Green Foodomics

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provided by Digital.CSIC Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2

Chapter 18:

Green Foodomics

Jose A. Mendiola, María Castro-Puyana, Miguel Herrero, Elena Ibáñez*

Institute of Food Science Research (CIAL, CSIC-UAM), Nicolás Cabrera 9, Campus

de Cantoblanco, 28049 Madrid, Spain.

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Abstract

The reader has enjoyed different aspects of Foodomics from different points of view in this book. Interestingly, every approach seen so far could be made greener. In the present chapter we will try to show how to make a Green discipline such as

Foodomics, even greener by applying basic concepts of Green Chemistry in all the areas covered by Foodomics: functional ingredients production and analytical methodologies development. Researchers of different areas are aware of the advantages offered by automation, miniaturization, and direct analysis. These approaches are important, not only to increase laboratory throughputs, but also to enhance safety (for environment and for humans) and sustainability. In this chapter, two case studies have been carried out in terms of Life Cycle Assesment (LCA), one focused on antioxidant extract production and other focused on advanced analytical methodologies.

Keywords:

Green Chemistry; Life Cycle assessment; Green Processes; Environmental impact;

Extraction techniques

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18.1. Basic concepts of Foodomics (and how to make it greener)

Foodomics has been defined as a new discipline that studies the food and nutrition domains through the application of advanced omics technologies in order to improve consumer‘s well-being, health, and confidence (Cifuentes, 2009; Herrero et al., 2010a,

2012). Undoubtedly, Foodomics tries to provide new answers to the new challenges that researchers and society face in this 21st century. Some of these challenges are to preserve sustainability as well as food quality and safety as a way to improve consumer‘s well-being and confidence. Another challenge is to contribute to the rational design and development of new foods, with new targets other than the nutrition, more focused on health improvement and disease prevention; and to be able to provide these answers with supported scientific evidences. These goals are basically ―green‖ by themselves since by reaching them it will be possible to have safer and healthier foods while decreasing contamination and chemical hazards.

Foodomics can help in this goal since most of the methodologies employed (and sub- disciplines involved) can be considered basically green: -omics technologies, bioinformatics, advanced analytical chemistry (for food quality and safety) and food production and design (through the development of functional foods and nutraceuticals), etc. In the present chapter we will try to show how to make a Green discipline such as Foodomics, even greener by applying basic concepts of Green chemistry in all the areas included in Foodomics (see Figure 18-1, in which concepts marked with a star mean that they can be greened). Therefore, we will discuss different green alternatives for functional food ingredients production (based on the use of green solvents and integrated processes producing less waste and less energy

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Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 consumption), ways to green analytical methods for food quality, safety and traceability measurements (through the use of miniaturized sample preparation techniques or greener solvents and the development of new alternatives for greener separation techniques) and, at the end, ways to influence -omics technologies (mainly proteomics and metabolomics) to reduce even further the preparation steps, the consumption of solvents while improving data reliability. By ―thinking green‖ it will be possible to reach Foodomics goals but with an additional benefit for our society.

18.2. Basic concepts on Green Chemistry

Developed societies are becoming increasingly concerned about the environment and how this is affected (and how will be affected in the future) by different chemical and engineering activities at both, industrial and laboratory scale. Since early 90‘s, the

Green Chemistry movement has been exploring ways to reduce the risks of chemical exposure to humans and environment. Simply stated, Green Chemistry reduces or eliminates the use or generation of hazardous substances from chemical products and processes and improves all types of chemical products and processes by reducing impacts on human health and environment. As defined by Anastas and Warner

(Anastas and Warner, 1998) ―Green Chemistry is the use of chemistry techniques and methodologies that reduce or eliminate the use or generation of feedstocks, products, by-products, solvents, reagents, etc. that are hazardous to human health or the environment‖. Green Chemistry technologies involve all types of chemical processes, including synthesis, catalysis, reactions, separations, analysis and monitoring. There

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Chemistry: waste, hazard (health, environmental and safety) and energy.

Green chemistry is not a simple subdivision of chemistry like organic or organometallic chemistry; it has environmental, technological and social goals and is linked to the wider sustainability movement (Winterton, 2001). Green chemistry has set itself the goal of making chemical technology more environmentally benign by

‗efficiently using (preferably renewable) raw materials, eliminating waste and avoiding the use of toxic and/or hazardous reagents and solvents in the manufacture and application of chemical products‘ (Sheldon, 2000).

18.2.1. Green Processes

As seen for Green Chemistry, Green Engineering is the ―development and commercialization of industrial processes that are economically feasible and reduce the risk to human health and environment‖. Both green concepts are intimately related to sustainability, which means using methods, systems and materials that will not deplete resources or harm natural cycles (Anastas et al., 2003).

An approach to quantitatively and systematically evaluate synthetic organic reactions and processes was described by Curzons et al. (2001). The results of their work indicated that close attention to effective use and reuse of solvents result in the largest gains for reducing life cycle impacts in batch chemical operations. The most common strategy is to perform Life Cycle Assessment (LCA). LCA is a standardized methodology, according to ISO 14044 (ISO 14044, 2006), for assessing the environmental impacts associated with a product, process or service, over its entire

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As mentioned, one of the goals of Foodomics is to provide with scientific evidences to demonstrate the real effects of newly developed functional foods; in this sense, there is a growing interest in the use and development of new Green processes to obtain such bioactives. Below, in section 18.3 of this chapter, new approaches will be considered towards the extraction of new bioactive components from different natural sources. These new processes contemplate both, the use of Green solvents and the decrease in energy requirements by improving the efficiency and shortening the time.

At the end of the section, new processes based on the use of compressed fluids

(subcritical water and supercritical CO2) will be discussed in terms of LCA for the production of a potent antioxidant extract from rosemary leaves with application in the development of new functional foods.

18.2.2. Green Analytical Chemistry

Keeping in mind LCA strategies, analytical methods can be considered as processes in which preliminary information and knowledge, solvents, reagents, samples, energy and instrument measurements are used as inputs to solve a specific problem. The outputs of those processes are qualitative and/or quantitative composition of the analytes. However, analytical methodologies can also have side effects (e.g., energy consumption, wastes that could create risks for operators and damage the environment, etc.). These side effects of methods, and waste generation and management are also the responsibility of method developers and users (Garrigues et

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Although the analytical community was environmentally sensitive and the idea of improving analytical methods by reducing consumption of solvents and reagents pre- dates the theoretical developments, the first descriptions of ―Green Analytical

Chemistry‖ methods (or clean analytical methods) appeared by mid-90‘s (Armenta et al., 2008), as can be seen in Figure 18-3, in which the evolution of the number of research papers dealing with ―Green Analytical Chemistry‖ is shown.

The key points, regarding adverse environmental impact of analytical methodologies, have been:

- sample pre-treatment: reduction of the amount of solvents required;

- amount and toxicity of solvents: reduce solvents and reagents employed in the

measurement step, especially by miniaturization;

- development of alternative direct analytical methodologies not requiring

solvents or reagents (Armenta et al., 2008).

