We are happy to share that the CMF’s Health for Hungary program reached new milestones, as on 26th of September 2022, the study enrolled the 5000th individual making the overall number of samples more than 7300. As new people are joining, and our database is getting bigger, we are glad to see that the willingness to stay part of the research and donate blood samples from time to time is getting stronger, which is a crucial factor in our method. Nothing proves this better than the fact that on 26 September 2022, one of the participants gave a blood sample for the 4th time.

We are continuously working to bring the H4H program closer to more and more people. In September 2022, we expanded our sampling center network, so now, 17 centers in 13 cities across Hungary have permission to collect blood samples as part of the H4H program.

We are happy to see the growing number of H4H participants and new sampling centers joining, which step by step brings us closer to developing a novel personalized infrared laser-based diagnostic tool for the future of healthcare.

Every autumn, the research groups of the Attoworld meet under the leadership of Prof. Ferenc Krausz in their Attoworld-meeting on the research campus Garching. From September 20 to 22, 2022, the scientific group leaders presented the current results of their research with a view to the progress achieved in the past year and gave an outlook on the future development of their research area. For the "Center for Molecular Fingerprinting" (CMF), Dr. Mihaela Žigman, leader of the department "LIFE SCIENCE," and Dr. Alexander Weigel, head of "LASER SCIENCE" gave their presentations. Both are working closely with their groups on the detection and scientific evaluation of molecular fingerprinting for the early diagnosis of diseases.

The event served not only to provide information but also to stimulate lively and result-oriented discussions among experts. And even away from the lectures, there was an opportunity for vivid exchange and strengthening of bonds. Thus, the meeting ended with a joint hike around the Upper Bavarian Schliersee to get the heads free again for new inspirations. One can, therefore, already be curious about the results and scientific advances in the coming year.

In an invited contribution at the 10th Europhoton Conference in Hannover (28th August until 2nd September 2022), Dr. Philipp Steinleitner, who is working in close cooperation with the CMF Laser Science Team led by Dr. Alexander Weigel, has just presented the results he obtained together with Nathalie Nagl (LMU) and Maciej Kowalczyk (CMF). He showed how to generate extremely stable infrared pulses comprising only a single oscillation cycle of the light electric field and how to control their waveform.

More details about this work based on our new Cr:ZnS laser platform can be found in our latest Nature Photonics publication: https://www.nature.com/articles/s41566-022-01001-2

The editors of Nature Photonics have taken the occasion of this year's award of the Wolf Prize to Paul Corkum, Anne L'Huillier and Ferenc Krausz to shed special light on Attosecond physics. CMF's laser systems for infrared spectroscopy of blood samples are also based on this fundamental research. The editors welcome this year’s award, which pays tribute to the growth that Attosecond science has experienced in the last decades. In Nature Photonics they celebrate the award with interviews with the three prize winners, who share their views on the development of the research field, the unanswered questions and the exciting opportunities laying ahead.
Read more: here and here.

Gaining a biobank license is an important step forward in CMF’s life.

CMF started the application process for a biobank license earlier this year, and we are proud to announce that after an inspection on the 20th of July, the NNK (National Public Health Center) has granted the license for our interim biobank at Szeged. Our new biobank is equipped with 2 -80 °C ultradeep freezers with a storing capacity of 40 000 aliquots per equipment. To ensure sample security, one of the freezers serves as a backup. In case of an emergency, text message and email is sent to Biobank operators to give enough time to save samples. Gaining a biobank license is an important step forward in CMF’s life.

From June 11-15, 2022, the 8th International Conference on Attosecond Science and Technology was held at the University of Central Florida in Orlando. In advance of the expert conference on ultrashort pulse physics, more than 300 scientific papers have been submitted by experts researching this subject. The conference kicked off last Monday with a tribute to this year’s Wolf Prize winner in physics. Anne L'Huillier, Paul Corkum, and Ferenc Krausz, all luminaries in the field of attosecond physics, gave a talk on their current research. Under the title “Attosecond Metrology 2.0: From Tracking Electronic Motion to Probing Human Health“, Ferenc Krausz, Director at the Max Planck Institute of Quantum Optics and Professor of Experimental Physics at the LMU as well as Scientific Director at the Center for Molecular Fingerprinting (CMF) in Budapest, gave a virtual lecture on his primary research and that of his research groups in the field of ultrafast physics. There was a particular focus on the promising applications in the early medical detection of diseases such as cancer, which can be detected at the molecular level using laser-based infrared spectroscopy. Krausz is working on this research with parts of his attoworld team and CMF in Budapest.

Nathalie Nagl, who currently works as part of the AMPiii and CMF Laser Research teams on making the vision of probing human health with attosecond metrology reality, also gave a presentation on “Single-cycle infrared waveform generation and control”. Together with Philipp Steinleitner and Maciej Kowalczyk, also main authors of this work, she demonstrated a new, extremely broadband, stable single-cycle infrared laser source with control over the waveforms of the emitted pulses. For her PhD thesis on the development of the laser driving this unique source, she recently received the Otto Hahn Medal of the Max Planck Society. This is the eighth time the conference has brought together leading experts in the science of attosecond physics and provided a forum for the latest research results and discussions.

(© Attoworld )

The 12th International Conference of Clinical Spectroscopy was held in Dublin from June 19-23, 2022. In her presentation “Electric-field molecular fingerprinting of blood: new prospects for probing human health“ Dr. Mihaela Žigman, head of the attoworld research group BIRD (Broad Band Infrared Spectroscopy) at the Ludwig-Maximilians University of Munich and Research Director at the Center for Molecular Fingerprinting (CMF) in Budapest, presented current research results in laser-based infrared spectroscopy and its promising applications in the field of diagnostic early detection of diseases at the molecular level in the presence of an international audience of experts.

Asked about her impressions of the biannual conference, Dr. Žigman stated, "Due to the global COVID pandemic, the event had to be cancelled last time. I am pleased that the conditions were now in the proper state again for the SPEC conference to be held in person this year. The event was very interesting and educational for all participants!"

Original publication:
Mihaela Žigman and Ferenc Krausz "Electric-field molecular fingerprinting of blood: new prospects for probing human health", Proc. SPIE 11655, Label-free Biomedical Imaging and Sensing (LBIS) 2021, 116550Z (5 Ma 2021); https://doi.org/10.1117/12.2587329

Abstract:
Recent advances in ultrafast laser science have opened new prospects in probing living systems. Suddenly-excited molecular vibrations emit picosecond-duration coherent infrared light characteristic of the sample’s composition. Given the capacity of this electric-field molecular fingerprint (EMF) to cross-molecularly probe organic samples, we evaluate the feasibility of EMF for biomedical diagnostics. We report high stability of EMF over time and show that several cancer entities leave their signatures in the EMF of serum. Leveraging on the advances of stability, reproducibility and sensitivity of EMF, we provide foundation for applications of infrared molecular profiles in the preventive care model of health monitoring.

In mid-March, we reported that Dr. Nathalie Nagl, a physicist at the Max Planck Institute of Quantum Optics (MPQ) in Garching near Munich, would be honored with the Otto Hahn Medal, an award for early achievements in the field of physics, for her outstanding research results in the course of her doctoral thesis. The ceremony took place at the Max Planck Society on June 22, 2022 in Berlin. Dr. Nagl received the award from Prof. Klaus Baum, Vice President of the Chemical-Physical-Technical Section of the Society.

Nagl receives the prize for the development of femtosecond lasers in the mid-infrared spectral range, which will significantly accelerate the widespread application of novel spectroscopy techniques in biomedicine. This new laser technology (diode-pumped Cr:ZnS lasers), which Nagl developed as part of her doctoral thesis, will be the basis for all of CMF's new infrasampler laser systems (ISA3.0). Dr. Nathalie Nagl was therefore recently appointed "project leader" for ISA3.0 and will be responsible for completing two systems based on the laser technology she developed by the end of this year.

