The Riva Renaissance: Icons of Analytical Innovation — Carlo Bicchi (Part One)

When capillary gas chromatography was still an emerging technology, Carlo Bicchi was among the first in Italy to recognize its transformative potential, particularly for the analysis of plant composition and natural substances: areas that were traditionally constrained by methodological limitations. Rather than treating chromatography as a routine analytical tool, he approached it as a structural discipline: a way to interrogate complexity, resolve stereochemical subtleties, and capture transient molecular events in living systems.

Influenced by the international analytical community, and notably by the example of Pat Sandra, Carlo Bicchi expanded his scope early on. He explored hyphenated techniques when gas chromatography (GC–MS) was not yet standard practice, investigated GC–FT-IR (gas chromatography Fourier Transform infrared spectroscopy) and supercritical fluid chromatography (SFC) long before their current revival, and helped introduce headspace sampling and solid-phase microextraction (SPME) into routine analytical workflows. Yet throughout this technological evolution, capillary GC remained his methodological axis.

Bicchi’s work did not remain confined to the laboratory. From capturing volatiles emitted by living plants to monitoring aroma transfer in industrial food processes, Carlo Bicchi consistently brought analytical chemistry into direct dialogue with biological and technological systems. In doing so, he helped build not only a research program, but a school-one grounded in rigorous separation science, deep chemical understanding, and intellectual independence.

In all this, he never regarded chemistry as subordinate to biology, but rather as its indispensable foundation: the discipline through which the phenomena of life may be rendered intelligible, ordered, and explained in molecular terms. Today, as analytical platforms multiply and technological acceleration challenges both Academia and Industry, his perspective offers a timely reflection on innovation, implementation, and the future of analytical education.

Chiara Cordero: You were among the first in Italy to place your confidence in capillary gas chromatography. What persuaded you at a time when it was far from being an established standard?

Carlo Bicchi: In 1974, after reading Marcel Golay’s paper on the theory of capillary columns and observing the results that leading research groups were beginning to obtain, I resolved almost immediately to orient my work towards this type of column. It was evident to me that the theoretical foundations were sound and that the potential for enhanced resolving power was considerable.

In practical terms, however, I was only able to begin experimental work somewhat later, in 1977, as I had first to overcome certain “environmental difficulties”, a circumstance not uncommon for young researchers at that time. I was fortunate, nevertheless, to receive support from a gas chromatography manufacturer who lent me one of the earliest instruments specifically designed for capillary columns. That opportunity proved decisive.

CC: Applying capillary GC to plants and natural matrices was by no means an obvious choice. What scientific problem were you seeking to address that existing techniques could not adequately resolve?

CB: My conviction was further strengthened by a lecture delivered by Kurt Grob in the mid-1970s. In his studies on tobacco, and particularly on the composition of tobacco smoke, he had succeeded in separating several thousand compounds, even if not all were identified. This achievement was possible only because he had chosen to approach the problem from a fundamentally separative perspective, assigning a central role to the theoretical understanding of the separation process itself.

I was deeply impressed by this approach. It resonated with my own work on plants’ and essential oils’ composition. Through phytochemical studies, I had come to appreciate that any given class of specialised or secondary metabolites within a plant, considered as a biological matrix, could serve as a meaningful representation of the plant’s overall metabolic processes. In essence, it was an early conception of what would later be termed “fingerprinting”, a concept that, from the second half of the 1980s onwards, we also applied within the food sector.

I have always been persuaded that the more thoroughly we know a matrix from a chemical standpoint, the more accurately we are able to characterise and qualify it. This consideration is even more pertinent in the case of plants, whose chemical composition is influenced by a multitude of endogenous and exogenous factors. It therefore became necessary to adopt analytical methods capable of monitoring compositional variation with a separation power far superior to that afforded by conventional packed-column GC.

CC: Looking back, was that decision primarily rational, or did it involve an element of intuition?

