (iv) sample preparation as solid phase period), and others such as spectroscopic, biological, and sample
extraction (SPE), supercritical fluid extraction (SFE), head- preparation techniques have increased 2, 3, and 4 times,
space (HS), flow injection analysis (FIA), purge and trap respectively. Other well established techniques such as separation
(PAT), pressurized liquid extraction (PLE), microwave assisted techniques continue to be used to a high extent, but nowadays
extraction (MAE), automatic thermal desorption (ATD), etc.; they are not the most widely used (as in the period 1990−2000),
(v) electrochemical; (vi) hyphenated techniques, etc. The number since spectroscopic techniques have gained importance and are
of techniques in food analysis is even higher if the subdisciplines at present the most extensively used in food analysis. In fact, the
under the above techniques are considered. detection and content of a number of food constituents, as well
To help summarize the large number of analytical techniques as the study of food properties, may be achieved by measuring
used and topics addressed in food analysis, Table S-1 is in- the interaction of electromagnetic radiation (absorption in the
cluded as Supporting Information to describe all the works visible, infrared, fluorescence, Raman, etc.) with food. Thanks
published in the last 3 years (i.e., 2009−2011) as review papers, to new instrumental developments of spectroscopic techniques
books, and book chapters (more than 160) on different food together with multivariate chemometric methods, which are appro-
analysis subjects. Moreover, Figures 1 and 2 provide informa- priate and useful for the evaluation of fluorescence or infrared
tion on the number of works published in the period 2001− spectra exhibiting slight differences such as the ones recorded on
2011 found through a search in the database Food Science and food products, it has been possible to develop prediction models.
10151 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159
Analytical Chemistry Feature

Figure 2. Electrochemical, rheological, radiochemical, and thermal techniques used in food analysis and the number of citations in the FSTA
database in the period 2001−2011.

Recently, imaging technology such as confocal laser scanning PCR a widely used technique worldwide and can be found in
microscopy or hyperspectral imaging coupled to image analysis almost all laboratories working in food analysis.
techniques has successfully been used to study highly As for the distribution and importance of the separation
heterogeneous food products. Indeed, image analysis techniques techniques, LC and CE applications have raised mainly due to
such as mathematical morphology or image texture analysis make the new developments for reducing analysis time while keeping
it possible to quantify structures in the images and to show resolution and efficiency (UPLC, on-chip CE, monolithic
the influence of different manufacturing processes on the protein columns), the new separation mechanisms (HILIC, etc.), and
network microstructure of foods.6 On the other hand, the the use of MS as a routine detector for LC and CE. On the
important increase in the use of spectroscopic techniques in food other hand, GC is keeping similar numbers as previously seen,
analysis might be due to the high number of new applications of showing its importance for certain applications. Lastly, the
NMR, fluorescence, IR, etc. that can be, in the case of NMR, important increase in hyphenated separation techniques as
attributed to the need for unambiguous identification of un- heart-cutting multidimensional approaches (e.g., LC−LC, GC−
known compounds with biological properties, metabolites, etc., GC, LC−GC, LC−CE) or comprehensive two-dimensional
which probably has contributed to the implementation of this techniques (LC × LC, GC × GC) supports the theory that
technique with numbers quite close to well established techniques more information is needed to be able to decipher the wide
such as fluorescence or even MS. complexity of food samples and their real effects in human
Not surprising is the huge increment in the use of biological health. In fact, multidimensional chromatography has become
techniques; these techniques, based on the use of living organ- an interesting alternative to analyze complex samples also in
isms or some of their products such as enzymes, antibodies, food analysis in a situation in which technological improve-
DNA, etc. to identify and analyze foods, have multiplied by 3 in ments, such as new column technologies, seem to be reaching
their use in food analysis; one technique, PCR, constitutes 60% their maximum level. Thus, peak capacity enhancement achiev-
of the total applications in biological techniques being around able by multidimensional chromatography is by far higher than
double of the total number of biological techniques used in the the obtained after improving by any mean one-dimensional
previous period. This huge increase in the use of PCR can be separations. Multidimensional chromatography allows combi-
attributed to the different steps taken to overcome some of the nation of two or more independent or nearly independent
main difficulties of the technique, related to the quality and separation steps, increasing significantly the separation power of
amount of DNA extracted; at present, new instruments and new the corresponding one-dimensional techniques and, therefore,
standardized protocols, for an important number of samples, make the physical separation of compounds in complex samples.
10152 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159
Analytical Chemistry Feature