Ferenc Krausz received his honorary award at the Wolf Prize Ceremony 2022 in Israel at the Knesset on June 16.

After the winners of the Wolf Prize were announced in February 2022, the awards were ceremonially now presented on Thursday, June 16, in the Knesset, the unicameral legislature of Israel. Our whole team would like to congratulate Ferenc Krausz again, who, together with Anne L'Huillier and Paul Corkum, received the Honorary Award for Physics this year. The jury justified the prize to Ferenc Krausz "for pioneering contributions to ultrafast laser research and attosecond physics". In his acceptance speech, the awardee thanked his current and former team members for their joint success and his family, especially his wife, for their heartfelt support. He also announced his intention to donate the prize money to the initiative science4people.org, which he launched with team members under the worrying impressions of the war in Ukraine. Together with aid organizations such as the youth organization STAN, this cross-border project of scientists is currently working in war-torn Ukraine to help the needy and refugees, especially in education, which is presently often denied right now. More projects in other oppressed regions will follow in the future and be made possible by generous donations like this one.

In cooperation with the Budapest University of Technology and Economics the analysis of the molecular composition of human blood using ultra-short pulse laser technology can be realized in Hungary.

Prof. Ferenc Krausz, Scientific Director of the CMF, studied electrical engineering at the Technical University of Budapest and theoretical physics at the Eötvös Loránd University. "As a student, I attended wonderful lectures at both institutions. I had outstanding researchers and teachers who left a legacy of professional achievements that have influenced the lives of generations," he said of his mentors György Marx at ELTE and Károly Simonyi at BME.

Ferenc Krausz and his research group are currently investigating the medical diagnostic potential of short-duration light pulses. The renowned physicist initiated the establishment of the Center for Molecular Fingerprinting (CMF) in Hungary 4 years ago. Thanks to the support of the Minister of Innovation and Technology László Palkovics and the Hungarian government, the research center was established in May 2019 under the auspices of the Ministry of Innovation and Technology (ITM).

CMF's H4H Health for Hungary - Hungary for Health research project aims to use artificial intelligence to discover which diseases can be deduced by doctors from the infrared molecular fingerprints generated during blood analyses.

"We need a large number of samples to document the molecular abnormalities caused by each pathological lesion. To this end, we have set up the H4H Health for Hungary - Hungary for Health program, in which we plan to conduct a series of clinical trials involving 15,000 subjects over 5 years in the first phase. Participants in the program will be asked to donate blood several times a year. The first few times will be used to determine the personalized normal (healthy) range of the molecular fingerprint. Then the follow-up tests will monitor whether the fingerprint remains in this range or leaves it permanently," said Ferenc Krausz, explaining the promising potential for improving the quality of human life.

As a first step in the implementation of the project, CMF plans to set up a temporary laboratory for laser research and analysis of blood samples. Intensive discussions are currently underway with the Chancellor's Office of the University of Technology to set up the temporary laboratory. The long-term research base of the CMF is planned to be built in the next few years on the vacant site between the Budapest University of Technology and Economics building I and the Eötvös Loránd University TUT facility in Lágymányos.

The full interview is available in Hungarian here.

Ultrashort infrared light pulses are the key to a wide range of technological applications. The oscillating infrared light field can excite molecules in a sample to vibrate at specific frequencies or drive ultrafast electric currents in semiconductors. Physicists from the attoworld team at the Ludwig-Maximilians-Universität München (LMU), the Max Planck Institute of Quantum Optics (MPQ) and the Center for Molecular Fingerprinting (CMF) have now succeeded in generating ultrashort mid-infrared pulses and precisely controlling their electric-field waveforms. The basis for the new mid-infrared source is a stabilized laser system that generates light pulses with a precisely defined waveform at near-infrared wavelengths. The pulses consist of only one oscillation of the light wave and are thus only a few femtoseconds long (a femtosecond being one millionth of a billionth of a second, 10-15 s). The team utilizes frequency-mixing processes in nonlinear crystals to translate the near-infrared pulses into controllable infrared waveforms. With this infrared waveform manipulator at hand, new possibilities of optical control for biomedical applications and quantum electronics come into reach.

The article is available in here or download the short version in pdf.

Prof. Ferenc Krausz, Scientific Director of CMF, gave an interview to one of the major Hungarian newspapers, Magyar Nemzet.

"No time for daydreaming!" - he said in the interview. Prof. Krausz has recently turned 60 and is very conscious of spending the time he has on the most important things.

As head of the Center for Molecular Fingerprinting in Budapest, he explained in the article how his research focuses on the molecular fingerprinting of blood to develop a new generation of molecular diagnostics. The stakes are huge. The technique has the potential to become a cornerstone of future preventive healthcare, creating exceptional value for individuals and society.

The feature also mentions that in his spare time, Prof. Krausz has mobilized his international network of contacts to launch a fundraising campaign (www.science4people.org) to help those affected by war.

The full interview is available in Hungarian here or download pdf.

Not a long time ago, in April, the analysis of the first 560 subjects of the H4H study was accepted by ETT-TUKEB (Medical Research Council Scientific and Research Ethics Committee), which was a requirement to continue the project. After a short break, sample collection has restarted in April, and it is clearly visible that the willingness to participate in our research has strongly increased in the last month. On 5 May, the study enrolled the 1500th individual making the overall number of samples 2000 (with 500 returns).

We have also expanded our sampling center network as twelve new ones have been granted permission to collect blood samples as part of the H4H project. These new centers will slowly start receiving volunteers in the next few months, bringing H4H closer to more and more people across Hungary.

We are happy to see the growing number of H4H participants and new sampling centers joining, which step by step brings us closer to developing a personalized infrared laser-based novel diagnostic tool for the future of healthcare.

Prof. Ferenc Krausz will give a talk on Friday, 29.4.2022, from 20.00 to 21.00 (CET) with the title: Attosecond Metrology 2.0: From Tracking Electronic Motions to Probing Human Health at the Wolf Prize in Physics Seminars in NRC University of Ottawa

Our Scientific Director and Wolf Prize Laureate of 2022 Prof. Ferenc Krausz will give a virtual expert talk on his research area of attosecond physics and its potential applications in the field of medical preventive health care on Friday, 4/29/2022 from 8:00 pm-9:00 pm. The talk is part of the National Research Council Canada's Wolf Prize Seminar at the University of Ottawa.

Anyone interested has the opportunity to attend the richly illustrated talk via the following zoom link:

https://us02web.zoom.us/j/87081548366?pwd=b0NTbzVUSWViMVFHc1AreXZwQS9iQT09

Meeting ID: 870 8154 8366
Passcode: 232392

Abstract: Next-generation attosecond metrology (2.0) relies on sub-fs charge carrier injection into wide-gap materials. The injected carriers can be used to directly probe fundamental processes of ultrafast optoelectronics and sample optical fields up to PHz frequencies. Light fields from the infrared to the ultraviolet, with accurately measured temporal evolution, serve as a unique probe for the polarization response of matter. Field-resolved spectroscopy will access valence electronic as well as nuclear motions in all forms of matter and constitutes a generalization of pump-probe approaches. The multi-MHz-rate synthesis and measurement of infrared waveforms with 1-attosecond-scale precision opens the door for real-world applications. They include probing of human health by measuring miniscule changes of the molecular composition of blood (liquid biopsy) via field-resolved vibrational molecular fingerprinting.