CB: It was, above all, a decision born of necessity, grounded in the considerations I have just outlined. My objective was to obtain, wherever possible, the most comprehensive answer from a single analytical operation, i.e. to apply the principle of “one analysis for one problem”, rather than one analysis for “one, or a few, individual compounds”.

In that sense, the choice was more rational than intuitive. I had been trained using packed columns, and the prospect of employing a technique with an efficiency tens of times greater than that to which I was accustomed opened the possibility of addressing applications that would otherwise have remained inaccessible.

As I mentioned earlier, my decision was not universally welcomed. In the first half of the 1970s, capillary columns were widely regarded, not without justification, as unreliable. Yet it was precisely for that reason that I felt compelled to study them in depth, to understand and overcome their limitations. Capillary GC was to become my operative instrument.

“The move towards international engagement marked a decisive intellectual turning point. It was not merely a matter of acquiring new instrumental techniques, but of embracing a broader scientific mentality: innovation understood as a continuous methodological process rather than episodic technical advancement. It is within this framework that the notion of hyphenation emerged, not simply as instrumental coupling, but as the deliberate integration of separation science with spectroscopic identification and, more broadly, as a form of crossed-integration between disciplines.”

CC: How decisive was your encounter with Pat Sandra in shaping the way you conceive analytical chemistry?

CB: In the scientific life of each of us there are individuals who mark our path. For me, in the specific field of capillary GC, figures such as Kurt Grob and Mario Galli were certainly formative. Yet there are others, perhaps unique, who broaden one’s intellectual horizon and reshape one’s approach to research as a whole. For me, that person was Pat Sandra. It is for this reason that, when we speak together,smiling, but very seriously, I address him as Maestro.

What I learned from him above all was the intellectual courage to confront a problem by envisaging the most effective possible solution, even when that solution lay beyond one’s immediate technical competence. If necessary, one studies further; one acquires the knowledge required; and one seeks to apply it in practice in such a way that the analytical process yields the widest and most comprehensive body of information attainable.

Even today, I consider myself Pat’s oldest student, age being merely an administrative fact and not a merit, because I continue to regard the intellectual openness he transmitted to me as a reference point. For the encounter that led to our collaboration, I remain indebted to Albino Sironi, then a young technical manager at Carlo Erba Strumentazione, who made that connection possible.

CC: In what way did that experience encourage you to move beyond capillary GC towards early instrumental combinations such as GC–MS, GC–FT–IR, and SFC?

CB: The answer follows naturally from what I have just said. If more effective techniques exist, or techniques that allow one to view a problem within a broader conceptual framework, or to resolve it more exhaustively, then why should one not explore them?

In the 1980s, for example, I was engaged in studies on plant–insect interactions, particularly concerning pyrrolizidine alkaloids, compounds central to the important multitrophic phenomenon of pharmacophagy. This group of alkaloids included numerous geometric isomers. We were among the first to apply the then nascent modern capillary GC–FT–IR technique for the unequivocal identification of the cis/trans isomers of this class, exploiting diagnostic infrared absorptions characteristic of the different structural forms.

In the 1990s, these same alkaloids would attract considerable attention in the food sector owing to their hepatotoxicity.

CC: At that time, the term “hyphenated techniques” was beginning to circulate. Was it immediately clear to you that the future lay in the integration of separation and identification?

CB: My own engagement with what we would now call analytical platforms dates back to the early 1980s, and to the strategy, developed from 1982 onwards in long discussions particularly with Pat Sandra, of extracting the maximum amount of information from a single analysis.

It should be recalled that GC–MS had been available in routine applications since the mid-1960s. However, the approach was not truly integrated, not least because the first computer systems capable of supporting routine GC–MS operations only became available in the mid-1970s.