Although the coupling between different chromatographic sepa- has also seen an important growing in food analysis, since chiral
rations is not new, the technological development has led, methods can be used to study and characterize foods and
above all, to the increase of comprehensive applications in beverages through the enantiomeric separation of different food
which the whole sample is analyzed in two different, indepen- compounds such as amino acids, pesticides, polyphenols, etc.12
dent dimensions, reducing the sample preparation steps. The Another example is the investigation of food texture in which
number of applications regarding the use of such compre- physical characteristics perceived by the senses are investigated.
hensive techniques increases every year also in the food analysis Research in this area has evolved tremendously in the past
domain, and it is expected to keep growing.7 decade based on multidisciplinary approaches that encompass
Special attention has to be also paid to the important chemistry, physics, physiology, and psychology, to study the
(around 4 times) increase in the use of sample preparation fracture of food, the sounds it makes during biting and chew-
techniques in food analysis. Advances in sample preparation ing, its microstructure, muscle movements during mastication,
aim to minimize laboratory solvent use and hazardous waste swallowing, and acceptability, etc.13 The determination of con-
production, save employee labor and time, and reduce the cost taminants in foods is a must for ensuring that human exposure
per sample, while improving the efficiency of the analyte isola- to noxious residues through diet does not exceed acceptable
tion. At present, new green sample preparation methods such levels for health. Consequently, robust analytical methods are
as SFE and subcritical water extraction (SWE, also called continuously under development in order to improve recovery
accelerated solvent extraction) are among the more promising rates, quantification limits, time of analysis, or to reduce matrix
processes in food science, not only in food analysis but also for effects.14 Interestingly, nowadays, method validation is also
obtaining new functional food ingredients.8 These extraction required for carrying out both research and monitoring programs
techniques based on pressurized fluids provide higher selectivities and thus for defining limitations and supporting enforcement of
and shorter extraction times and are environmentally-friendly. The regulations.15 Additional applications of analytical chemistry
total numbers for these techniques in the period 2001−2011 methods related to food analysis in the food industry to include
reached over 1500 publications, compared to around 300 at the the monitoring of critical points in the food production/
end of 20th century; one interesting example is, for instance, PLE, manipulation chain, the analytical control of processes in the
which did not appear in the previous period and is nowadays the food industry, the development of fast and in-line screening tests,
second more important “green” sample preparation technique the validation schemes for the transfer of research methods to
used in food analysis, only surpassed by SFE. Also, different modes routine laboratories, etc.
of liquid-phase microextraction (LPME) such as single drop It is also noteworthy to describe how MS has evolved in the
microextraction, dispersive liquid−liquid microextraction, and last years in food analysis. During the past decade, MS has
hollow fiber-LPME are being increasingly applied for the extrac- tended to be used largely for direct identification and quanti-
tion of both inorganic and organic analytes from different matrixes fication of food compounds typically coupled to other separa-
in food analysis, due to their advantages over conventional tion techniques like LC and, to a less extent, CE. Single quadrupole
extraction procedures in terms of simplicity, effectiveness, rapidity, MS has been restricted to screening purposes since these
and low consumption of organic solvents.9 Another important instruments do not meet the more recent criteria set by the EU,
observation, when comparing the numbers and distribution of especially those regarding the requested number of identi-
sample preparation and separation techniques, is the increasing use fication points. As a result, tandem-MS has become a general
of SPE that somehow runs parallel to the use of liquid chromato- tool for identification and quantification of analytes (mainly
graphy for which new separation mechanisms, new applications, contaminants) in food analysis. The enhanced selectivity afforded
and new approaches have been developed in these last 10 years. It by tandem-MS detection may also contribute to the simplification
is interesting also to observe that the number of applications of, for of the extraction procedure, if attention is paid to ion suppression
instance, SPME have come close to other well-established tech- phenomena. At this point, the use of triple quadrupole, ion trap,
niques such as headspace; the expansion of SPME since the last and more recently time-of-flight MS analyzers coupled to uni- or
period considered can be understood due to the easiness of use, bidimensional separation techniques have been widely reported in
the huge range of applicability of fibers and coatings, and the the scientific literature in food analysis.16 It is expected that new
new modalities developed that have widened the range of developments on ionization techniques prior to MS analysis can
applicability.10 make even broader its application in food analysis including new
Other more specific application areas in food analysis have omics applications.17 Proteomics and metabolomics represent
also seen a great development as a result of the combination of powerful analytical platforms to acquire more detailed and com-
several analytical advances that have been put together. This is plete information on food composition even beyond the tradi-
the case of the analysis of the volatile fraction of foods, which is tional food component analysis. This comprehensive knowledge
known to have a crucial effect on food quality and acceptance. of biochemical composition of foods will provide a better under-
The study of the volatile fraction of food or beverage requires standing of metabolic networks allowing the food research com-
analytical methods and technologies able not only to evaluate munity a better insight of the molecular basis of important food
its composition exhaustively but also to monitor variations of its characteristics such as flavor, color, texture, aroma, addedvalue
profile and to detect trace components characterizing the food nutrition, etc.18 In this context, metabolomics (via GC/MS,
being investigated. The strategies of analysis have changed LC−MS, CE−MS, or NMR) has potential to add significant
significantly over the last 15−20 years because of the intro- value to crop and food science, raw material quality and safety,
duction of new approaches, in particular (i) solventless sample food storage, shelf life and postharvest processing.19 The ability
preparation techniques; (ii) fast GC and related techniques; of different transcriptomic, proteomic, and metabolomic
(iii) new analytical techniques, such as comprehensive GC; (iv) approaches has already been shown to assess food safety and
new operative strategies based on approaches developed for other quality at every stage of production to ensure food safety for
fields and applied to food analysis; and (v) data elaboration human consumption.20 They are also valuable tools to dis-
strategies producing a higher level of information.11 Chiral analysis tinguish between similar food products and to detect food frauds
10153 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159
Analytical Chemistry Feature