Bio: Prof. Ferenc Krausz earned his degree in Electrical Engineering at the Technical University Budapest (1985). He completed his doctorate in laser physics at the Technische Universität (TU) in Vienna (1991) where he continued in the same research field in 1993, took up assistant professorship in 1998 and full professorship in 1999. In 2003, he was appointed Director of the Max-Planck-Institute of Quantum Optics (MPQ) in Garching. In October 2004, he became professor at the Faculty of Physics of Ludwig-Maximilians-Universität (LMU) in Munich and has since then held the Chair of Experimental Physics – Laser Physics. In a series of experiments performed between 2001 and 2004, Ferenc and his team succeeded in producing and measuring attosecond light pulses and applying them for the first real-time observation of atomic-scale electronic motions. These achievements earned him the reputation as the co-founder (along with Paul Corkum) of the field of Attosecond Physics, a scientific discipline devoted to real-time observation and control of electron phenomena, as also acknowledged by their selection as 2015 Thomson Reuters Citation Laureates. More recently, he turned his attention to capitalizing on ultrafast laser techniques for disease detection by the molecular fingerprinting of human bio-fluids.

A brief introduction

Today we would like to briefly introduce the CMF Laser Science Team and what they are currently working on.

Our international team, led by Dr. Alexander Weigel, combines laser and metrology development with engineering to develop new instruments for future health monitoring with field-resolved infrared spectroscopy.

As the future laser platform, we develop ultrafast Cr:ZnS oscillators, which are directly pumped by low-noise laser diodes. Aleksandar Sebesta and Arun Paudel have just completed a first engineered laser prototype, which produces few-cycle pulses at 2.4 µm with a new level of power stability. Together with Matthias Stadter, our mechanical engineer, they are already working on the next-generation laser prototype, which will form the basis for the new metrology system. Meanwhile, Dr. Maciej Kowalczyk stabilizes the carrier envelope phase of these lasers to record-low levels. In order to boost the output power further, Dr. Shizhen Qu develops Cr:ZnS amplifiers with low-noise diode-pumping technology. Yudong Sun assists with laser characterization. We will use these unique sources for multi-octave-spanning mid-infrared generation and record the infrared response of human blood samples with field-resolved detection.

Simultaneously, we are already pushing the field-resolved infrared measurement technology using systems based on high-power Yb:YAG thin-disk lasers. Dr. Christina Hofer currently coordinates the upgrade of such a system to kHz-rate optical scanning using two synchronized laser oscillators. Dr. Sebastian Gröbmeyer uses nonlinear compression to achieve broader bandwidth in the infrared pulses and extract more information out of the biological samples. Dr. Abhijit Maity, Dr. Wolfgang Schweinberger, and Dr. Dionysios Potamianos work on the detection with ultra-rapid electro-optic sampling. Hojjat Heydarian from the ACCORD team supports us with the development of new detector electronics. Our computer scientist, Patrik Karandušovský, develops algorithms for high-speed delay calibration of the dual-oscillator scan with attosecond precision. In March 2022, the system will move to the CMF National Laboratory in Hungary, where it will be used to analyze blood samples and identify disease-specific infrared fingerprints.

A conversation with the Wolf Prize laureate 2022

Prof. Ferenc Krausz, a coriphae in the field of attosecond physics and Scientific Director of CMF, was awarded the prestigious Wolf Prize 2022 in February. On the occasion, he currently gave an exclusive interview to iGlobenews magazine. Herein, Prof. Krausz talks about the basic research of ultrashort pulse laser physics and its concrete application possibilities, which are emerging in the field of personalized preventive healthcare, developed in collaboration with the Center for Molecular Fingerprinting. You can currently read the whole interview in English here or as a pdf.

New study has been launched to detect pancreatic, liver or colon cancers

Is infrared molecular fingerprinting useful for detecting gastrointestinal tumors? That's what the Lasers4Life team (L4L), a key CMF collaboration partner in Germany, is trying to find out for the first time in a new study. The project has now been launched at the University Hospital of Tübingen, one of the world's leading universities for life sciences, and medicine in the center of Baden-Würtemberg. The researchers have already proven that the method of infrared molecular fingerprinting has the potential to detect different types of cancer (eLife 2021; DOI: https://doi.org/10.7554/eLife.68758 ). But can infrared spectroscopy also be used to detect pancreatic, liver or colon cancers? That has not yet been studied experimentally. The pilot project "Laser-based detection of gastrointestinal tumors and their recurrences" is being carried out by the L4L team in collaboration with the Medical Clinic, Internal Medicine I, of the University Hospital Tübingen (UKT). The researchers will use infrared spectroscopy to analyze blood samples from cancer patients for their molecular composition. Both the conventional FTIR method and, in parallel, the infrared laser spectroscopy newly developed in collaboration with CMF will be used. The aim is to investigate whether molecular infrared fingerprinting can be used as a new, non-invasive method for the efficient examination of human blood to detect cancers of the gastrointestinal tract. An exciting start to an ambitious project and a new collaboration!

Dr. Nathalie Nagl honoured with the Otto Hahn Medal of the Max Planck Society

Dr. Nathalie Nagl, a physicist at the Max Planck Institute of Quantum Optics in Garching near Munich, will be honored with the Otto Hahn Medal of the Max Planck Society for the year 2021. The award is given in recognition of outstanding achievements from the first creative period of young scientists. Nagl will receive the award for developing femtosecond lasers in the mid-infrared spectral range, which will significantly accelerate the broad application of novel spectroscopy techniques in biomedicine. This new laser technology (diode-pumped Cr:ZnS lasers), which Nagl developed during her doctoral research, will be the basis for all of CMF's new infrasampler laser systems (ISA3.0). As a result, Dr. Nathalie Nagl has recently been appointed "project manager" for ISA3.0, and she will be responsible for completing two systems based on her developed laser technology by the end of this year. The medal will be awarded to Nathalie at the annual meeting of the Max Planck Society during the meeting of the Chemistry, Physics, and Technology Section on Wednesday, June 22, 2022, in Berlin. We warmly congratulate Dr. Nathalie Nagl on this highly deserved award!

The presentation "Infrared sensing as a new monitor of health" at the Deutsches Museum in Munich

An exciting evening was experienced by the guests on March 9, 2022, in the Hall of Honor of the Deutsches Museum in Munich. It is the world's largest museum of science and technology, which regularly offers an extensive accompanying program on current research topics. In her presentation "Infrared sensing as a new monitor of health", Dr. Mihaela Žigman, Research Director at CMF and head of the BIRD (Broadband Infrared Diagnostics) research group in the attoworld team, gave insights and outlooks into the field of her research area on molecular fingerprint detection and analysis.

She explained to the interested audience how ultrashort pulse laser technology could be used in the future in medical applications for the early diagnosis of diseases such as cancer and highlighted the first promising research results. She also provided a detailed presentation of the large-scale Lasers4Life and H4H (Health for Hungary) studies in Germany and Hungary. A question and answer session at the end of the lecture showed the great interest of the audience and brought the informative evening to a successful close.

The presentation in German can be viewed on the youtube channel of the Deutsches Museum:

https://www.youtube.com/watch?v=SblAhdYc8og&list=PLqvZktQdyL4teBsJsb7Sn2pCLdnJLQEXv

Extensive efforts by the CMF, LMU and MPQ teams have been advancing together the frontiers of laser science over the last years. But we are turning on a new page here: The time has come to finally apply and evaluate the latest technological advances for its possible applications in medicine. And the quest to evaluate whether Infrasampler 1.5 technology will level up in vitro cancer diagnostics is on!

In a joint effort, scientists from the Max-Planck-Institute for Quantum Optics (MPQ), the Ludwig-Maximilians University Munich (LMU) and the Center for Molecular Fingerprinting Research (CMF) have developed the Infrasampler 1.5 - a new device for field-resolved molecular fingerprinting of human blood samples. Proudly and excitingly - the first pilot application on human blood serum just started. Here the performance of the new laser-based spectrometer will be evaluated to identify molecular fingerprints specific to prostate, breast and lung cancer.