In this sense, these three main areas should be considered when developing a new analytical method or improving an existing one. Moreover, other important aspects should be considered for a successful use of Green Analytical Chemistry, which was defined by L.H. Lawrence as: ―the use of analytical chemistry techniques and methodologies that reduce or eliminate solvents, reagents, preservatives and other chemicals that are hazardous to human health or the environment and that may also enable faster and more energy-efficient analysis without compromising performance criteria‖ (Sandra et al., 2010). In this definition it is clear that when dealing with

Green Analytical Chemistry two terms has to be considered. The hazard has to be

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In this sense, new approaches such as those concerning the greening of sample preparation with the use of new green solvents, miniaturization, or the employment of solvent-free techniques are of paramount importance and will be discussed in detail below in section 18.4. For a deeper and more general knowledge of green sample preparation techniques some other reviews are recommended (Curyło et al., 2007;

Pawliszyn et al., 2010; de la Guardia et al., 2011a).

The growth of -omics technologies is helping the other two key areas to develop clean analytical methods. The combination of modern analytical techniques with breakthroughs in microelectronics and miniaturization allows the development of powerful analytical devices for effective control of processes and pollution.

Combining miniaturization in analytical systems with advances in chemometrics is also of interest. The evolution of chemometrics has supported development of solvent-free methodologies based on mathematical treatment of signals obtained by direct measurements on untreated solid or liquid samples. The growth and evolution of chemometrics has shown that spectroscopic/spectrometric methods could be the best way towards Green Analytical Chemistry (Armenta et al., 2008).

18.3. Green processes to produce functional food ingredients

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The development of green processes for extracting functional ingredients from natural sources is one of the fields of interest in Foodomics. When searching for functional ingredients, an important aspect that has to be considered is how they are obtained.

Traditional extraction techniques (Soxhlet, sonication, Solid-Liquid Extraction (SLE),

Liquid-Liquid Extraction (LLE)) require long extraction times and large amounts of samples, provide low selectivity and, generally, low extraction yields, and need high volumes of organic solvents, resulting in the generation of large quantities of solvent waste that can cause environmental problems. Because of the use of hazardous solvents should be avoided from the Green and Sustainable point of view, selective and environmentally-friendly extraction procedures to isolate bioactive compounds from natural sources, combined with food-grade solvents are required.

In this regard, there is an enormous interest in the application of more environmental friendly techniques that can overcome the drawbacks of traditional extraction procedures. Among the Green extraction procedures, Ultrasounds Assisted Extraction

(UAE) and Microwave Assisted Extraction (MAE) are versatile approaches due to the possibility of using several solvents of different polarities, allowing fast extractions and decreasing the amount of solvents used. Whereas UAE is based on acoustic cavitation that cause disruption of cell walls, thus, reducing the particle size and increasing the contact between the solvent and the compounds, MAE uses microwave radiation to cause motion of polar molecules and rotation of dipoles to heat solvents, promoting transfer of target compounds from the matrix to the solvent. On the other hand, the development of advanced pressurized extraction techniques such as

Supercritical Fluid Extraction (SFE), Pressurized Liquid Extraction (PLE) or

Pressurized Hot Water Extraction (PHWE, also called subcritical water extraction

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(SWE)), which perfectly comply with the principles of Green Chemistry and Green

Engineering, could represent a key point in sustainable development. In that sense, it is a good point to be able to switch to greener solvents such as CO2, ethanol or water.

The possibility of modifying the physicochemical properties of solvents (density, diffusivity, viscosity, dielectric constant) changing the pressure and/or temperature of the extraction, that also modifies their selectivity and solvating power, give these pressurized techniques a high versatility. Besides, they also offer the possibility of eliminating additional post-extraction procedures (centrifugation and filtration) since they retain the sample inside the extraction cell (Rostagno et al., 2010). The typical system used to perform SFE, PLE or PHWE basically consist on a solvent supply and a pump for pumping it, a heater for heating the solvent, a pressure vessel where the extraction is carried out, a pressure controller, and a device for collecting the extract

(see Figure 18-4).

To gain a deeper knowledge on the design of pressurized fluid extractors, the readers are referred to (Pronyk et al., 2009; Pereira et al., 2010; Teo et al., 2010; Turner et al.,

2011; Mustafa et al., 2011).

SFE is based on the use of solvents at temperatures and pressures above their critical points. CO2 is the solvent of choice to extract functional ingredients from natural sources by SFE since although other solvents (such as propane, butane or dimethyl ether) have also been proposed, none of them fulfill the principles of Green chemistry as CO2, which is inexpensive, environmentally friendly, is considered GRAS

(Generally Recognized As Safe) for its use in the food industry and its critical conditions are easily attainable. In addition, it can be easily removed after extraction by reducing the pressure. Considering the low polarity of supercritical CO2, SFE will

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Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 be more suitable for the extraction of compounds with low polarity. However, a change in its polarity can be obtained combining CO2 with co-solvents (polar modifiers such as ethanol or methanol) that increase its solvating power making supercritical CO2 able to extract more polar analytes. SFE has for long been used as technique to extract bioactive compounds (mainly antioxidants) from different species, such as plants, food-by-products or algae (Herrero et al., 2006; Herrero et al.,

2010b). Just to name some examples, phenolic compounds have been extracted from rosemary (Herrero et al., 2010c; Carvalho et al., 2005) pomegranate seeds (Liu et al.,

2009), or rice wine lees (Wu et al., 2009); carotenoids from tomato pomace (Shi et al.,

2009), carrots (Sun et al., 2006) or algae (Mendiola et al., 2005); and omega-3 from hake by-products (Rubio-Rodríguez et al., 2008).

PLE is broadly recognized as a Green extraction approach, mainly due to its low organic solvent consumption. In this extraction procedure, the pressure is applied to allow the use of liquids at temperatures higher than their normal boiling point. The combined use of high pressures and temperatures provides faster extractions. Besides, high temperature can increase the analyte solubility and decrease the viscosity and the surface tension of the solvents, helping to reach more easily areas of the matrices improving the extraction rate (Mustafa et al., 2011). PLE is more flexible than SFE in terms of bioactive compounds that can be extracted since it is more versatile in terms of extraction solvents that can be used, which are selected depending on the polarity of the target compounds. However, it is less selective than SFE and therefore it would be possible to find interferences in the extract. A high number of applications of PLE for obtaining bioactive compounds from different sources can be found in the literature. For a deeper knowledge of different applications of PLE, some interesting

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Mustafa et al., 2011; Wijngaard et al., 2012; Sun et al., 2012).