(adulteration, origin, authenticity, etc.), food-borne pathogens, interferences or food processing, which may not influence
toxic species, food allergens, etc. For instance, in the context of allergenicity but do impair allergen detection.
food safety, several DNA microarray chips have already been Miniaturization of analytical systems will remain under devel-
developed for the detection of food-borne pathogens, toxigenic opment including newly emerging technologies able to offer
microorganisms, genetically modified (GM) organisms analysis, platforms with greater automation and multiplexing capabilities
etc. Proteomic and metabolic changes also occur during crops than traditional biological binding assays. These multiplexed
growing conditions, food processing/preparation (fermentation, bioanalytical techniques are expected to provide control agencies
baking, boiling, etc.), food conservation/storage (freezing, smok- and food industries with new possibilities for improved, more
ing, drying, etc.). These tools have already been demonstrated to efficient monitoring of food and environmental contaminants. In
be very useful for getting a deeper understanding of molecular this regard, developments in planar-array and suspension-array
details of foods and food related matrixes,21 including the analysis technologies have demonstrated their potential in detecting
of GM foods.20 In this later case, the use of omics approaches able pathogens, food allergens and adulterants, toxins, antibiotics, and
to provide useful fingerprints of GM foods (e.g., for GM detec- environmental contaminants.26 In this context, microfluidics
tion, composition monitoring, traceability, study of unintended technology has also shown interesting applications for food ana-
modifications, labeling issues) has already been recommended by lysis, although more effort has to be put on the development of
the European Food Safety Authority.22 multipurpose microfluidic platforms that integrate multiple unit

■ PRESENT AND FUTURE CHALLENGES IN FOOD

ANALYSIS
operations for real food sample analysis.27 Miniaturized systems
and their applications are expected to keep growing in food
analysis.
In spite of the huge number of analytical developments and Regarding multidimensional chromatography methods, from
applications seen in food analysis, there are still a good number a technical point of view, some problems inherent to the con-
of issues that need to be improved in this hot area of research. nection of the two systems still persist, for instance related to
For instance, still hundreds of foodborne infection cases occur the relatively costly operation conditions in GC × GC or the
around the world, and up to one-third of the population in loss in sensitivity in LC × LC. In the coming years, new
industrialized nations suffers from foodborne illness each year. solutions should appear in order to facilitate these couplings as
Regarding pathogens detection in foods, microbiologists have well as to further increase the orthogonality of the systems and,
developed over the last decades reliable culture-based tech- consequently, their separation power and applications in food
niques. Although these methods are considered to be the “gold- analysis. Keeping the cost of analysis as low as possible should
standard”, they remain cumbersome and time-consuming. The also be a priority when designing efficient and new comprehen-
introduction of genetic-based technologies made feasible devel- sive GC and SFC modulators. Besides, the development of
oping sensitive and specific screening tests for the detection of online sample preparation steps in multidimensional systems
microbial pathogens. Microarray-based technologies represent can also be expected. Moreover, the extended use of powerful
an advance in nucleic acid testing methods whose main features MS detectors would even more enhance the applications and
include miniaturization, ability to parallelize sample processing, identification power of these techniques in food analysis.7 An
and ease of automation.23 Besides, the high number of genetic important point to consider is that nowadays these multi-
information already available allows reaching a resolution below dimensional techniques require dedicated laboratories, equip-
the species level, being able to discriminate among microbial ment, and highly trained personnel until they can offer simpler
strains, thanks to the careful choice of variable genomic regions. and more rapid analysis.
Despite the advent of these rapid detection methods based on Food-associated viruses are of emerging importance is food
molecular techniques (or immunoassays), it is suggested that analysis as causative agents of gastrointestinal diseases and
reduction and/or elimination of cultural enrichment will be hepatitis. Because of the development of molecular biological
essential in the quest for truly real-time detection methods. As methods, the detection of noroviruses, rotaviruses, hepatitis A
such, there is an important role for the so-called preanalytical viruses, and hepatitis B viruses and other relevant viruses in
sample processing that in this case would include bacterial different food matrixes is now feasible. However, the designated
concentration and purification from the sample matrix as a step methods need to be improved since their efficiency varies con-
preceding detection.24 In this regard, one analytical challenge siderably depending on the method used, the food matrix, and
that still remains in food safety is to present reliable results with the type of virus. Standardized test procedures are needed for a
respect to official guidelines as fast as possible without impairing realistic comparison of the existing methods.28
method properties such as recovery, accuracy, sensitivity, The variety of toxic residues in food is continuously increas-
selectivity, and specificity.15 ing as a consequence of industrial development, new agricul-
More suitable analytical techniques are still required by con- tural practices, environmental pollution, and climate change.
sumer protection and law enforcement for the detection of This increasing is bringing about the development of everyday
allergens in foods. Food allergy is an important issue in food more powerful, sensitive, and fast analytical methodologies able
analysis because minute amounts of the allergen can have to detect emerging contaminants in foodlike industrial organic
critical consequences in sensitized persons, what has brought pollutants, nanomaterials, pharmaceutical residues, antibiotics
about very demanding requirements on hygiene and legal and coccidiostats, or emerging groups of marine biotoxins.29
regulations imposed on the food industry. Immunological methods Nanotechnology and nanomaterials have remarkable poten-
are currently preferred followed by confirmatory methods. The tial to enhance the food supply through novel applications, in-
determination of allergenic proteins by LC and MS has greatly cluding nutrient and bioactive absorption and delivery systems;
advanced in recent years, and it is now frequently used for the microbial, allergen, and contaminant detection and control;
identification and quantitation of food allergens.25 In spite of food packaging properties and performance; and improved
these advances, confirmatory alternatives are still needed able to colors and flavors. On the basis of these multiple applications,
face other additional problems originated, e.g., by food matrix exposure to nanomaterials in the human food chain may occur
10154 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159
Analytical Chemistry Feature