The Infrasampler 1.5 uses ultrafast high-power lasers from the LMU research laboratories to create mid-infrared pulses and excite the molecules in the human, blood-based samples. Imagine the event like a mallet hitting a gong: With the ultra-sensitive field-resolved detection the new capacity to listen to the ringing that follows the gong is available. And the recorded echo-like signatures from human serum are characteristic to the molecular composition of the sample. Now the quest is to figure out whether these signals from human samples are corelating with human physiologies and diseases like cancer.

The metrology has been developed by the team around Dr. Ioachim Pupeza, group leader of the field-resolved metrology development, who has teamed up with the group around Dr. Alexander Weigel, chief laser scientist. They are grateful for contributions of Philip Jacob, Phd student, Dr. Christina Hofer, non-linear optics expert, along with the support of Dr. Wolfgang Schweinberger, senior scientist. Developing this new technology was a truly multi-disciplinary endeavor and required scientists and experts from fields as diverse as laser physics, nonlinear optics, computer science, data analysis and bioengineering to work together.

But these are not all. For the whole endeavor even more professionals are intricately networking here. On the computer scientist side, Patrik Karandušovský is developing the algorithms and control programs for the system, while Dr. Maximilian Högner, postdoctoral scientist, developed data analysis procedures. And getting to molecular level, the broadband infrared diagnostics (BIRD) team around Dr. Mihaela Zigman is enabling the biological and even real-world clinical settings to be evaluated. It is the expertise of Dr. Michael Trubetskov, Dr. Kosmas Kepesidis, Dr. Marinus Huber, Dr. Frank Fleischmann, Eric Grießinger that is after the molecular fingerprint echos, which they are correlating with the medical parameters, managed by the clinical study team around Jacqueline Hermann.

What is new within the Infrasampler 1.5 technology? Compared to previous similar instruments, Infrasampler 1.5 is now equipped with a new ultra-rapid scanning technology, which enables us to record up to 3000 measurement scans per second, compared to previously just one trace per second. A new milestone in the field. The vision is to use the Infrasampler technology as a standardized technique for future medical applications, and the launch of the first Infrasampler 1.5 measurements is another important milestone on the way.

The path for shaping the future of healthcare may be challenging, with many multi-level problems to be tackled. Even so, the cross-disciplinary strength and the power of great minds from LMU, CMF and MPQ acting in such unison while pursuing the mission may turn out imperious. For the future of technologies involved, as well as their applications.

On 14 February, the Minister of Innovation and Technology László Palkovics and Dr. Ferenc Krausz held a press conference at the Ministry of Innovation and Technology. Minister Palkovics took the opportunity to congratulate Ferenc Krausz on the recently awarded Wolf Prize for his pioneering work in the field of ultrafast laser science and attosecond physics. László Palkovics said that the government has for years considered the health economy to be the key to Hungary's economic competitiveness, so it is no coincidence that the Ministry of Innovation and Technology is a committed supporter of the research carried out at the Center for Molecular Fingerprinting.

Ferenc Krausz then presented the CMF's research program, which aims to detect early cancer and other diseases using an innovative method of infrared molecular fingerprinting. Dr. Krausz highlighted that they plan to test blood samples from 15,000 participants over the next 10 years, requiring donors to give blood 1-3 times a year, so that differences between participants and changes within individuals can be tracked.

Prostate cancer, the leading type of cancer in men, is still challenging to be diagnosed at an early stage when mostly asymptomatic or indistinguishable from other urinary problems. The current methods for reliably detecting and distinguishing early prostate cancer lesions are not feasible without tissue biopsies. A new infrared spectroscopic method could be a game-changer to analyze exprimate urine. Non-invasive and without radiation hazard.

Very close collaborators of CMF – from the Broadband Infrared Diagnostics (BIRD) team at the LMU Munich - just initiated a new clinical study entitled "Infrared Spectroscopy of Blood and Exprimate Urine for Prostate Cancer Detection". This clinical trial is set to provide proof of concept for the ability of a drop of exprimate urine as a new test to reveal the presence of prostate cancer. The study is inherently interdisciplinary, combining laser physics, molecular biology, and prostate oncology efforts. It was initiated at the end of January at the Ludwig Maximilans University (LMU) Hospital, Department of Urology in Munich. At the clinic, Dr. Michael Chaloupka leads the program managed by the BIRD clinical trial team. They have defined the study's framework and successfully enrolled the first participating patients!

In addition to the clinical team in the hospital at Grosshadern, located south of Munich, the investigations are going on in the north of Munich, at the LMU in Garching, just as well. The researchers of the BIRD team are applying the latest advances in infrared spectroscopy and ultrashort pulsed lasers to build a prostate cancer detection test - based on infrared molecular analysis of human exprimate urine so they can compare the molecular makeup of exprimate urine and blood plasma from patients with prostate cancer with those from control individuals.

Infrared fingerprinting analyzes organic molecules to decipher healthy and prostate cancer states by studying the dynamic biochemical suite found in the bodily fluids. With its altered physiology and pathology, the presence of prostate cancer can cause changes in the exprimate urine, and this is where the new approach comes in: The researchers will measure infrared profiles using infrared spectroscopy on the samples coming from the clinic. They have a new tool, an ultrashort pulsed laser device, that can examine an array of compounds by measuring the collective infrared molecular fingerprints within a single measurement only.

It is up to the future results to see whether the infrared molecular fingerprints of exprimate urine from men with or without prostate cancer are any different. The quest for testing the new technology and thus the new way of sensing prostate cancer is on, and the efforts are set afloat!

1000 volunteers have already joined our cutting-edge research program.

The H4H (Health for Hungary - Hungary for Health) project aims to develop an infrared laser-based novel diagnostic tool to provide personalized healthcare to each person’s unique biology and identify diseases before the symptoms arise.

An essential part of the research is the collection of blood samples from healthy individuals voluntarily; therefore, it is important that we reach a wide range of people over the next 10 years. We ask our volunteers to visit us 2-3 times per year. This way, the differences between individuals, as well as changes within the individuals can be described and analyzed.

The collection of blood samples has started in the summer of 2021, and we are proud that we can already announce that the 1000th volunteer has joined the research program. Currently, there are 11 collaborating institutions in Hungary where people can participate but the list of our partners is constantly expanding as we want to bring this research program close to as many people as possible.

We are incredibly grateful for all the volunteers who have trusted us and participated so far. We wish to thank all our colleagues and partners whose hard work and dedication have made this possible, and we look forward to continuing the research together - for advancing the future of healthcare!

For more information and participation details, please visit our www.h4h.hu website.

Ferenc Krausz has been awarded the prestigious Wolf Prize for his pioneering contributions to ultrafast laser science and attosecond physics

Ferenc Krausz is Chair of Experimental Physics - Laser Physics at Ludwig Maximilians University of Munich and Director at the Max Planck Institute of Quantum Optics and Scientific Director at the Center for Molecular Fingerprinting (CMF) in Hungary.

In 2001, Ferenc Krausz and his team at the Vienna University of Technology succeeded for the first time in experimentally generating and measuring single flashes of extreme ultraviolet light that were only attoseconds long (an attosecond is one-billionth of a billionth of a second). The results marked the beginning of attosecond physics and set a milestone in science. The attosecond light flashes made it possible for the first time to visualize the ultrafast motions of electrons, to photograph them, so to speak. In recent years, Ferenc Krausz and his colleagues have succeeded in making numerous real-time movies of the motion of electrons in molecules and atoms. In addition, these achievements provide a foundation for the analysis of the so-called infrared molecular fingerprints by applying infrared spectroscopy to probing the most complex human matter, tissues. This way, the efforts and results of Ferenc Krausz are not only foundational to the field of physics but also provide new avenues in biomedicine and life sciences, some of which are already on the way to being evaluated.