PHWE is a Green process that uses water as extracting solvent at high temperature

(above its atmospheric boiling point (100 ºC) and below its critical temperature (374

ºC)) and at pressure high enough to keep the water at liquid state. Therefore, it can be considered a particular application of PLE with water as extracting agent. Physical and chemical properties of water change dramatically under high temperature. For instance, its dielectric constant decreases from around 80 at 25 °C to around 33 at 200

ºC (that is, close to a polar organic solvent such as methanol), viscosity and surface tension are both reduced while diffusivity increased; under these conditions, the extraction process is enhanced in terms of efficiency and speed. Besides, the solubility of different bioactive compounds is also modified by temperature, favoring their transfer from the matrix to the heated liquid water. In terms of Green Chemistry and

Green Engineering, water is the greenest solvent that can used since it has negligible environmental effect, non-toxicity to health and the environment and it is safe to work with and to transport. The reader is referred to different reviews (Herrero et al., 2006;

Mendiola et al., 2007; Wiboonsirikul et al., 2008; Teo et al., 2010; Wijngaard et al.,

2012) and a book chapter (Turner et al., 2011) already published to gain a deeper knowledge on the extraction of bioactive compounds from different sources by

PHWE.

An interesting comparison of the environmental impacts associated to the above- mentioned pressurized extraction procedures (namely, SFE and PHWE) and a traditional extraction technique (Soxhlet with hexane as extracting solvent) for the production of 1 g of antioxidant extract from rosemary leaves is presented in terms of

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LCA (using the software SimaPro 7.33 (Prè consultants, Netherland)). To be able to compare the three techniques, the optimum conditions for providing dry rosemary extracts with high antioxidant activity have been considered (Herrero et al., 2010c;

Lagouri et al., 2010). Figure 18-5 shows the diagram of the 3 extraction processes considered to obtain antioxidants from rosemary leaves, including system boundaries and optimum extraction conditions. Table 18-1 shows the key inventory data for production of dry rosemary extracts (1 g) by the three processes. The steps previous to the extraction and those after production stage are not included for simplification

(they are assumed to be identical for all the processes studied) and the energy consumption of each component employed in the extraction process was calculated based on their specification (for commercial equipment) and uptime. The characterization method used was CML 2 baseline 2000 V2.05. Along with the impact categories included in this method, the cost derived by the energy employed in each process was added considering the energy price for industrial consumers published by the Europe´s Energy Portal (€ per kWh for a consumption of 1

GWh/year) (Europe´s Energy Portal. http://www.energy.eu/#Industrial-Elec –checked on May 2012–). Figure 18-6 shows the environmental impacts in the different categories considered by the LCA approach for the three extraction processes considered (bars have been normalized considering Soxhlet extraction as 100%). An analysis of the possible factors affecting all the environmental impact categories demonstrates the high significance of electricity consumption of the three processes.

Besides, it is clear that extraction solvents used in PHWE and SFE have no important impact (they are green solvents and are used in low volumes) whereas the impact of

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Table 18-1. Key inventory data for production of rosemary extracts (1 g) by PHWE, SFE and soxhlet extraction with hexanea. PHWE SFE Soxhlet Products Rosemary extract 1 g 1 g 1 g Inputs From nature Rosemary 2.6 g 15.4 g 23.3 From technosphere Water 47.5 g - Nitrogen 0.12 kg - Hexane - - 230.2 g Carbon dioxide - 27.7* g - Ethanol - 1.9* g - Electricity 10.7 kWh 3.9 kWh 12.2 kWh Outputs Emissions to air Water - - - Nitrogen - - - Carbon dioxide - 27.7* kg Waste to treatment Solid waste 1.6 g 14.4 g Waste water 47.5 g - Solvents mixture - 1.9* g residue - - 22.3 Hazardous waste - - 230.2 g

a Data to perform LCA has been taken from three different databases Ecoinvent 2.0, ELCD and LCA food DK.

*The amounts of CO2 and ethanol corresponded with the net value used taking into account a recycling of 95 % and a loss of 5 % from

the initial amounts (0.5 kg and 38.8 g of CO2 and ethanol respectively)

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As a step to the future, the idea of multiple integrated processes arrives with enormous potential; these processes involve the development of multiunit operations with the possibility of using different fluids. This approach can provide advantages in the development of a Green processing platform able to face some of the challenges in our society such as environmental impact, sustainability, energy preservation and health (King et al., 2009; Turner et al., 2011; Ibáñez et al., E, 2012a). This Green

Platform should work with environmentally benign solvents such as liquefied or supercritical CO2, for non-polar to moderately polar solutes, and with pressurized hot water (between its boiling and critical points) for a wider range of polarities, considering also the use of ethanol as co-solvent together with water or carbon dioxide.

Several examples can be found in the literature about integrated processes that may favor the extraction and purification of bioactives. Among them, some deal with

Green processes to extract bioactive compounds (Liau et al., 2010) and others can be used as a base for converting the reported processes to more Green, sustainable and efficient ones (Athukorala et al., 2006; Moreda-Piñeiro et al., 2007; Siriwardhana et al., 2008). Processes related to enzymatic hydrolysis and extraction can be easily included in the Green Platform. Some studies have demonstrated that under pressurized conditions, enzymatic hydrolysis is accelerated; this fact gives a stronger support to the possibility of improving processes through the use of integrated pressurized fluid technologies (Moreda-Piñeiro et al., 2007). For instance, Turner´s research group demonstrated the viability of a process combining enzymatic hydrolysis in hot water, using a thermostable β-glucosidase to catalyze hydrolysis of

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This process was preferred over more conventional extraction/hydrolysis processes regarding primary energy consumption and global warming potential (Turner et al.,

2006; Lindahl et al., 2010).

It should be borne in mind that the extraction of bioactive compounds is an important step to develop a Foodomics platform able to improve our understanding on how these compounds interact at molecular and cellular level. Green pressurized technologies above mentioned, has been used in several works. In this sense, this knowhow is used as extraction method (sample preparation) in analytical platforms that allowed carrying out proteomics, metabolomics or transcriptomics studies to evaluate the health benefits of functional food ingredients (Ong et al., 2004; Leon et al., 2009; Ruperez et al., 2009; Ibáñez et al., 2012b).

18.4. Development of Green Analytical processes for Foodomics

As mentioned throughout the book, the use of -omics techniques such as transcriptomics, proteomics and metabolomics in Foodomics derives from the search of massive information at different expression levels (transcriptome, proteome, metabolome) able to provide a better understanding of the molecular effects of, for instance, a functional food in certain organism, or to asses, for instance food quality, authenticity and safety.

Undoubtedly, each analytical process will include several steps and is impossible to approach each of them individually. In this section, some strategies applied to general steps will be discussed in terms of how to improve them from a Green point of view.

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The main idea behind consists of providing the reader with some of the new advances and tools to make Foodomics discipline greener; the use of some of them in a particular analytical process will depend on the application itself and on the goal established. By no means can be considered an exhaustive evaluation of all the processes involved in such complex discipline. The analytical chemist will have to take decisions of how or when to implement them, without sacrificing the main purpose of the analytical determination.

Therefore, ideas about how to green the sample preparation step and how to improve analytical methodologies under the umbrella of Green Analytical Chemistry will be presented, together with sound applications in the proteomics and metabolomics fields.

18.4.1. Direct analysis of samples. The Greenest approach

Undoubtedly, the clearest way to reduce wastes, energy, consumption of solvents and reagents is through the direct analysis of the samples. This approach is not always possible since most of samples need to be in solution or analytes of interest need to be selectively extracted and therefore, no direct determination can be done.