not only through intentional uses in food manufacturing but as the interaction between crops and its pathogens as well as
also via uses in agricultural production and carry over from use physicochemical changes that take place during fruit ripening;41
in other industries. New analytical methods are, therefore, (xi) to fully understand postharvest phenomena through a global
needed to fully detect and characterize nanomaterials approach that links genetic and environmental responses and
incorporated into foods and in other media. Moreover, there identifies the underlying biological networks. In this regard, it is
is also a need for additional toxicology studies on different types expected that the new omics technologies combined with
of nanomaterials to understand how they can affect food systems biology, as proposed by foodomics, can lead postharvest
safety.30 research into a new era.42
Finally, a clear trend is the implementation of green analytical It is now well-known that health is heavily influenced by
chemistry also in food analysis laboratories, understanding green genetics. However, diet, lifestyle, and environment can have a
analytical chemistry as “the use of analytical chemistry techniques crucial influence on the epigenome, gut microbiome and, by
and methodologies that reduce or eliminate solvents, reagents, association, the transcriptome, proteome and, ultimately, the
preservatives, and other chemicals that are hazardous to human metabolome. When the combination of genetics and nutrition/
health or the environment and that may also enable faster and lifestyle/environment is not properly balanced, poor health is a
more energy-efficient analysis without compromising performance result. Foodomics is a major tool for detecting small changes
criteria”. In this definition it is clear that the hazard is to be induced by food ingredient(s) at different expression levels. A
reduced but keeping (or even improving) the analysis in terms of representation of an ideal foodomics strategy to investigate the
performance. Several approaches such as those concerning the effect of food ingredient(s) on a given system (cell, tissue,
greening of sample preparation techniques (with the use of new organ, or organism) is shown in Figure 3. Following this
green solvents, miniaturization, or employment of solventless foodomics strategy, results on the effect of food ingredient(s) at
techniques) and the combination with new (and cleaner) the genomic/transcriptomic/proteomic and/or metabolomic
separation techniques and chemometrics will greatly contribute level are obtained, making possible new investigations at the
to reaching the goals of this new green era.31 molecular level on food bioactivity and its effect on human