Since 1978, scientists and artists have been honored for "achievements in the interest of humanity and friendly relations between people (...) without regard to nationality, race, color, religion, sex or political views." The Wolf Prizes in physics and chemistry are considered the most prestigious awards after the Nobel Prize. The Wolf Prize is awarded in Israel.

"I am very honored by the award of the Wolf Prize. I consider it a recognition of what I have achieved together with several outstanding colleagues and collaborators, and an appreciation of the future prospects that ultrafast laser research offers for advancing the frontiers of science and technology," says Ferenc Krausz.

Ferenc Krausz shares the award with his colleagues Paul Corkum of the University of Ottawa and Anne L'Huillier of Lund University. Both are also pioneers in the field of attosecond physics.

Pushparani Micheal Raj is “Physicist of the Week” of the German Physical Society (DPG). Since January 2018, the Equal Opportunities Working Group of the DPG has been presenting a female physicist in a short portrait every week.

As CMF’s Microfluidic Scientist in the BIRD research group, Pushpa develops devices to diagnose disease conditions for various types of cancer using Ultra-fast Infra-Red spectroscopy studies in the range of attosecond. Microfluidics is a versatile and robust tool that requires only a few microliters of patients’ biosamples without compromising data accuracy and precision. Pushpa is interested in developing point-of-care diagnostic tools for personalized medicine and preventive medicine, drug discovery, and drug delivery. She aims to contribute to powerful yet affordable tools against lethal diseases like cancer.

The dream that Pushpa wants to chase is a Cancer-Free society!

To support her dreams BIRD and CMF join hands.

For more information see here:

www.dpg-physik.de

Important step for the H4H project as its new website has just launched.

The Center for Molecular Fingerprinting has reached a new milestone as the H4H project’s website has been launched. The website provides detailed information about the research program and also invites people to take part and volunteer. Website visitors can find the list of all the collaborating institutions where they can join and participate in our study.

The H4H (Health for Hungary - Hungary for Health) project is part of a cutting-edge nonprofit research program that aims to develop a personalized infrared laser-based novel diagnostic tool for the future of healthcare.

As an essential part of the research is the participation of healthy individuals voluntarily, it is important that we reach a wide range of people and make them aware of the benefits of the H4H project. We believe that this new platform will help educate potential volunteers and with their participation, the H4H project will move further forward. Thus, it can contribute to the development of medicine, with the possibility of creating a reliable health monitoring system improving the quality of life in the future for all of us.

We invite you to take a look at www.h4h.hu.

On the 11th of January 2022, the inauguration ceremony of the Incubator House in the Szeged Science Park took place. The building, which is located next to the ELI-ALPS Laser Research Centre in the Science Park, has been renovated and is now the headquarters of the Hungarian Molecular Medicine Centre of Excellence. Representatives of the European Molecular Biology Laboratory also attended the inauguration of the incubator. The Center for Molecular Fingerprinting, as a National Laboratory for Life Sciences Research, was represented by Dr. László Sándor Vastag, our Managing Director.

The ceremony included attendees such as Edith Heard, Director General of EMBL, Plamena Markova, Head of International Relations, and Vladimir Benes, Head of the Genomics Core Facility. The EMBL delegation was joined by Prof. Dr. László Palkovics, the Hungarian Minister for Innovation and Technology, Dr. Christoph Sensen, Director General of the HCEMM, and István Szabó Ph.D., Vice President for Science and International Affairs.

Scientific partnerships and knowledge sharing mark the beginning of an exciting period, especially as EMBL will start its new 5-year scientific program on the 1st of January 2022.

Prof. Edith Heard, Director General of the European Molecular Biology Laboratory (EMBL), said: 'The new program has an ambitious goal: to usher in a new era of life sciences in Europe. Achieving a complete understanding from molecules to entire ecosystems. The focus of research is human health. "We hope that the project will also help to address major societal challenges such as climate change, biodiversity loss, and emerging infectious diseases and cancers. The Programme will integrate life sciences research in the Member States and help them achieve a socio-economic green recovery. The scientific challenges we will address - and the major societal issues we will address - cannot be tackled by any country or discipline alone. The aim of this program is for EMBL to engage with its member countries in an unprecedented way over the next 5 years".

EMBL's network provides a unique opportunity to put European expertise in Hungarian life sciences research into practice. HCEMM, as part of the National Laboratories Programme, brings together the best skills and strengths of Hungarian researchers. The new base in Szeged will help the HCEMM become a regional scientific center for cutting-edge molecular medicine, training, and employment of highly qualified researchers.

"The mission of HCEMM is to carry out research and development on Healthy Ageing based on four pillars: cancer research, metabolic diseases, cardiovascular diseases and infectious diseases. The aim is to develop new diagnostic methods and treatment options that will improve quality of life while reducing healthcare costs. The furnishing of the laboratories and offices will also start within days," said Dr. Christoph Sensen, Director General of the HCEMM.

Our research institute has started discussions with the European Molecular Biology Laboratory to identify possible areas of future collaboration.

Viola Zóka has taken a big step. She has moved from Hungary to Garching, near Munich. The biological-technical assistant joined the Hungarian "Center for Molecular Fingerprinting" (CMF) in October 2020. CMF works closely with the attoworld group at the Max Planck Institute of Quantum Optics (MPQ) and the Ludwig Maximilian University of Munich (LMU). In this framework, this institution employs a number of scientists and assistants on the Garching campus for the attoworld team's joint research project Lasers4Life (L4L), in addition to the staff in Budapest.

The L4L researchers have set themselves the goal of using a new ultrashort-pulse laser technology to detect molecules in the blood that can indicate whether an organism is healthy or suffering from cancer.

In our first employee portrait today, we introduce you to Viola Zóka. Here she reports on her exciting work. And she talks about her experiences living in Munich and Germany, a country she is just discovering.

The cmf research team welcomes Dionysios Potamianos. He just finished his Phd work in Prof. Reinhard Kienberger´s group at the Technical University Munich on femtosecond and attosecond electron dynamics of semiconductor systems. He joined our team as a laser engineer with the focus on infrared fingerprinting technology. He will help us develop the next-generation instruments for human blood measurements based on a new ultra-stable diode-pumped Cr:ZnS laser platform.

CMF's goal is to develop new laser-based tools for monitoring human health in a new way, not possible before.

How? By analyzing blood samples in an innovative process using ultrashort laser flashes.

By joining CMF’s group and supporting our research program you can make an important and far-sighted contribution to our population and hopefully you can help to detect severe diseases at an early stage in the future, so that optimal therapy may become possible before the disease can fully develop!

Have a look at our positions and contact Eszter Márton Szűcs on MUK HR Department if you have any other questions!

1. Laboratory Manager
2. Laboratory Associate
3. Head of Laser Laboratory/Senior Laser Scientist
4. Laser Technician

Join us in shaping the future of healthcare!

CMF’s promising molecular fingerprint methodology gets separate chapter in Max Planck Institute of Quantum Optics (MPQ)’s Attoworld image movie, filmed on 19th October 2021.

One of the CMF’s main research partner institution: MPQ’s Attoworld group – led by Prof. Dr. Ferenc Krausz – gives home to explore and exploit electron-light interactions as they occur in real-time. Our vision together is creating a breakthrough in the current health monitoring system and shaping the future of healthcare.

The MPQ image film shooting started with an interview with Prof. Dr. Ferenc Krausz (Scientific Director of CMF), in which he answered questions about the scientific content and application areas of attosecond research and talked about motivations and visions. They captured MPQ lab scientists’ daily work, and in the afternoon, they visited the Biolabs and the Lex laboratories, where the science teams develop the new approach of Infrared Molecular Fingerprinting in cooperation with CMF.