Methodologies mostly employed in Foodomics related to direct analysis involve the use of MS-based procedures (like DART (Direct Analysis in Real Time)-MS, PTR

(Proton Transfer Reaction)-MS, IM (Ion Mobility)-MS, among others) and NMR

(Nuclear Magnetic Resonance). However, other techniques, as e.g., spectroscopic techniques (such as NIR (Near Infrared) and Raman spectroscopy) can provide also interesting information to Foodomics evaluations.

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Among spectroscopic techniques, NIR gives chemical and physical information about samples employing data related to molecular vibrations detected in the infrared region near the range of visible light frequency under the wavelength of 2500 nm. It is nondestructive, needs no sample preparation and allows analysis in very short time.

The main drawbacks are related to the high limit of detection and the complexity of the spectra. The development of the technique, together with chemometric tools, has allowed, for example, the measurement of green tea quality as affected for different manufacturing processes and green tea varieties (Ikeda et al., 2007). Recent works have also developed new software that allowed its use for metabolic fingerprinting of food (Ikeda et al., 2009).

On the other hand, Raman spectroscopy (which considers the scattered radiation of frequencies different from that provided in the incident monochromatic radiation) has been used to obtain molecular fingerprints of the samples under study. This technique has been employed, for instance, for in-vivo lipidomics, to profile the oil produced by a microalgae cell in a direct, quantitative and fast way (Wu et al., 2011). The possibility of using Raman spectroscopy, together with NMR and MS-based methods for metabolic fingerprinting in disease diagnostics has been reviewed (Ellis et al.,

2007).

Among the different techniques that can be used for a direct analysis of the samples,

NMR and MS-based methods are the most employed in metabolomics and food applications. In fact, more than 1300 records can be found in the literature dealing with NMR and metabolomics (Sciverse-Scopus database, 2012 Elsevier B.V). NMR is based on the different resonance frequencies exhibited by nuclei (mainly hydrogen and carbon atoms) positioned into a strong magnetic field. NMR has been used, for

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2012) and to predict the sensorial quality of canned tomatoes by means of metabolomics fingerprints correlated to sensory descriptors such as bitterness, sweetness, sourness and saltiness (Malmendal et al., 2011). Moreover, NMR together with chemometrics has been employed for identifying urinary metabolite profiles able to discriminate the dietary intake of protein during a dietary intervention (Rasmussen et al., 2012) and has been also suggested as one of the methods for gathering scientific evidence from clinical trials in dietary intervention studies, in a Foodomics approach

(Puiggròs et al., 2011).

MS-based methods are probably the most used for metabolite profiling/fingerprinting.

Frequently, samples are subjected to an extensive preparation previous to their introduction into the MS system or into the separation system coupled on-line to MS.

Recently, a new sample ionization source, called DART, has been developed allowing a direct and rapid identification of analytes in different types of samples (including solid samples), without any sample treatment (Cody et al., 2005). DART coupled to different types of MS analyzers has been used for measuring food authenticity, quality and safety; Hajslova et al., have discussed different applications of DART in complex food matrices (Hajslova et al., 2011), including optimization of the operating conditions, and the use of DART for pesticides, detection of adulteration by melamine, mycotoxins, migration of packaging materials into the food products, food authentication, etc. For instance, DART-TOFMS has been employed for metabolomics fingerprinting/profiling of beer origin in real time (Cajka, et al., 2011).

On the other hand, PTR-MS has been suggested as a potent high throughput technique for metabolomics, targeting volatile analysis without a previous sample preparation

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(Cappellin et al., 2012) and for fingerprinting of food samples in processes relevant to the food industry such as coffee roasting, acrylamide production during Maillard reaction, metabolic and catabolic reactions of fruits and meat during storage and in vivo monitoring of flavor release during consumption, directly related to food perception; a review has been recently published by Biasioli et al., (Biasioli et al.,

2011).

The last MS-based technique that will be presented in this section is ion-mobility spectrometry (IMS) that allows the direct introduction of solid and liquid samples into the MS analyzer by thermal desorption in which the vapor generated is ionized by atmospheric pressure chemical ionization (APCI) to produce ions. This approach has been used, for example, for metabolic profiling of human blood (Dwivedi et al.,

2010); the methodology allowed the detection of around 1100 metabolite ions among which amino acids, organic acids, fatty acids, carbohydrates, purines, etc. were observed.

Thus, it is clear that there are many options to work avoiding sample preparation and therefore, meeting the requirements of Green Analytical Chemistry in terms of minimizing the use of solvents and, thus, reducing wastes and operator risks.

Nevertheless, the above mentioned techniques (and others that have not been included) are not always available. Moreover, samples are usually too complex to use direct analysis since the compounds of interest might not be present in the sample at the minimum levels to perform their detection and quantification directly, without any previous extraction and pre-concentration step. In those cases, sample preparation

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18.4.2. Green sample preparation techniques

As previously seen, analytical methods constitutes itself a potential risk by reiteration of operations that need solvents, chemicals, energy and yield wastes. ―Green

Analytical Chemistry‖ principles can be implemented at each stage of the analytical process. Sample preparation, is typically considered one of the ―bottlenecks‖ of any analytical procedure, not only in throughput but also in terms of greening the analysis.

Sample preparation operations are characterized by their complexity, diversity, tediousness and diﬃculty of automation. The desire to spend less time, effort, and resources on sample preparation has created a trend for more selective sample preparation procedures that achieve better clean-up and improved analysis at lower concentrations. It also important to keep in mind that the best clean-up treatment is no-treatment, but, as previously seen, this statement is not possible most of the times.

Sample preparation procedures considering greenness issues are not always easy to develop. In fact, a closer look at the scientific literature shows that sample treatment has been the most evaluated analytical step in terms of greenness. The advancement of sample preparation tools chases the following goals (de la Guardia et al., 2011a):

a. reduce amount of sample to treat

b. reduction or elimination of pollutant solvents/acids (miniaturization)

c. multiple compound extraction simultaneously

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d. increase automation and throughput determination.

The advent of advanced MS technologies in recent years had several consequences on our analytical work including the sample preparation step. The higher sensitivity and selectivity of modern mass spectrometers combined with LC and/or GC, make possible to simplify and miniaturize sample preparation. There is no big need for enrichment in the sample preparation step, which in the past was of vital importance, because samples needed to undergo a chain of specific treatments to make them compatible with the sensitivity of the analytical techniques used (Sandra et al., 2011).

There are several reviews and publications dealing with Green Sample Preparation techniques for environmental analysis (Tobiszewski et al., 2009; Curyło,et al., 2007) and for food analysis (Sandra et al., 2008); but not many works has been published to date applied to -omics.

When dealing with metabolomics and/or Foodomics, some of the analytes are non- volatile or semi-volatile and the matrixes include solid and liquid samples. The first step is, normally, a solvent extraction step to enrich the target solutes from the matrix.