■ FOODOMICS. A NEW DISCIPLINE FOR A NEW

FOOD ERA
health. The interest in foodomics also coincides with a clear
shift in medicine and biosciences toward prevention of future
diseases through adequate food intakes and the development of
One of the main challenges in food analysis will be to improve the so-called functional foods. In this regard, it has been
our limited understanding of the roles of food compounds at mentioned that it is probably too early to conclude on the value
the molecular level (i.e., their interaction with genes and their of many substances for health, and the same can apply to other
subsequent effect on proteins and metabolites) for the rational health relationships that are still under study. Thus, foodomics
design of strategies to manipulate cell functions through diet, could help to overcome these limitations. To achieve this goal,
which is expected to have an extraordinary impact on our it will be necessary to carry out more studies to discover more
health. In this context, foodomics has been defined as a new polymorphisms of one nucleotide, to identify genes related to
discipline that studies the food and nutrition domains through complex disorders, to extend the research on new food pro-
the application of advanced omics technologies to improve ducts, and to demonstrate a higher degree of evidence through
consumer’s well-being, health, and confidence.4 Thus, foodo- epidemiological studies based in foodomics that can lead to
mics is presented as a global discipline in which food (including public recommendations. Moreover, in spite of the significant
nutrition), advanced analytical techniques (mainly omics tools), outcomes expected from a global foodomics strategy, practically
and bioinformatics are combined. The development of geno- there are no papers published in the literature in which results
mics, transcriptomics, proteomics, and metabolomics has given from the three expression levels (transcriptomics, proteomics,
rise to extraordinary opportunities for increasing our under- and metabolomics) are simultaneously presented and merged.
standing about different issues that can now be addressed Figure 4 shows the results from a global Foodomics study on
by foodomics. Just to name a few (i) to understand the bio- the chemopreventive effect of dietary polyphenols against
chemical, molecular, and cellular mechanisms that underlie the HT29 colon cancer cells,42 presenting the genes, proteins and
beneficial or adverse effects of certain bioactive food components metabolites identified (after transcriptomic, proteomic, and
following nutrigenomic approaches;32 (ii) to understand the metabolomic analysis) that are involved in the principal
gene-based differences among individuals in response to a biological processes altered in HT29 colon cancer cells after
specific dietary pattern following nutrigenetic approaches;33 (iii) the treatment with rosemary polyphenols. In order to demon-
to know the identity of genes that are involved in the previous strate all its value, foodomics still needs to be translated to
stage to the onset of the disease, and therefore, possible methods or approaches with medicinal impact, e.g., through the
molecular biomarkers;34 (iv) to determine the effect of bioactive so-called personalized nutrition. In this regard, data interpreta-
food constituents on crucial molecular pathways;35 (v) to tion and integration when dealing with such complex systems is
establish the global role and functions of gut microbiome, a topic not straightforward and has been detected as one of the main
that is expected to open an impressive field of research;36 (vi) to bottlenecks.
understand the stress adaptation responses of food-borne In a recent work, a foodomics approach was applied to
pathogens to ensure food hygiene, processing and preservation;37 investigate the effect of dietary polyphenols on two human
(vii) to investigate the use of food microorganisms as delivery leukemia lines, one showing a drug-sensitive phenotype (K562)
systems including the impact of gene inactivation and deletion and another exhibiting a drug-resistant phenotype (K562/R).43
systems;38 (viii) to carry out the investigation on unintended To this aim, a whole-transcriptome microarray together with
effects in genetically modified crops;39 (ix) the comprehensive a MS based nontargeted analytical approach (via capillary
assessment of food safety, quality, and traceability ideally as a electrophoresis−time-of-flight mass spectrometry, CE−TOF
whole;40 (x) to understand the molecular basis of biological MS, and ultrahigh-performance liquid chromatography−time-
processes with agronomic interest and economic relevance, such of-flight mass spectrometry, UPLC−TOF MS) was employed
10155 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159
Analytical Chemistry Feature

Figure 3. Ideal foodomics platform to investigate the health benefits from dietary constituents on a given biological system (cell, tissue, organ, or
organism), including analytical methodologies used and expected outcomes. Modified with permission from ref 42. Copyright 2012 Elsevier.