Cancers can grow in numerous places within our bodies and present tremendous threat to our health. But if one could spot cancerous growth early on, the chances to win over it would be higher. Are there ways of achieving this? The team closely collaborating with the Center for Molecular Fingerprinting Research (CMF) from the Laser Physics departments of the Ludwig-Maximilians-University (LMU) in Munich revealed that infrared spectroscopic profiling can be used to pick up molecular traces that solid tumors leave in our bloodstream.

Detecting early and less aggressive cancerous lesions is paramount for having valid medical-treatment options. Besides radiographic tools to visualize tumor tissues within our body, and beyond cutting out tissue biopsies from inner organs for inspection under the microscope, modern diagnostic approaches often focus on non-invasive cancer detection: They analyze bodily fluids and try to capture macroscopically “invisible” molecular changes caused by cancer. In fact, tumors disseminate many aberrant metabolic products and signaling molecules into their surroundings. Likewise, tumors also characteristically interact with adjacent normal cells of a tissue, and later on with our immune cells and blood vessels. These interactions substantially affect the type and amount of many molecules that end up circulating in our bloodstream, even at a time when a tumor is still confined to an organ and not yet metastasizing. However, unambiguously identifying molecules that signify cancer – the holy grail for medical diagnostics and pharma – remains a challenge!

Substantial efforts have been made by the Attoworld research team at the LMU Munich in paving new technological avenues for the most reliable and sensitive detection of molecules in complex liquid matrices. In this context, the BIRD research team (https://www.attoworld.de/bird.html) just published a paper in eLife ( DOI: 10.7554/eLife.68758 ) where they flowed a tiny volume of a blood sample through a cuvette, shined infrared light through it, and quantified the complex changes in the light-wave patterns coming from the blood sample as a function of the identity and number of the hundreds of thousands of different molecules dissolved therein. Extracting information by using machine learning algorithms allows determining a signature that is so highly characteristic of an individual’s blood sample that the signature can be referred to as a “molecular fingerprint”. The BIRD team’s earlier work already showed that such infrared molecular fingerprints were highly reproducible over repeated blood draws from an individual (Huber et al., Nat. Communications 2021, PMCID: PMC7940620).

The size of the problem in tracing disease like cancer by infrared molecular fingerprinting now becomes immediately obvious: One has to move to the population level and explore hundreds of individuals to be in the position to extract the difference between the average healthy fingerprint and the average disease fingerprint. How does it work in real life? In collaboration with medical doctors from LMU clinics, the BIRD team set up a matched case-control clinical study and performed comparative infrared molecular fingerprinting on samples from patients with independently diagnosed lung, prostate, breast, or bladder carcinomas. And indeed, infrared fingerprinting of blood was surprisingly robust and correctly detected the cancer state. Excitingly, infrared fingerprints could be utilized, not only for detecting cancer but also for distinguishing between different cancer types, indicating that each had triggered specific molecular alterations.

Could the approach move into the clinics one day? While still far from being a method that patients can benefit from in medical clinics, the published study substantiates the expectation that, in the future, infrared fingerprinting may become useful for aiding cancer diagnosis or even for cancer screening of low-grade cancers that would go unnoticed using current cancer tests. In particular, infrared fingerprinting may be propelled to yet another level soon. Especially when ultrafast light sources and high-precision electric-field-based metrologies from the Attoworld’s research will come into play.

The path can be seen, and the quest continues.

With their Research Article published in “Angewandte Chemie Int. Ed.”, Liudmila Voronina, Mihaela Žigman et al. made it on the cover of the 2021-60/31 June 2021 issue. The picture shows a snapshot of blood serum composition that reflects the health state of an individual. It can be obtained using infrared spectroscopy in a simple and inexpensive manner, but the molecular nature of the disease-related changes therein remains poorly understood. In their article the researchers report using proteomics to reveal a set of proteins that contribute the most to infrared absorption of blood serum and show that they create a distinct signature of lung cancer. The cover image was designed by the corresponding authors and created by Dennis Luck.

Original publication:
Molecular Origin of Blood-Based Infrared Spectroscopic Fingerprints
L. Voronina, C. Leonardo, J. Mueller-Reif, P. Geyer, M. Huber, M. Trubetskov, K. Kepesidis, J. Behr, M. Mann, F. Krausz, M. Žigman
Angewandte Chemie 60, 17060 (2021)

The “Center for Molecular Fingerprinting” (CMF) in Hungary has achieved another milestone and collected its first blood samples for its future research in health monitoring in the course of the medical study “Health for Hungary” (H4H).

The future of healthcare is at a turning point - modern diagnostic techniques are moving towards a preventive and personalized diagnostic approach, rather than a treatment-after-detection used this far. The overriding aim at CMF is thus to detect severe health conditions and diseases well before symptoms develop - to be able to treat them better. Analysis of the composition of blood samples with ultrashort laser pulses could provide the opportunity for personalised health monitoring by repeated sampling of the same person over time. And this is where “Center for Molecular Fingerprinting“ (CMF) steps in:

July 27th, 2021, marked an important milestone for the research activities of the CMF in Hungary. As part of the "Health4Hungary" (H4H) study, that is aimed to establish infrared fingerprinting for health monitoring, the first blood samples for innovative early detection of diseases were successfully collected for CMF in a first kick-off: The doors for this nation-wide research program just opened at the end of July at the medical cooperation partner “Vita Verum Medical Bt.” (at Székesfehérvár near Budapest), being the initial site in a series of further ones to be joining soon.

After intensive training of the medical staff and coaching regarding the data protection guidelines by the CMF team, the first volunteers were welcomed for blood collection. The H4H took off is the tipping point for the large study to happen across Hungary!

What is this research and study good for? CMF's goal is to develop new laser-based tools for monitoring human health in a new way, not possible before. How? By analyzing blood samples in an innovative process using ultrashort laser flashes. This unique and complex technique has its origin in the attoworld research group of Prof. Ferenc Krausz in Munich. The application of how to use these laser pulses to probe human health was established within the team around Dr. Mihaela Zigman and will be further developed in collaboration with CMF. The goal of the H4H program is to recruit individuals as volunteers from broad segments of the Hungarian population - to facilitate the development of this research and to finally develop a new possibility to track and monitor development of diseases.

The project is planned for several years and aimed at involving 10,000+ individuals at numerous sites across Hungary. The multiple medical centers over the country will not only provide convenient access for anyone wishing to participate. They also ensure that samples are taken from different geographical areas of Hungary to ideally cover a broad spectrum of the Hungarian population.

After data collection and blood sampling, the tubes are pseudonymously transmitted to the research group. In this way, it is not possible for the researchers to personally identify the test person due to data protection regulations. In the next step, the blood samples are stored under special cooling conditions for laser-based data analysis and subsequently evaluated. During the blood donation for research purposes an additional tube is obtained, providing the volunteer with regular lab results, not only blood count but also blood chemistry results.

Furthermore, contributing to this research program will be making an immensely important and far-sighted contribution for our population and our relatives, our children, and our grandchildren, which will hopefully all help to detect severe diseases at an early stage in the future, so that optimal therapy may become possible before the disease can fully develop!

The core technology at CMF for detecting diseases by their molecular fingerprints in a blood sample is field-resolved infrared spectroscopy. It relies on the generation of extremely short infrared pulses by nonlinear laser technology to excite the molecules in the sample, followed by recording the ringing of the molecular response. The sensitivity for disease detection depends on the brightness of the infrared laser pulses and their spectral information content, i.e., on how many different molecular vibrations the infrared pulses can excite simultaneously. Scaling the brightness and spectral content currently requires an ever increasing in complexity and size of the laser systems. In addition, conventional scaling approaches ultimately reach the fundamental limits of the involved conversion processes.