Soxhlet extraction was introduced in 1850 and requires large amounts of solvent, energy and time. As previously seen, more environmentally friendly techniques such as UAE, SFE, PLE, PHWE, MAE and matrix solid-phase dispersion (MSPD, or its variant QuEChERS), are being used (Sandra et al., 2011). All of these techniques have in common the drastic reduction in the amount of solvents used since other physical processes such as pressure, temperature, microwaves, high frequency acoustic waves, among others, are applied to improve the efficiency and to speed up the extraction process, as compared to the conventional ones. These new methods

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When dealing with volatile analytes, solvent-free techniques can be used. Gas phase sampling is intensively used in food analysis and recently in metabolomics (breath analysis) (Guamán et al., 2012; Kim et al., 2012a). The main used volatile analysis techniques are headspace sampling static (SHS) or dynamic (DHS), in-tube extraction

(ITEX), purge and trap (P&T), gas phase stripping, solid phase microextraction

(SPME), and headspace sorptive extraction (HSSE).

For example, among the different procedures that can be used in comprehensive omics-based analyses providing insights into complex metabolic networks of biological systems, MALDI-imaging mass spectrometry (MALDI-IMS) has been recently employed to visualize the spatial distribution of biomolecules without extraction, purification, separation, or labeling of biological samples (Goto-Inoue et al., 2011). This advanced technique could use several sample preparation procedures, among them, the greener are cryomicrotome and freeze-fracture techniques, but sublimation has recently appeared as a fast and solvent-free technique to be used as sample preparation for MALDI-IMS omics analysis (Hankin et al., 2007).

In other cases it becomes necessary to derivatize samples, which usually increases the environmental impact of analysis, because reagents and solvents are required. For

Green Foodomics, the ideal situation is to eliminate the need for derivatization.

However, if derivatization is still required for analysis, the use of less hazardous chemicals is a step toward a greener methodology (Keith et al., 2007). For instance,

Fabbri et al., (Fabbri et al., 2005) developed a method for derivatization of fatty acids greener than the traditional methylation method using BF3-methanol. Their method

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Another advantage of the above mentioned processes is the possibility of automation, thus increasing the speed of sample measurement processes, and miniaturization, thus further reducing the amount of reagents used. Overall, these processes, including the simultaneous treatment of samples and the multianalyte determination in a single run help achieving greener processes and contribute to the sustainability of the method.

It must be clear that these approaches should only be undertaken when analytical features are not compromised in terms of selectivity, accuracy, representativeness and sensitivity. If the new green method does not meet the quality criteria needed, it should not be considered an alternative.

18.4.3. Green separation techniques

Among the most used separation techniques employed in Foodomics, chromatographic and electrophoretic techniques are excellent platforms for the separation, profiling, and quantification of target compounds in complex samples. In this section, the different approaches used to make separation techniques (including gas chromatography, GC; liquid chromatography, LC; supercritical fluid chromatography, SFC; capillary electrophoresis, CE and microanalytical systems) greener for metabolomics and proteomics will be addressed. For simplification, all techniques will be considered on-line and off-line with MS for the separation,

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18.4.3.1. Gas Chromatography and Supercritical Fluid Chromatography

Gas chromatography is undoubtedly the technique of choice when dealing with volatile and semi-volatile analytes. GC is inherently a Green separation technique compared to LC since it does not make use of toxic organic solvents as mobile phase and therefore, no wastes and no toxic hazard for the operators is expected. Moreover,

GC can be even greener if solvent-free sample preparation techniques are implemented as previously mentioned.

On the other hand, one of the main drawbacks of GC is its inability for analyzing certain compounds without derivatization (highly polar or non-volatile) and the high temperatures used for analytes elution, which requires high energy consumption.

Therefore, what seems clear is that GC should be selected from a Green point of view for certain applications but not always since for some metabolomics studies, in which polar compounds are involved, the selection of LC can be more convenient to meet the performance criteria and also from a green approach.

One of the ways to contribute to ―Green Analytical Chemistry‖ is through the reduction on analysis time while maintaining separation and resolution. To be able to do so, shorter columns with smaller internal diameters are suggested to provide with similar column efficiencies and plate number. This way it will be possible to reduce energy consumption and GC operating costs since the time per analysis will be also

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Another approach to reduce energy consumption has been the use of low thermal mass (LTM) technology that can be used for ultra-fast GC. This mode of chromatography should be only employed when resolution is not compromised

(Luong et al., 2006).

Supercritical Fluid Chromatography (SFC) was introduced in the later 80‘s as an alternative to normal-phase LC (NP-LC); main advantages over NP-LC are the increased diffusivity and resolution, the reduced viscosity, that allowed faster separations, and the lower solvent consumption, since only carbon dioxide plus small amounts (up to 20%) of polar solvents and/or additives are used during the analysis.

Therefore, to use SFC is always greener than employing LC, mainly considering the toxic organic solvents employed in NP-LC. Another advantage of SFC is the possibility of scaling up the separation processes to semi- or preparative scale, with an important reduction of the amount of solvents used. Due to its non-polar character,

SFC has been mainly used for metabolomics purposes to analyze lipid profiles in different types of complex samples, such as soybeans (Lee et al., 2012).

Phospholipids, glycolipids, neutral lipids or sphingolipids have been also analyzed by

SFC (Bamba et al., 2008).

However, undoubtedly, the most important field of application of SFC has been chiral separations for drug discovery, with about 260 references found in June, 2012 in

Sciverse-Scopus database dealing with SFC and chiral analysis. Some of these new approaches have been also suggested for the separation of urinary metabolites isomers by SFC with chiral stationary phases (Wang et al., 2006).

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18.4.3.2. Liquid Chromatography

A search of the scientific literature shows that LC is the separation technique most extensively used for metabolomics; in June, 2012, more than 500 references were found in Sciverse-Scopus database using the keywords ―LC-MS and metabolom*‖

(using * as a wildcard in the search query). HPLC is an efficient separation technique that can be used to appropriately separate different groups of compounds, of different chemical classes such as hydrophilic, hydrophobic, salts, acids, bases, etc. HPLC, opposite to GC, is not limited to the separation of thermally stable volatile or semi- volatile compounds; its separation mode depending on the chemical nature of the target solute(s). These modes include RP (reversed-phase), NP (normal phase), ion exchange, chiral, size exclusion, hydrophilic interaction liquid chromatography

(HILIC), and mixed modes. The properties in terms of mobile and stationary phases and separation mechanism will depend on the metabolites of interest, its concentration in the sample and the presence of interfering compounds.

In terms of ―Green Analytical Chemistry‖, several approaches have been used to develop Green strategies applied to LC. In Figure 18-7, the different strategies are shown, and can be divided in:

i) replacement of toxic organic solvents;

ii) minimizing use of solvents through the use of monolithic and nonporous

stationary phases and

iii) minimizing use of solvents through the miniaturization of the technique

(UPLC, nano-LC).