In the early 1980s, Pat Sandra already included in his lectures a slide depicting what was then a visionary instrument, arguably one of the earliest conceptualisations of the analytical platform. It illustrated an online sampling system coupled with heart-cut multidimensional GC (H/C-MDGC), simultaneously combined with universal and selective detectors: the flame ionization detector (FID), the electron capture detector (ECD), the flame photometric detector (FPD), and the nitrogen-phosphorous detectror (NPD) and spectroscopic techniques, such as mass spectrometry (MS), Fourier Transform infrared (FT-IR), and atomic emission spectroscopy (AES). The objective was to generate distinct yet combinable datasets, to be merged in data processing, what we would now describe as data fusion, in order to provide an exhaustive description of a complex sample. I myself employed that slide for many years, discussing both its conceptual evolution and its gradual realisation in practice. For me, it was evident that the future of analytical chemistry would not lie in isolated techniques, but in their logical integration, separation and identification conceived as complementary components of a single approach.

“Exploration did not imply dispersion. Throughout successive technological developments, capillary GC remained the structural axis around which methodological evolution occurred. Chiral stationary phases, routine implementation of SPME, integration of sample preparation strategies, and openness to other high-concentration capacity (HCC) extraction techniques were not deviations from a core identity, but its natural extensions.”

At the heart of this coherence lies a simple conviction: separation is not merely an instrumental step, it is a methodological culture.

CC: Despite exploring new technologies, capillary GC has always remained your central axis. What makes this technique still pivotal today?

CB: As I have mentioned previously, the focus of our research activity has been volatiles and their role as the “identity card” of natural matrices. Capillary GC and its derived techniques, GC×GC, heart-cut multidimensional GC (H/C-MDGC), and preparative capillary GC, remain the most efficient and reliable analytical approaches for these compounds, particularly as matrix complexity increases.

No other technique currently possesses the capacity to separate more than ten thousand compounds in a single analytical run, as GC×GC demonstrably can. Even with present performance levels, capillary GC occupies a central position in volatile analysis. Yet I am convinced that its full potential remains only partially expressed.

There is considerable room for further development, particularly in specialised and industrial applications, for example, in portable GC systems and micro-GC instruments based on micro-electromechanical (MEMS) chip technology. Moreover, novel stationary phases based on different analyte–phase interaction mechanisms merit deeper investigation. Ionic liquids, in my view, still represent an insufficiently explored opportunity.

Equal attention should be devoted to the development of more energy-sustainable instrumentation (not only through broader adoption of fast GC methodologies) and optimization of the heated volumes involved in the three fundamental components of the GC system (injector, oven, and detector[s]), but also through the extension of hydrogen as carrier gas into routine GC–MS applications.

CC: You were among the first to introduce SPME into routine practice in Italy. In volatile analysis, how important is the structural integration of sample preparation and separation?

CB: I consider it fundamental. The concept of the total analysis system (TAS), introduced by Manz in the early 1990s, represents in my view the logical evolution of complex mixture analysis. Sample preparation, separation/detection, and data processing are not independent stages, but components that must be physically and conceptually integrated into a unified analytical process.

The guiding principle in sample preparation should be: “the best sample preparation is …. no sample preparation”. Although I fully recognise that this ideal cannot be entirely realised in practice, it should nonetheless orient method development.

At the beginning of my career, and regrettably in many cases still today, official methods prescribed the use of hundreds of millilitres of solvent or grams of sample to isolate a fraction, only to inject one microlitre of that extract into the analytical system. This is fundamentally irrational. Overcoming this paradox required substantial research effort, which ultimately led to the development of microextraction and high concentration capacity (HCC) techniques, including solid-phase extraction, (SPE), solid-phase microextraction (SPME), stir bar sorptive extraction (SBSE), headspace sorptive extraction (HSSE), sorptive tape extraction (STE), and solid phase dynamic extraction (SPDE). We are now approaching an interesting conceptual inversion: whereas traditionally sample preparation was adapted to the subsequent analytical technique, increasingly the analytical technique is selected or adapted according to the optimal sample preparation strategy. This reflects a mature understanding of analytical design.

CC: The development of chiral stationary phases in GC represented both a technical and a conceptual challenge. How important is it, for an analyst, to understand the chemistry of the stationary phase beyond its chromatographic performance?