In a collaboration between the CMF, the LMU Munich, and the Max-Planck Institute for Quantum Optics Dr. Shizhen Qu, Dr. Kafai Mak, Dr. Alexander Weigel, and Prof. Ferenc Krausz have now proposed the elegant solution to amplify the infrared pulses with quantum cascade lasers (QCLs). QCLs are compact on-the-chip laser devices, which can reach Watt-scale infrared optical output with direct electrical power supply – much more than typically achievable with nonlinear techniques. The core of the invention is to send the ultrashort infrared pulses into a combination of QCLs to boost them to previously unachievable power levels. Conveniently, the emission characteristics of QCLs can be tailored by their semiconductor layer structure to specifically amplify spectral components that excite characteristic fingerprint signatures in the blood samples. By selectively enhancing only those parts of the pulse that contribute to the disease-specific fingerprint signatures with a combination of QCLs we expect to reach new levels of sensitivity. With appropriate timing, also amplification of the pure molecular fingerprint signal itself is conceivable.

This first joint patent application witnesses the successful collaboration of the three institutions on the way towards highly sensitive blood-based disease detection and health monitoring.

Thousands of researchers are seeking ways to capture human health within a simple probe. Why? Every person is unique – in the personality as well as in terms of health. And the task of defining the healthy state at a populational level is just colossal. In the face of this, it is crucial to detect aberrations in health as soon as only possible, raising the alarm that a disease is sneaking into one’s body. Many diseases could be better coped with if we were alarmed earlier, as they only start developing. Especially cancer. This is where less invasive ways of disease detection come into play.

In a very inter-disciplinary team at the laser physics department of the LMU Munich, we believe to have made a step in this direction: We analyzed a fluid that connects all the organs – blood. The idea is familiar to anyone from medical check-ups, and it has recently been used for profiling with modern omics techniques. In our case, however, we exposed tiny amounts of blood to infrared light and captured the vibrations originating from the soluble biomolecules. In collaborative work with medical doctors from the LMU Comprehensive Pneumology Center, we set up a proof-of-principle clinical study to collect blood of individuals that were definitely known to have lung cancer, and in parallel from generally healthy, comparable individuals. We measured their blood samples with infrared spectroscopy. And finally - with quite high certainty - we succeeded to tell apart whether a person had lung cancer or not. From a mere drop of blood.

Eureka? Well, we want to go even further. While infrared fingerprints may distinguish lung cancer, they do not yet inform us about the individual blood components that make up the difference. Nevertheless, it would be good to know their identity to be able to further improve the method. This is what we demonstrated in a new study just published in Angewandte Chemie (DOI: 10.1002/anie.202103272). It is all about a combination of two techniques that are usually applied separately: mass spectrometry and infrared spectroscopy. The aim was to decode the actual chemical changes behind the previously “black box” infrared fingerprints of lung cancer. Now, with mass spectrometry of blood samples performed at the Max Planck Institute of Biochemistry in Munich, we identified a set of 12 proteins that account for the spectral signature of lung cancer, where early diagnostic markers are currently missing. All of these proteins were known since a long time. Now - like old dogs playing new tricks - the combinatorial protein signature that we defined turns a new page in diagnostic efforts. And this signature can be measured in a matter of minutes using infrared light!

So are we now one step closer to capturing disease and defining health? Certainly so. Especially as laser scientists at our department are engineering new ways of delivering ever shorter and more precise pulses of light for spectroscopic investigations. Metaphorically, this is like a magnifying lens that allows us to inspect the molecular zoo in our blood at once – in a snapshot. Finally, the results are of broader relevance for many disciplines, as one may generalize our findings to detection of other diseases that leave their traces in blood.

Yet, while we are working on new advances in capturing human health by shining light through drops of blood, we are bearing in mind the notion of Isaak Newton: “What we know is a drop, what we don’t know is an ocean.”.

Mihaela Zigman

Original article:
Angew Chem Int Ed Engl
Molecular Origin of Blood-based Infrared Spctroscopic Fingerprints
Liudmila Voronina, Cristina Leonardo, Johannes B Mueller-Reif, Philipp E Geyer, Marinus Huber, Michael Trubetskov, Kosmas V Kepesidis, Jürgen Behr, Matthias Mann, Krausz Ferenc, Mihaela Žigman
PMID: 33881784

DOI: 10.1002 / anie.202103272
https://onlinelibrary.wiley.com/doi/10.1002/anie.202103272
https://onlinelibrary.wiley.com/doi/10.1002/ange.202107126

After a very long pause due to the pandemic, the chance to listen to a lecture and talk to Ferenc Krausz in person took place just on May 28th in Vienna. It was a special occasion. Not only in a city significant for attoscience but also special to the Hungarian-Austrian scientist Ferenc Krausz who worked there over many years. The Austrian Academy of Sciences (OeAW) held its Ceremonial Congress of 2021 with renowned scientists lead by Anton Zeilinger, president of the OeAW, as well as Austrian president Alexander Van der Bellen, welcoming Ferenc Krausz as the keynote speaker.

Anyone that would like to watch the ceremonial presentation, seeing the results of Ferenc Krausz and his team from the CMF, LMU and MPQ, here you get the chance to see the video: https://youtu.be/4dQn4fe33hc

In a wake of this impulsive lecture, the main Austrian broadcasting house (ORF) held an interview with Ferenc Krausz. And right here you have the chance to listen and read on the interview with journalist Robert Czepel and learn about what happened in the cellar laboratory of the TU Vienna about two decades ago: https://science.orf.at/stories/3206849/

A new study carried out by a team of laser physicists, molecular biologists and physicians based at LMU Munich and the Max Planck Institute for Quantum Optics has confirmed the temporal stability of the molecular composition of blood in a population of healthy individuals. The data provide a basis for a new method of monitoring the constituents of blood and detecting alterations that reveal changes in a person’s state of health.

The molecular composition of the blood provides information regarding one’s state of health, and may be compared to an individual fingerprint. In principle, changes in the constituents of blood can serve as early signs of disease. However, before chemical fingerprints can be utilized for diagnostic purposes, the stability of the molecular patterns in healthy persons over time must be firmly established. Researchers under the direction of Dr. Mihaela Žigman, Head of the Broadband Infrared Diagnostics (BIRD) group in the Department of Laser Physics led by Prof. Ferenc Krausz at LMU Munich, in collaboration with Prof. Dr. Nadia Harbeck at the LMU Medical Centre, have now successfully accomplished this task. With the aid of a method known as Fourier-transform infrared spectroscopy (FTIR), the team has shown that the molecular composition of blood samples obtained from a cohort of healthy donors remains stable over a period of several months, and confirmed that each of the resulting spectra could be clearly assigned to an individual person.