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At present, most of the mobile phases used in RP-HPLC consist on binary mixtures acetonitrile/water or methanol/water. Both, methanol and acetonitrile have favorable properties for LC use such as compatibility with water, low UV absorbance (in a wide

λ range), relatively low viscosity, high purity and low reactivity. Nevertheless, from an environmental point of view, they offer several drawbacks such as high toxicity and high disposal costs. Although it is true that methanol is considered less toxic than acetonitrile for analytical applications, methanol cannot be always used instead of acetonitrile mainly its different selectivity. Undoubtedly, selection of other solvents such as water, ethanol or even acetone can make the chromatographic process greener, mainly when selectivity can be optimized through a correct method development for separation of highly complex samples.

A new approach based on HILIC for the separation of polar and ionizable compounds in metabolomics was introduced in 2002 by Fiehn‘s group (Tolstikov et al., 2002) and compared to NP-LC. The possibility of substituting the toxic organic compounds commonly employed in NP-LC by other less toxic solvents is also an advantage of the

HILIC technique. Recently, the use of ethanol mixed with CO2 in HILIC (dos Santos

Pereira et al., 2010) in an enhanced fluidity mode (water/ethanol/CO2) was confirmed for the separation of nucleobases with the same performance than using water/acetonitrile, thus demonstrating the viability of certain greener alternatives such as enhanced fluidity to the use of organic solvents.

A different way to replace toxic organic solvents is the employment of elevated temperatures in LC separations. Advantages associated are reduction in analysis time and in the amount of organic modifier in the mobile phase. Increasing water

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Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 temperature results in a reduced viscosity and an important decrease on the dielectric constant (and thus, on the polarity of the water), meaning that water starts dissolving less polar compounds as temperature increases. Therefore, in an ideal situation, we should be able to use only pure water for polar and non-polar metabolites elution only via a temperature programming (thermal gradient) during the analysis. For a comprehensive review on the topic, readers are referred to (Greibrokk & Andersen

2003). Although the theory is clear, there are only few pioneer works demonstrating the possibility of using high temperature-LC for metabolomics such as the one of

Gika et al., in which the application of high temperature LC for the global metabolite profiling of the plasma and urine of normal and Zucker (fa/fa) obese rats (Gika et al.,

2008) is presented.

ii) Minimizing use of solvents through the use of monolithic and nonporous stationary phases

Monolithic columns have been recently suggested for LC separations and involve the use of columns specially designed for independent control of pore size (meso- and macropore) in order to improve separation in terms of mass transfer kinetics, short analysis time, due to high permeability, and low backpressures. The use of monolithic columns provides an important reduction in terms of solvent consumption since faster separations (by a factor of 4) are obtained as compared to conventional LC columns.

Although an interesting application has been suggested for this type of columns in plant metabolomics (Tolstikov et al., 2003), its main use is in the field of proteomics, in which more than 170 documents have been found concerning the use of such columns for human proteome analysis (Van de Meent et al., 2011; El Deeb 2011;

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Iwasaki et al., 2012). Important developments are being carried out in this field in terms of evaluation and design of new materials for monolithic columns production

(Alzahrani et al., 2011, Calleri et al., 2012).

Partially porous stationary phases, formed by particles with a solid core and a relatively narrow layer of porous material, have several advantages over conventional completely porous stationary phases in terms of ―Green Analytical Chemistry‖. Since this type of columns have a shorter diffusion path (since the main part of the particle is non-porous and thus the compound cannot penetrate in it), faster analysis are expected with conventional LC systems, perfect for high throughput analysis. This approach has been used for the profiling of lipids in human and mouse plasma (Hu et al., 2008) and for comprehensive proteomics (François et al., 2009).

iii) Minimizing use of solvents through the miniaturization of the technique (UPLC, nano-LC)

A general alternative that can be always used to minimize reagents and wastes (and therefore, disposal costs) is the miniaturization of the techniques. LC has been one of the most studied techniques for using smaller dimensions, mainly due to the advantages associated such as: 1) better resolving power in shorter time; 2) less sample volume necessary for the analysis and 3) reduction of costs and toxicity of solvents (de la Guardia et al., 2011b).

One of the strategies for LC miniaturization is the reduction of either internal diameter of the column or particle size. The use of smaller internal diameters, together with shorter columns and smaller particles is one of the best ways to reduce solvents consumption. When using such microscale columns, one way to reduce solvent

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2 decreased by a factor (F) = (i.d. of conventional/i.d. downscaled) to work at uopt.

Using this theory, it can be seen that when switching from 4.6 mm columns to 2.1 mm columns, F equals 4.8 and flow rate might be decreased from 1 mL/min to 0.2 mL/min, without the separation being compromised. An additional gain in sensitivity is obtained under these conditions since less dilution of the solutes in the mobile phase occurs. Moreover, the required sample volume is also reduced, which is important in -omics applications dealing with biological samples. On the other hand, the use of microscale columns is now general in most laboratories and does not impose a challenge in terms of LC instrumentation as only requires minimizing extra- column volumes in the system to maintain the separation efficiency and performance.

Another option to decrease solvent consumption is by decreasing the column particle diameter in combination with column length; this way, we can keep the column efficiency and decrease analysis time obtaining faster separations with lower solvent consumption. Moreover, since efficiency versus mobile phase velocities curves are more flat with this type of columns, it is possible to increase the flow rate even further and therefore to obtain faster separations with the same efficiency. As a consequence, the use of particle diameters lower than 2 µm generates higher back-pressures along the column, which means that appropriate instruments able to operate at very high pressures are needed. The use of UHPLC (Ultra High Pressure LC) is also common now in most of the laboratories, mainly related to -omics applications.

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A further reduction on solvent consumption can be achieved by working with capillary or nano-columns in LC; in those cases, flow rates decreased substantially to

10-2500 nL min-1 for nano-LC. It is important to emphasize that in those cases, specific pumps able to provide with micro or nanoliter flows should be used and that working with high volume pumps operated in split-flow mode is not green and should be avoided. Capillary and nano-LC are typically used in proteomics (with more than

400 results in Sciverse-Scopus database dealing with ―nano LC and proteome*‖)

(Rosenling et al., 2011; Faurobert et al., 2009) and metabolomics (Myint et al., 2009) since together with higher efficiencies, a high sensitivity is achieved for small samples sizes due to the concentration-sensitive nature of nanospray-ESI-MS.

Applications to proteomics are related to the use of nano-LC-MS/MS for identifying protein spots detected by 2-DE (Huerta-Ocampo et al., J2012) or to study the embryo development in rice through proteomic analysis (Xu et al., 2012a) or studies related with biomarkers discovery in cancer (Yu et al., 2011; Roberts et al., 2012). The technique has been also used for peptidomics (Ueda et al., 2011) and metabolomics, for example, for identifying metabolites from in vitro and in vivo samples (Liu et al.,

2012), among many other studies.

18.4.3.3. Capillary electrophoresis

In terms of Green Analytical Chemistry, CE allows the replacement of established methodologies with greener methods that consume lower amount of solvents. CE, using an aqueous buffer to separate charged analytes, is really appealing as replacement of LC in some cases, since it provides with very high efficiencies, short analysis times, low sample and electrolyte consumption, easiness of operation and 18-33

Green Analytical Chemistry requirements.

