Center for Molecular Fingerprinting laser science division

Research group of Dr. Alexander Weigel

 

The response of a complex sample like human blood serum to infrared irradiation carries detailed information on its molecular composition. Our vision is to use this technology to identify the minuscule infrared fingerprints that accompany developing diseases like cancer, so that in future a regular, standardized infrared blood analysis can give first indication of severe diseases in their earliest state. On our way to this goal, our team combines ultrafast laser technology and field-resolved metrology and develops unique instruments that break the current limitations of infrared spectroscopy and reach new levels of sensitivity and specificity in infrared-based disease detection.

Our infrared fingerprinting instruments excite the human blood sample with an ultra-broadband, few-cycle mid-infrared pulse, and record the electric field response emitted by the sample with electro-optic sampling (see below). The field-resolved detection provides not only a direct view on the physical processes of light-matter interaction, but also allows to isolate the pure infrared fingerprint response of a sample and reach unprecedented detection sensitivity. Our research brings together new ultra-broadband, low-noise infrared laser sources with high-speed, high-dynamic-range field-resolved detection, and explores engineering solutions to reach the long-term stability and reproducibility needed for large-scale human blood sample studies.

 

Figure 1: Field-resolved infrared fingerprinting for disease detection and human health monitoring. Graphic: Dennis Luck

directly-diode-pumped Cr-doped II–VI lasers: new ultra-low-noise laser frontends

Lasers with Cr-doped II-VI gain media (Cr:ZnS, Cr:ZnSe) have evolved recently as new sources for ultrashort few-cycle pulses with wavelengths around 2-3 um. This wavelength range has proven highly favorable for the efficient generation of infrared pulses with broad spectral bandwidth. In order to reach extremely quiet and low-noise laser performance, we directly pump our Cr-doped oscillators with laser diodes, drawing on the advances, for example, in the telecommunication sector. Nonlinear pulse compression and dispersion management with advanced multi-layer optics allow us to produce ultra-stable few-cycle pulses as the basis for the instrument. Our laser and mechanical engineers work together to implement these technologies into long-term stable laser systems that provide the highly reproducible performance needed for investigating and comparing the blood of patients over many years.

 

diode-pumped Cr-doped II-VI amplifiers: more power at lowest noise

In addition to our laser oscillators, we develop amplifiers based on Cr-doped gain media to boost the power to the multi-Watt level. Also in this case, we employ direct diode pumping technology to maintain our the excellent noise performance of our laser sources with amplification.

 

CEP stabilization and repetition-rate synchronization: controlling the laser pulse trains

Not only the stability of the output power, but also the reproducibility of the emitted few-cycle waveforms and the exact timing, with which the pulses are emitted, are important for applying ultrafast lasers in field-resolved infrared fingerprinting. Therefore, we work on actively stabilizing these parameters to highest achievable levels. In order to exactly reproduce the waveforms of the emitted pulses we develop ultra-low noise carrier envelope phase (CEP) stabilization for our Cr-doped lasers. Here we benefit from the intrinsic stability of the diode-pumped lasers themselves. By synchronizing two lasers in their repetition rate, we are further able to control the exact timing with which pulses from the lasers are arriving at our field-resolved detection. This is the prerequisite for ultra-rapid scanning techniques using two laser oscillators.

ultra-broadband infrared generation and high-dynamic-range field-resolved detection

Building on the experience of the attoworld we use nonlinear intra-pulse difference frequency conversion to generate stable infrared waveforms that can cover the plethora of mid-infrared vibrational resonances of biological samples. After sending these pulses through the sample we record the electric fields of excitation pulse and sample response with high-dynamic-range electro-optic sampling. We are constantly working on schemes to simultaneously advance the spectral coverage of the mid-infrared pulses and the detection sensitivity. We also explore techniques to guarantee long-term reproducibility of the measured infrared fingerprints.

freezing the noise with ultra-rapid scanning

Even lowest-noise laser sources exhibit fluctuations and drifts in their output parameters with prominent contributions, for example, from mechanical motion and electric noise at sub-kHz frequencies. Recording a measurement of the electric-field oscillations of the mid-infrared pulses with electro-optic sampling requires an optical delay scan. Typically, such a measurement is realized by moving a mechanical stage, limiting the acquisition speed to around 1 trace per second, so that laser noise distorts the individual scans. Scanning instead the optical delay at multiple kHz, records measurements faster than most of the laser fluctuations, and thereby  freezes  the laser parameters during a single scan. Therefore, we combine in our next-generation infrared fingerprinting systems ultra rapid scanning approaches with electro-optic sampling detection. One of the most versatile ultra-rapid scanning techniques builds on the frequency synchronization of two separate lasers. We are working on methods to calibrate the delay axis of the individual scans with attosecond precision and develop algorithms to handle the enormous amounts of data produced during such measurements, ideally in real time. As shown (see below), we are able with this technique to record thousands of traces per second and average them directly in time domain, without any signal distortion.

 

Figure 5: Infrared waveform recorded with ultra-rapid scanning, over an acquisition time of 230 s. Precise calibration of the individual delay axes allows to average 650,000 traces, directly in time domain.

  • ultra-stable dual-oscillator lock
  • CEP stabilization with 9 mrad phase noise (World Record!)

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