to carry out transcriptomics and metabolomics analyses, res- knowledge of researchers working in different fields, typically
pectively. Functional enrichment analysis was done using including analytical chemistry, biology/medicine, bioinfor-
Ingenuity Pathway Analysis (IPA) software as a previous step matics, and statistics. Besides, foodomics tools will also have
for a reliable interpretation of transcriptomic and metabolomic to overcome many limitations for optimal implementation in
profiles. The studied dietary polyphenols altered the expression food analysis. For transcriptomics, the high background noise
of ∼1% of the genes covered by the whole transcriptome that hinders the detection of low signals (i.e., low signal-to-noise
microarray in both leukemia cell lines. Overall, differences in ratios) and the efficiency and specificity of the hybridization
the transcriptional induction of a number of genes encoding probes have to be improved in DNA microarrays. New devel-
phase II detoxifying and antioxidant genes as well as differences opments will probably include the establishment of routine data
in the metabolic profiles observed in the two leukemia cell lines analysis methods and increase in the numbers and lengths of
suggest that dietary polyphenols may exert a differential sequence reads as well. It is also expected that the cost of these
chemopreventive effect in leukemia cells with different analyses will continue decreasing in the near future, allowing new
phenotypes. IPA predictions on transcription factor analysis applications and extensive use of these technologies in foodomics
highlighted inhibition of the Myc transcription factor function research.
by dietary polyphenols, which may explain the observed In proteomics, MS alone or combined with 2D-electro-
antiproliferative effect of dietary extract in the leukemia cells. phoresis, liquid chromatography, and capillary electrophoresis
Metabolomics analysis suggested that dietary polyphenols have become the most used methodologies. There is an evident
differently affected the intracellular levels of some metabolites need of developing improved or alternative technologies (e.g.,
in the two leukemia cell sublines. Integration of data obtained protein microarrays) to become into a reality the routine analysis
from transcriptomics and metabolomics platforms was for proteome research, including improvements in the resolution
attempted by overlaying data sets on canonical (defined) of peptides to provide increased protein coverage. Apart from the
metabolic pathways using IPA software. This strategy enabled everyday more sophisticated sample treatments and separation
the identification of several differentially expressed genes in the techniques, MS will remain essential for the systematic investi-
metabolic pathways modulated by dietary polyphenols gation in proteomics. In this sense, conventional mass spectro-
providing more evidence on the effect of these compounds.43 meters are giving way to the more sophisticated and compact mass
In spite of the huge potential of foodomics, it has to be high- spectrometers, most of them hybrid instruments in a combination
lighted the methodological difficulties to carry it out. In fact, the of two or more analyzers. As can be deduced from the low number
approach is not easy and requires a high degree of complementary of proteomic applications in foodomics studies, it is expected that
10156 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159
Analytical Chemistry Feature

Figure 4. Foodomics identification of the genes, proteins, and metabolites involved in the principal biological processes altered in HT29 colon
cancer cells after their treatment with rosemary polyphenols. In red, up-regulated; in green, down-regulated. Modified with permission from ref 42.
Copyright 2012 Elsevier.

new innovations in proteomic technology will help proteomic pro- to address regarding the development and growth of the available
filing to become standard practice also in foodomics. metabolomic-databases since only a small fraction of the total
A great advance in metabolomics is expected with the number of metabolites has been identified and included in the
incorporation of new MS interfaces for which nearly no sample databases so far, with the majority of naturally occurring meta-
preparation is needed17 and the use of MALDI-imaging mass bolites still being unknown. Besides, the scope and range of meta-
spectrometry (MALDI-MSI) to analyze metabolites to proteins bolites within normal and pathophysiological states will require
at both the tissue and the single-cell level, with information that the field of metabolomics make some unifying assumptions
obtaininged regarding the spatial distribution of specific mole- and agree on standards for targeted metabolites and conditions of
cules.44 Improvements to both sample preparation strategies sampling in order to fully realize its potential in the new foodomics
and analytical platforms (including higher sensitivity NMR sys- field.
tems with possibilities for online MS hyphenation) will enhance The challenge in the combination of Foodomics and systems
the relevance of metabolomics in food research. Comprehensive biology is not only at the technological level, as mentioned
multidimensional techniques, such as GC × GC or LC × LC, are above great improvements are being made and expected in the
also a revolutionary improvement in separation techniques whose omics tools, but also on the bioinformatics side (data process-
use is expected to grow in foodomics in the near future. They not ing, clustering, dynamics, integration of the various omics levels,
only provide enhanced resolution and a huge increase in the peak etc.) that will have to progress for systems biology to demon-
number but also an increase in selectivity and sensitivity in com- strate all its potential in the new foodomics discipline.45 In this
parison with conventional separation techniques. Also, capillary regard, much work is still needed to fill the huge gap in the
electrophoretic techniques and their coupling to mass spectrom- knowledge on many cellular processes and how they take place
at different molecular levels.

■
etry (CE−MS) are ideal tools for metabolomics, due to that they
do not require extensive sample preparation, their wide range of
applications, great efficiency and resolution, and low sample ASSOCIATED CONTENT
consumption. Besides, CE−MS allows the identification of highly *
S Supporting Information
polar and charged metabolites that are difficult to separate by Additional information as noted in text. This material is
standard LC or GC methods. Metabolomics has many challenges available free of charge via the Internet at http://pubs.acs.org.
10157 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159
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Feature