CE has been widely used in -omics technologies (more than 280 articles in Sciverse-

Scopus database under ―capillary electroph*‖ and ―metabolom*‖). Relevant applications can be found on disease‘s biomarkers discovery (Kumar et al., 2012; Ban et al., 2012; Fuchs et al., 2011; Issaq et al., 2011), to study food treatments and its effects on the metabolome (Sugimoto et al., 2012), for non-targeted profiling analyses of herbal medicine extracts (Iino et al., 2012), or to the metabolic assessment of the nutraceutical effect of different natural extracts in animal models (Balderas et al.,

2010; Moraes et al., 2011, Godzien et al., 2011), etc.

But, it is mainly in the field of proteomics in which CE is more active. For instance, in a very recent review, Xu et al., (Xu et al., 2012b) discussed the advantages of different platforms for proteomics, based on the use of 2D CE, CE coupling with capillary LC, and microfluidic devices. Advantages mentioned are faster analysis, higher separation efficiency and less sample and solvent consumption than conventional methods based on LC or slab gel electrophoresis. Moreover, advantages of CE-MS as compared to LC-MS have been observed in the field of proteomics and peptidomics (Mullen et al., 2012). In general, an extensive number of references

(more than 900 considering capillary ―electroph* and proteom*‖) were obtained, although most of them showed the employment of CE in microfluidic systems, as will be mentioned in the following section.

18.4.3.4. Analytical microsystems (microfluidic, lab-on-a-chip, µTAS)

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Micro total analysis system (µTAS), known also as ―Lab-on-a-chip‖, attempts to develop integrated analytical systems at micro scale to perform in one device all analytical steps (sample preparation, analytes separation and detection) needed to carry out a complete analysis (Burns et al., 1998; Manz et al., 1990; Rios et al., 2006).

Challenges and difficulties in developing µTAS systems have been reviewed by Rios et al., (Rios et al., 2006), being its main benefits the analytical improvements associated with the scaling down of the size of the device, the minimized consumption of reagents and solvents, the increased automation, the reduced manufacturing costs and the use of an integrated platform that may allow the improvement, in terms of

Green Analytical Chemistry, of the different steps associated to a whole analysis

(Kock et al., 2000).

Microfluidic devices such as nano-LC/MS, CE-MS, etc. have been widely applied in proteomics and metabolomics. Nano-LC systems have demonstrated its ability in different fields such as the determination of certain abuse drugs and metabolites in human hair (Zhu, et al., 2012) or for biomarkers discovery (Houbart et al., 2011, Bai et al., 2011, Armenta et al., 2009; Horvatovich et al., 2007), among others. On the other hand, capillary electrophoresis has been widely applied to lab-on-a-chip systems. Using these types of chips it is possible to obtain high separation efficiencies in a very short time; as mentioned in the review by Rios et al., (Rios et al., 2006), there are several key reasons for the dominance of CE microchips over chromatographic techniques such as those related to CE analytical performance (like rapid analysis, high sample throughput, small volumes of samples, separation efficiency remaining or increasing while decreasing scale) and those intrinsic of miniaturization and technological developments (such as the easy fabrication of

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Some interesting applications of the mentioned microdevices are its use in single-cell analysis (Kim et al., 2012b). A very recent review by Yin et al., discusses the latest developments in microfluidics aimed at total single cell analysis on chip, from an individual live cell to its gene and proteins (Yin et al., 2012) and on the profiling of metabolites and peptides in single cells (Rubakhin et al., 2011).

Microchips have been also used as programmable diagnostic devices able to measure

DNA, proteins and small molecules in the same system (Jokerst et al., 2010), that can be used as disease diagnosis and prognosis for cancer, heart disease, etc.

18.5. Comparative LCA study of Green Analytical techniques. Case study

Throughout this chapter, several ways to make cleaner analysis and their implications have been described. In the present section of the chapter we will show some examples of quantification of the Green Profile of some analytical techniques used in

Foodomics. For this purpose LCA methodologies will be used. In fact, Gaber et al

(Gaber et al., 2011) suggested that the greenness should be incorporated during analytical method development, along with the conventional standards of accuracy, robustness, selectivity and reproducibility.

The American Chemical Society Green Chemistry Institute has introduced the

Greenness profile of the analytical methods that can be found in their website devoted

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PBT (persistent, bioaccumulative, and toxic), hazardous, corrosive and waste amount

(Keith et al., 2007), as shown in Figure 18-9. Probably, additional indicators should be included; these should be able to differentiate Green methods using aspects concerning energy and reagents consumed, and volumes of waste generated, and therefore other methodology should be used.

For profiling purposes, six advanced analytical methods used for characterization of rosemary antioxidant extracts developed in our laboratory have been selected namely:

HPLC-DAD and MECK-DAD (Ibañez et al., 2000) UHPLC-DAD-MS (Herrero et al.,

2010c), CE-MS (Herrero et al., 2005), SFC-FID (Ramírez et al., 2004) and GC-FID

(Ramírez et al., 2007). In all of them only the analytical part has been considered for

LCA purposes, excluding sample preparation. For comparison purposes two sample preparation techniques has been included, one ―green‖ (SFE) and one ―non-green‖

(Soxhlet with hexane). Table 18-2 shows the key inventory used; the functional unit employed for comparison has been one analysis, including conditioning time in each technique. The software used for LCA was SimaPro 7.33 (Prè consultants,

Netherland). Data to perform LCA has been taken from two databases Ecoinvent 2.0:

(Life cycle inventory 2007 www.ecoinvent.org) and ELCD database 2.0.

(http://lct.jrc.ec.europa.eu). All the methods studied could be considered as highly green according to the rules used by American Chemical Society Green Chemistry

Institute. The only category that fails is the use of PBT compounds in some of them.

A closer look to the impacts produced by each analysis performed by LCA can provide a better understanding of what lies behind them and the practical consequences of selecting each method.

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A first approach can be performed using a comparative assessment of human toxicity and ecotoxicity of each analytical method. In this sense the use of IMPACT 2002+

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Table 18-2. Key inventory of products considered to perform comparative LCA of analytical methods