CB: The three-dimensional form of molecules has always fascinated me. In phytochemical studies, I was repeatedly struck by the stereospecific nature of biochemical processes within plants. It is almost as though each species safeguards its uniqueness through stereospecific processes, which in turn governs its interaction with the surrounding environment.

We encounter stereospecific biological interaction daily. Enantiomers of a volatile chiral compound may exhibit entirely different sensory properties, a clear demonstration that molecules differing only in spatial arrangement interact differently with olfactory receptors.

Analytically, three circumstances directed me towards chiral separations of volatile compounds. First, a 1984 publication by Gerard Schomburg and Wilfried König, two researchers for whom I had great respect, in which they separated the enantiomers of the four menthol isomers by H/C-MDGC, albeit after derivatisation into the corresponding diastereoisomers. Second, extensive discussions with Thomas Koscielsky, collaborator of Danuta Sibińska in Warsaw, who in the same period showed me their enantiomeric separations of pinanes and caranes on packed columns using cyclodextrins as chiral selectors. Third, long conversations with Volker Schurig on complexation chromatography.

My objective became to render enantioselective gas chromatography routine, employing derivatised cyclodextrins as chiral selectors for the direct separation of enantiomers, that is, without diastereomeric derivatisation. This had clear practical implications, for example in quality control within the essential oil and perfume industries.

In keeping with the methodological formation I received from Pat Sandra, my ambition was to move from the concept of “one column for one compound” to “one column for one problem” in enantiomeric analysis. In 1988 we prepared our first column incorporating a derivatised cyclodextrin(a permethylated cyclodextrin) as chiral selector.

All this leads me to a very direct answer to your question: yes. Mastery of a technique, and in this case, of its chemical foundations, exponentially increases one’s capacity to exploit its full potential. It was for this reason that, in 1982, despite certain practical and “environmental” obstacles, I resolved to learn column technology myself. If capillary GC was to become my daily instrument, then I had to possess the technique not only intellectually, but also practically, in my fingers.

Taking instrumentation into real biological and industrial processes marked a further methodological shift. Analysis was no longer confined to controlled laboratory environments, but embedded within dynamic systems — living plants, ecological interactions, industrial plants — where variability itself became part of the problem.

Biography

Carlo Bicchi has been Full Professor of Pharmaceutical Biology at the University of Turin since 1990. In the same University, he was Director of the Department of Scienza e Tecnologia del Farmaco and Dean of the Faculty of Pharmacy. Main field of research: development of capillary GC and GC-MS and analytical technologies mainly focused on biologically active specialized metabolites in vegetable matrices (mainly essential oils, and plant volatiles) and aroma profiling and fingerprinting of important industrial food crops (coffee, cocoa, hazelnuts, olive oil and tea). Main topics: Sample preparation; capillary-GC and GC-MS, Fast-GC, GC-GC and GCxGC, Enantioselective GC, HPLC and HPLC-MS, SFE and SFC. Data handling: chemometric methods for volatilomics and sensomics.

Chiara Cordero is Full Professor of Food Chemistry at the Department of Drug Science and Technology, University of Turin (Italy). Her research focuses on the development and optimization of comprehensive two-dimensional gas chromatography (GC×GC) platforms for food-omics, including profiling and fingerprinting, advanced data processing strategies, and the identification of food quality and dietary intake markers through metabolomics and volatilomics within nutrimetabolomics. She also develops miniaturized, automated, solvent-free sample preparation methods for sensomic analysis. Her work has received international recognition, including the Leslie S. Ettre Award (2008), the John B. Phillips Award (2014), inclusion in The Analytical Scientist Power List (2016, 2025), the Scientific Achievement Award in GC×GC (2022), and the Giovanni Dugo Medal (2024).

Further Information
The 44^th international Symposium on Capillary Chromatography (ISCC) and 21^st GC x GC Symposium takes place from May 17–22 2026 at the Conference Centre, Riva Del Garda, Italy. For more information on the scientific programme and conference events, please go to: https://iscc44.chromaleont.it/