Rapid diagnosis of human diseases is a long standing problem in medicine. As diseases often alter the molecular make-up of circulating body fluids, obtaining a snapshot of their molecular composition would be invaluable in detecting a multitude of diseased states, and the types and concentrations of the many molecules found in the bloodstream can provide vital information on a person’s health. The real challenge, however, comes when one tries to determine the exact composition of body fluids, given that the concentrations of informative molecules are often extremely low. The interdisciplinary BIRD team led by Dr. Mihaela Žigman in Prof. Dr. Ferenc Krausz’s department at LMU, in collaboration with Prof. Dr. Nadia Harbeck at the LMU Medical Centre, has now investigated the stability of the chemical make-up of blood samples over days, weeks and even months.
Based on Fourier-transform infrared measurements (FTIR), the researchers analysed the molecular fingerprints of serum and plasma samples obtained from 31 healthy individuals over the clinically relevant period of 6 months. The study demonstrated that the infrared molecular fingerprint of each individual donor in fact remained stable over periods ranging from a few days to weeks and months, and each temporal profile could be readily attributed to the participant concerned.
“This newly revealed temporal stability of blood-based infrared fingerprints provides a basis for future applications of minimally invasive infrared spectroscopy as a reliable method for the future of health monitoring,” says Mihaela Žigman, leader of the research group.
Standard Fourier-transform infrared spectroscopy, which uses conventional light sources, could soon be replaced by chemical analyses based on infrared lasers. Given the much higher intensity of laser light, the latter method should be more sensitive and precise, and should therefore yield more detailed and informative characterizations of the molecular constituents of blood. The physicists in the attoworld team, led by Prof. Ferenc Krausz, are now working on the laser technologies necessary to achieve this aim. Exposure to intense infrared light causes molecules to vibrate and emit light at specific frequencies, which depend on the chemical structures of the molecules within the sample. Analysis of the components of the resulting spectrum of electromagnetic oscillations enables researchers to assign them to the many types of molecules present in body fluids. As Prof. Krausz and colleagues reported last year, the new method allows minuscule amounts of different classes of molecules to be spectroscopically detected (Nature, 2. January 2020; doi 10.1038/s41586-019-1850-7).
“With our lasers, we can already detect electrical signals emitted by excited molecules with very high sensitivity,” Ferenc Krausz explains. “Such precise measurements of alterations in the molecular composition of body fluids, together with knowledge of the stable molecular fingerprint of healthy controls, opens up new analytical opportunities in biology and medicine,” says Marinus Huber, leading author of the study. “Our results reveal that it is possible to obtain informative, blood-based infrared fingerprints efficiently, repeatedly and in a minimally invasive manner. The key, in this case, is that the analysis ought to be sensitive enough and sufficiently broad to cover a wide range of possible molecules (or types of molecules) - to be in position to monitor personal health and detect disorders at an early stage. Practically speaking, following-up a person’s health status regularly might become paramount for timely-detecting relevant deviations. In addition to its uses in the fields of health monitoring and preventive medicine, systems biology shall also benefit from the availability of the approach,” Mihaela Žigman adds.
-Thorsten Naeser

Original Publication:
Huber, M., Kepesidis, K.V., Voronina, L. et al. Stability of person-specific blood-based infrared molecular fingerprints opens up prospects for health monitoring. Nat Commun 12, 1511 (2021).

https://doi.org/10.1038/s41467-021-21668-5
https://www.nature.com/articles/s41467-021-21668-5
Further information is available from:
Dr. Mihaela Žigman
Ludwig-Maximilians-University Munich
Am Coulombwall 1
85748 Garching, Germany.
E-Mail: zigman@mukkozpont.hu.

When it comes to disease detection and health monitoring with field-resolved molecular fingerprinting, turning our vision into reality requires dedicated technological development at the forefront of our scientific research. It starts from the development of new mid-infrared laser sources via advancing sample handling and detection technologies and goes toward finding optimal data acquisition and processing strategies. Over the last couple of months, a new team has formed at CMF with the particular goal to tackle these technical and scientific challenges. In close collaboration, the CMF laser development and technology team in Garching (Germany) is joining forces with LMU laser scientists to combine all technological advances in a one of a kind prototype device for molecular fingerprinting. Once the laser laboratory of CMF will open its gates in Budapest, this instrument will be fundamental to be used in blood sample analysis. Currently, the CMF team headed by Dr. Alexander Weigel is moving frontiers in laser development and solving experimental challenges towards that end.

We would like to wish a warm welcome to a new colleague: Since October 2020, the research group around Dr. Mihaela Žigman has been supported by Viola Zóka, a new medical-technical assistant!

The young Hungarian completed Bachelor of Science in Chemistry. She had developed her passion for chemistry early on and intensified it by her professional experience in a laboratory in Nagykanizsa, Hidrofilt Ltd. Hungary, where she performed analytical chemistry of water samples. When Viola heard about newly developing infrared molecular fingerprinting to analyze way more complex human blood samples that she was used to, she applied for a job at the Center for Molecular Fingerprinting (CMF). CMF is strongly collaborating with the Laser Physics department of the Ludwig Maximilians University (LMU) Munich and prior to having its own laboratories built and established in Hungary, the samples from the clinical studies lead by CMF will be analyzed at the LMU. And Viola made a move from Hungary to Germany to start her new professional life at the Garching Research Center and directly fuel the CMF research goals from there. Together with laser scientist and molecular biologists, Viola will analyze blood samples for their molecular composition using infrared spectroscopy - something that everyone is very much excited about!

CMF’s strategic partner, the Ludwig-Maximilians-University (LMU) in Munich, Germany, just installed an automated biobanking system for sample storage at temperatures below minus 150°C. What is this good for? Under these very low temperatures - so called “cryogenic” conditions in the atmosphere above liquid nitrogen - human samples, such as blood plasma or actually any biological tissues, can be kept for several years, decades without sample deterioration. It assures that valuable human materials collected in frame of clinical studies can be used in long term and thus enables researchers to analyze these with molecular fingerprinting techniques most efficiently. Such an automated cryogenic system is made of large tightly sealed tank that is capable to store up to 60,000 samples. The system is further equipped with a robotic arm that can pick individual tubes automatically, such that the samples are kept and handled well below minus 100 °C at all times.

This installation has a direct impact for the future of the joint CMF-LMU research aims. On the one hand the two institutions will be conducting joint clinical studies. On the other, LMU biobanking system also serves as a test case for the CMF’s envisioned own biorepository, to be established in Budapest.

Thus, CMF is getting familiar with the best way to store most valuable biological materials for the years of research to come!

In cooperation between the Laboratory of Attosecond Physics at the Max Planck Institute of Quantum Optics and the Centre for Advanced Laser Applications of the Ludwig-Maximilians-Universität München, the King Saud University Riad and the Center for Molecular Fingerprinting (Budapest, Hungary), we have developed a molecular spectroscopy technique that overcomes long-standing limitations of traditional techniques, like Fourier-transform infrared spectroscopy, as described in our recent publication. A powerful femtosecond laser delivers 28 million pulses per second, with highly repeatable waveforms, comprising merely a few infrared-electric-field oscillations. Transmitting these pulses through a complex, molecular sample synchronously excites infrared-active vibrations of molecular bonds, each at its own eigenfrequency. The signals emitted by the vibrationally-excited molecules in the wake of the impulsive excitation coherently add up to a ‘molecular fingerprint’ characteristic of the sample’s molecular composition.

In contrast to traditional spectroscopies, where the entire response of the sample to an infrared excitation hits the detector(s), in field-resolved spectroscopy sub-optical-cycle portions of the time-domain fingerprint field are sequentially carved out by means of nonlinear optics. This dramatically reduces any infrared background on the measured signals, including the noise originating from the excitation and thermal background. This conceptional advance results in an unprecedented detection sensitivity and dynamic range.

We have also demonstrated first biological applications that have so far been beyond the reach of infrared vibrational spectroscopies. These applications include first high-signal-to-noise ratio infrared transmission measurements of living biological tissue and fingerprinting of liquid biopsies with sub-µg/ml sensitivity. Thus, field-resolved spectroscopy promises improved molecular sensitivity and molecular coverage for probing complex, real-world biological and medical settings.

Prof. Ferenc Krausz has recieved the honorary membership of the Roland Eötvös Physical Society, Budapest. After receiving the membership the laser physicist of the Ludwig-Maximilians University München and the Max-Planck-Institute of Quantum Optics held an lecture about how attosecond science technologies can in the future contribute to a new way of finding molecules in human biofluids like blood. This may path the way for medical applications to detect diseases by analyzing so called molecular fingerprints with the help of strong laser light pulses.