HPLC-DAD MECK-DAD UHPLC-MS CE-MS SFC-FID GC-FID Reagents Acetonitrile: 7.96 g Sodium dodecyl Acetonitrile: 0.46 g Ammonium acetate CO2 16 g He 15 g used Water: 16.67 sulfate 0.03 g Water: 3.01 0.02 g H2 0.05 g H2 0.5 g Acetic acid: 0.20 g Sodium deoxycholate Formic acid: 0.01 g Ammonium 0.04g Nitrogen 0.5 g Hydroxyde 0.02 g Boric acid / sodium Water 4 g tetraborate hydrate 2-propanol 0.02 g 0.05 g Nitrogen 0.05 g Water 3 g Nitrogen 0.05 g Column Zorbax C18 column, fused-silica capillary Hypersil Gold column fused-silica capillary fused-silica fused-silica 3.5 μm particle, 4.6 × used was 27 cm (50 mm × 2.1 mm, d.p. used was 27 cm capillary used was capillary used was 150 mm 1.9 μm) 27 cm with SE54 30 m with SE54 Total 45 13 7 25 32 70 analysis time Energy 0.39 kWh 0.16 kWh 0.58 kWh 1.96 kWh 0.81 kWh 2.10 kWh used Wastes Acetonitrile: 7.96 g Sodium dodecyl Acetonitrile: 0.46 g Ammonium acetate CO2 16 g He 15 g Water: 16.67 sulfate 0.03 g Water: 3.01 0.02 g Water 0.2 g Water 0.2 g Acetic acid: 0.20 g Sodium deoxycholate Formic acid: 0.01 g Ammonium As gas As gas In liquid solution 0.04g In liquid solution Hydroxyde 0.02 g boric acid/sodium N2 0.5 g as gas Triethylamine 0.01 tetraborate hydrate g 0.05 g Water 4 g Water 3 g 2-propanol 0.02 g In liquid solution In liquid solution N2 0.05 g as gas N2 0.05 g as gas

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Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 calculation method has been the selected one. IMPACT 2002+ proposes a feasible implementation of a combined midpoint/damage approach, linking all types of life cycle inventory results via 14 midpoint categories to four damage categories (Jolliet et al., 2003). Both human toxicity and ecotoxicity effect factors are based on mean responses rather than on conservative assumptions. In this calculation method all midpoint scores are expressed in units of a reference substance and related to the four damage categories human health, ecosystem quality, climate change, and resources.

As can be seen in Figure 18-10 the use of all the tested methods implies a certain impact, but this impact is much lower than the one associated with sample preparation step. Among the analytical methods studied in the present comparison, the GC-FID analysis of volatiles components of rosemary is the method that provides the higher impacts. Even considering that this method does not use persistent, bioaccumulative, and toxic compounds, that the sample is dissolved in a few ethanol microlitres and the mobile phase is helium, it provides with the higher impacts probably due to the high energy consumption per analysis (mainly by heating the oven at high temperatures).

On the other hand the MEKC-DAD analysis yielded the lower impacts, even considering that several compounds and additives are present in the mobile phase. It is interesting to underline the case of UHPLC-MS, being a method with low impacts able to provide with a lot of information about the sample.

A closer look to each category can be done based on ISO 14044 (ISO 14044, 2006) using well known indicators. The calculation method used can ungroup those categories and the result can be seen in Fig. 18-11. As seen before, MEKC-DAD provided the lowest impacts. One important data to take into account is the higher production of carcinogens by HPLC in comparison to UHPLC, which is due to the

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Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 higher amount of acetonitrile used in each run; nevertheless, other indicators suggest lower impacts.

In general terms the main impacts observed are related to energy consumption of each analytical method. Power supply is the key factor of the energy consumption of analytical instruments and apparatus. The use of high temperature steps (GC) involves a high demand of electricity and contributes to environmental impact of the analytical steps. In this regard, it is clear that the increase of productivity through automation of methods or multianalyte determinations, all contribute to reduce the energy consumption per analysis (de la Guardia et al., 2011c). In this sense it can be concluded that the best analytical method among those compared is UHPLC-MS due to the lower impacts produced running each analysis (short time, low volumes used) but also due to the high information that can be depicted form each run. It meets better than any of the others the Green & omics philosophy.

18.6. Conclusions

As it has been described along this chapter, modern Foodomics approaches include different steps that can be modified to obtain greener processes (see Figure 18-

1).Sustainability and eco-friendliness of a particular process is not just an additional advantage but a goal by itself. In this regard, different approaches have to be closely considered so that greener processes and analytical methods are developed.

One of the main aims is to reduce the use of organic solvents and chemicals that might be toxic and/or hazardous. However, even if this point is of utmost importance,

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Foodomics: Advanced Mass Spectrometry in Modern Food Science and Nutrition (Cap.18): 471-506 (2013) isbn: 978-1-118-16945-2 the necessity of developing processes and methods that are able to consume fewer resources (e.g., power) cannot be underestimated.

Among the sample preparation techniques, modern pressurized extraction methods are pointed out as they are able to provide with additional advantages using significantly less amounts of solvents. Miniaturized extraction methods are also gaining importance in this regard. The development of integrated approaches will also help in the future to obtain more environmentally friendly processes under the Green Chemistry domain.

Simultaneously, different strategies might be followed for samples analysis. Although this part can be less important from a quantitative point of view, several advances have been performed towards greener analytical methods, such as the employment of novel column technologies and the adaptation of conventional methodologies to others using less amount of solvents. Nevertheless, this field will surely continue to evolve in the future in order to develop new greener alternatives for the analysis of complex materials; miniaturization and the use of water at high temperatures could be some of these possibilities.

In general, the development of greener processes and analytical techniques might be further explored through the application of life cycle analysis (LCA). The employment of this useful tool will be increased in the future in a way to efficiently calculate the impact on the environment of the different available procedures. Thanks to LCA, each analytical technique or process might be characterized not only from a throughput perspective but also from a greenness point of view.

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Acknoledgements

M.C.P. thanks MICINN for her ―Juan de la Cierva‖ contract. M.H. would like to thank MICINN for a ―Ramón y Cajal‖ research contract.

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Figure Legends

Figure 18-1. Concepts related to Foodomics. Marked with a star, those concepts that can be greened.

Figure 18-2. Steps of the analytical process to be considered in the frame of

Ecological Paradigm. Reprinted from de la Guardia and Armenta S (2011c) with permission from Elsevier (SciVerse® is a registered trademark of Elsevier Properties

S.A., used under license. Scopus® is a registered trademark of Elsevier B.V.).

Figure 18-3. Evolution of research papers dealing with ―Green Analytical

Chemistry‖. Obtained from Sciverse-Scopus database searching the strings: ―clean analytical chemistry‖ or ―Green Analytical Chemistry‖ or ―environmentally-friendly analytical method‖ (Copyright © 2012 Elsevier B.V.).

Figure 18-4. Basic Scheme of pressurized liquid extractor (A), and supercritical fluid extractor (B).

Figure 18-5. Diagram of extraction processes to obtain antioxidants from rosemary leaves. A) PHWE, B) SFE, and C) Soxhlet.

Figure 18-6. Impact assessment comparison of 1 g of rosemary extract by SFE,

PHWE and soxhlet extraction. Results normalized considering Soxhlet = 100 %.

Figure 18-7. Strategies for greener liquid chromatography.

Figure 18-8. Comparison of typical LC vs CE based on the green analytical concepts.

2012 Elsevier B.V.).

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Figure 18-9. Greenness Profile proposed by The American Chemical Society Green

Chemistry Institute that can be found at http://www.nemi.gov (last accessed May

2012).

Figure 18-10. Comparative assessment of human toxicity and ecotoxicity impacts of each analytical method performed using IMPACT 2002+ calculation method.

Figure 18-11. LCA comparative assessment of impacts derived of each analytical method. Results normalized considering GC-FID = 100%.

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