AUTHOR INFORMATION (8) Mendiola, J. A.; Herrero, M.; Cifuentes, A.; Ibañez., E. J.
Chromatogr., A 2007, 1152, 234−246.
Corresponding Author (9) Asensio-Ramos, M.; Ravelo-Perez, L. M.; Gonzalez-Curbelo, M.
*E-mail: [email protected]. A.; Hernandez-Borges, J. J. Chromatogr., A 2011, 1218, 7415−7437.
Author Contributions (10) Kataoka, H.; Lord, H. L.; Pawliszyn, J. J. Chromatogr., A 2000,
† 880, 35−62.
These two authors contributed equally to this work.
(11) Bicchi, C.; Cagliero, C.; Rubiolo, P. Flavour Fragrance J. 2011,
Notes 26, 321−325.
The authors declare no competing financial interest. (12) Herrero, M.; Simo, C.; Garcia-Canas, V.; Fanali, S.; Cifuentes, A.
Biographies Electrophoresis 2010, 31, 2106−2114.
́
Virginia Garcia-Cañ as is a Tenured Researcher at the National (13) Tunick, M. H. J. Agric. Food Chem. 2011, 59, 1477−1480.
(14) Pareja, L.; Fernandez-Alba, A. R.; Cesio, V.; Heinzen, H. TrAC,
Research Council of Spain (CSIC) in Madrid. She develops her
Trends Anal. Chem. 2011, 30, 270−291.
scientific activities in the Laboratory of Foodomics. Her activities
(15) LeDoux, M. J. Chromatogr., A 2011, 1218, 1021−1036.
include the development of advanced analytical methods for genomics (16) Mohamed, R.; Guy, P. A. Mass Spectrom. Rev. 2011, 30, 1073−
and transcriptomics in food quality, safety, and food bioactivity studies. 1095.
Carolina Simó is a Tenured Researcher at the National Research (17) Hajslova, J.; Cajka, T.; Vaclavik, L. TrAC, Trends Anal. Chem.
Council of Spain (CSIC) in Madrid (Spain). Her running research 2011, 30, 204−218.
lines include (i) development and application of advanced capillary (18) Agrawal, G. K.; Jwa, N. S.; Rakwal, R. Proteomics 2009, 9, 935−
electromigration techniques, (ii) chiral analysis for food quality 963.
evaluation, and (iii) proteomics and metabolomics, developing new (19) Shepherd, L. V. T.; Fraser, P.; Stewart, D. Bioanalysis 2011, 3,
CE/LC−MS-based approaches. 1143−1159.
(20) García-Cañas, V.; González, R.; Cifuentes, A. TrAC, Trends Anal.
Miguel Herrero is a contracted researcher under the “Ramón y Cajal” Chem. 2004, 23, 637−643.
program at the National Research Council of Spain (CSIC), in (21) Antignac, J. P.; Courant, F.; Pinel, G.; Monteau, F.; Le Bizec, B.
Madrid, Spain. His main research interests are aimed to the study and TrAC, Trends Anal. Chem. 2011, 30, 292−301.
characterization of new functional ingredients including the develop- (22) European Food Safety Agency. Guidance document of the
ment of new advanced extraction and analytical methods to obtain and scientific panel on GMOs for risk assessment of GM plants and derived
characterize interesting food-related compounds. food and feed. EFSA Communications: Parma, Italy, 2006.
(23) Lancova, K.; Dip, R.; Antignac, J. P.; Bizec, B.; le Elliott, C. T.;
Elena Ibáñez is a Full Professor at the Institute of Food Science
Naegeli, H. TrAC, Trends Anal. Chem. 2011, 30, 181−191.
Research (CIAL) from CSIC in Madrid. Her activity includes the (24) Dwivedi, H. P.; Jaykus, L. A. Crit. Rev. Microbiol. 2011, 37, 40−
development of environmentally clean processes, mainly based on the 63.
use of compressed fluids, for food ingredients production and (25) Faeste, C. K.; Ronning, H. T.; Christians, U.; Granum, P. E. J.
advanced analytical techniques for food ingredients characterization. Food Prot. 2011, 74, 316−345.
She is the Secretary of the Spanish Society of Compressed Fluids (26) Raz, S. R.; Haasnoot, W. TrAC, Trends Anal. Chem. 2011, 30,
(Flucomp), the Vice-President of the Spanish Society of Chromatog- 1526−1537.
raphy and Related Techniques (SECyTA), and the delegate from (27) Atalay, Y. T.; Vermeir, S.; Witters, D.; Vergauwe, N.;
Spain in the Domain of Food and Agriculture in COST Actions. Verbruggen, B.; Verboven, P.; Nicolai, B. M.; Lammertyn, J. Trends
Alejandro Cifuentes is a Full Research Professor at the National Food Sci. Technol. 2011, 22, 386−404.
(28) Schrader, C.; John, R.; Scheilke, A. J. Food Saf. Food Qual. 2011,
Research Council of Spain (CSIC) in Madrid and head of the
62, 36−51.
Laboratory of Foodomics. His activity includes advanced analytical (29) Kantiani, L.; Llorca, M.; Sanchis, J.; Farre, M.; Barcelo, D. Anal.
methods development for foodomics, food quality and safety, food Bioanal. Chem. 2010, 398, 2413−2427.
bioactivity, as well as isolation and characterization of biologically (30) Magnuson, B. A.; Jonaitis, T. S.; Card, J. W. J. Food Sci. 2011, 76,
active natural products. He is Editor of TrAC and Electrophoresis and a R126−R133.
member of the Editorial Board of 12 international journals. (31) Armenta, S.; Garrigues, S.; de la Guardia, M. TrAC, Trends Anal.

■
Chem. 2008, 27, 497−511.
ACKNOWLEDGMENTS (32) Wittwer, J.; Rubio-Aliaga, I.; Hoeft, B.; Bendik, I.; Weber, P.;
Daniel, H. Mol. Nutr. Food Res. 2011, 55, 341−358.
M.H. would like to thank MEC for his Ramón y Cajal contract. (33) Williams, C. M.; Ordovas, J. M.; Lairon, D.; Hesketh, J.; Lietz,
This work was supported by Projects AGL2011-29857-C03-01 G.; Gibney, M.; van Ommen, B. Genes Nutr. 2008, 3, 41−49.
and CONSOLIDER INGENIO 2010 CSD2007-00063 FUN- (34) Smith, C. E.; Ordovas, J. M.; Sanchez-Moreno, C.; Lee, Y. C.;
C-FOOD (Ministerio de Educación y Ciencia). Garaulet, M. Int. J. Obesity 2012, 36, 130−136.

■ REFERENCES
(1) Hamburg, M. A. Science 2011, 331, 987.
(35) Corella, D.; Arnett, D. K.; Tucker, K. L.; Kabagambe, E. K.;
Tsai, M.; Parnell, L. D.; Lai, C. Q.; Lee, Y. C.; Warodomwichit, D.;
Hopkins, P. N.; Ordovas, J. M. J. Nutr. 2011, 141, 2219−2225.
(2) Cifuentes, A.; Dugo, P.; Fanali, S. J. Chromatogr., A 2011, 1218, (36) Kau, A. L.; Ahern, P. P.; Griffin, N. W.; Goodman, A. L.;
7385−7386. Gordong, J. I. Nature 2011, 474, 327−336.
(3) Señorans, F. J.; Ibañez, E.; Cifuentes, A. Crit. Rev. Food Sci. Nutr. (37) Soni, K. A.; Nannapaneni, R.; Tasara, T. Foodborne Pathog. Dis.
2003, 43, 507−526. 2011, 8, 843−852.
(4) Herrero, M.; Simó, C.; García-Cañas, V.; Ibáñez, E.; Cifuentes, A. (38) Mercenier, A.; Wiedermann, U.; Breiteneder, H. Curr. Opin.
Mass Spectrom. Rev. 2012, 31, 49−69. Biotechnol. 2001, 12, 510−515.
(5) Ibañez, E.; Cifuentes, A. Crit. Rev. Food Sci. 2001, 41, 413−450. (39) García-Cañas, V.; Simó, C.; León, C.; Ibáñez, E.; Cifuentes, A.
(6) Dufour, E. Int. J. Dairy Technol. 2011, 64, 153−165. Mass Spectrom. Rev. 2011, 30, 396−416.
(7) Herrero, M.; Ibáñez, E.; Cifuentes, A.; Bernal, J. J. Chromatogr., A (40) O’Flaherty, S.; Klaenhammer, T. R. Ann. Rev. Food Sci. Technol.
2009, 1216, 7110−7129. 2011, 2, 353−371.

10158 dx.doi.org/10.1021/ac301680q | Anal. Chem. 2012, 84, 10150−10159

Analytical Chemistry Feature

(41) Hertog, M. L.; Rudell, D. R.; Pedreschi, R.; Schaffer, R. J.;

Geeraerd, A. H.; Nicolai, B. M.; Ferguson, I. Postharvest Biol. Technol.
2011, 62, 223−237.
(42) Ibáñez, C.; Valdés, A.; García-Cañas, V.; Simó, C.; Celebier, M.;
Rocamora, L.; Gómez, A.; Herrero, M.; Castro, M.; Segura-Carretero,
A.; Ibáñez, E.; Ferragut, J. A.; Cifuentes, A. J. Chromatogr., A 2012,
1248, 139−153.
(43) Valdés, A.; Simó, C.; Ibáñez, C.; Rocamora, L.; Ferragut, J. A.;
García-Cañas, V.; Cifuentes, A. Electrophoresis 2012, 33, 2314−2327.
(44) Kaspar, S.; Peukert, M.; Svatos, A.; Matros, A.; Mock, H.
Proteomics 2011, 11, 1840−1850.
(45) Gehlenborg, N.; O’Donoghue, S. L.; Baliga, N. S. Nat. Methods
2010, 7, S56−S68.

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