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1.
Elife ; 102021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34696827

RESUMO

Recent omics analyses of human biofluids provide opportunities to probe selected species of biomolecules for disease diagnostics. Fourier-transform infrared (FTIR) spectroscopy investigates the full repertoire of molecular species within a sample at once. Here, we present a multi-institutional study in which we analysed infrared fingerprints of plasma and serum samples from 1639 individuals with different solid tumours and carefully matched symptomatic and non-symptomatic reference individuals. Focusing on breast, bladder, prostate, and lung cancer, we find that infrared molecular fingerprinting is capable of detecting cancer: training a support vector machine algorithm allowed us to obtain binary classification performance in the range of 0.78-0.89 (area under the receiver operating characteristic curve [AUC]), with a clear correlation between AUC and tumour load. Intriguingly, we find that the spectral signatures differ between different cancer types. This study lays the foundation for high-throughput onco-IR-phenotyping of four common cancers, providing a cost-effective, complementary analytical tool for disease recognition.


Assuntos
Neoplasias da Mama/diagnóstico , Biópsia Líquida/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias da Próstata/diagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Feminino , Humanos , Aprendizado de Máquina , Masculino
2.
Nature ; 577(7788): 52-59, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894146

RESUMO

The proper functioning of living systems and physiological phenotypes depends on molecular composition. Yet simultaneous quantitative detection of a wide variety of molecules remains a challenge1-8. Here we show how broadband optical coherence opens up opportunities for fingerprinting complex molecular ensembles in their natural environment. Vibrationally excited molecules emit a coherent electric field following few-cycle infrared laser excitation9-12, and this field is specific to the sample's molecular composition. Employing electro-optic sampling10,12-15, we directly measure this global molecular fingerprint down to field strengths 107 times weaker than that of the excitation. This enables transillumination of intact living systems with thicknesses of the order of 0.1 millimetres, permitting broadband infrared spectroscopic probing of human cells and plant leaves. In a proof-of-concept analysis of human blood serum, temporal isolation of the infrared electric-field fingerprint from its excitation along with its sampling with attosecond timing precision results in detection sensitivity of submicrograms per millilitre of blood serum and a detectable dynamic range of molecular concentration exceeding 105. This technique promises improved molecular sensitivity and molecular coverage for probing complex, real-world biological and medical settings.


Assuntos
Biomarcadores/sangue , Análise Química do Sangue/métodos , Soro/química , Espectrofotometria Infravermelho , Biomarcadores/química , Análise Química do Sangue/instrumentação , Humanos , Sensibilidade e Especificidade , Água/química
3.
Sci Rep ; 9(1): 16167, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700057

RESUMO

By checking the reproducibility of conventional mid-infrared Fourier spectroscopy of human breath in a small test study (15 individuals), we found that a set of volatile organic compounds (VOC) of the individual breath samples remains reproducible at least for 18 months. This set forms a unique individual's "island of stability" (IOS) in a multidimensional VOC concentration space. The IOS stability can simultaneously be affected by various life effects as well as the onset of a disease. Reflecting the body state, they both should have different characteristics. Namely, they could be distinguished by different temporal profiles: In the case of life effects (beverage intake, physical or mental exercises, smoking etc.), there is a non-monotonic shift of the IOS position with the return to the steady state, whereas a progressing disease corresponds to a monotonic IOS shift. As a first step of proving these dependencies, we studied various life effects with the focus on the strength and characteristic time of the IOS shift. In general, our results support homeostasis on a long time scale of months, allostasis on scales of hours to weeks or until smoke quitting for smokers, as well as resilience in the case of recovery from a disease.


Assuntos
Fumar/metabolismo , Compostos Orgânicos Voláteis/análise , Testes Respiratórios , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Fumantes
4.
J Breath Res ; 12(4): 046003, 2018 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-29984709

RESUMO

Breath analysis has great potential for becoming an important clinical diagnosis method due to its friendly and non-invasive way of sample collection. Hundreds of endogenous trace gases (volatile organic compounds (VOCs)) are present in breath, representing different metabolic processes of the body. They are not only characteristic for a person, their age, sex, habit etc, but also specific to different kinds of diseases. VOCs, related to diseases could serve as biomarkers for clinical diagnostics and disease monitoring. However, due to the large amount of water contained in breath, an identification of specific VOCs is a real challenge. In this work we present a technique of water suppression from breath samples, that enables us to identify several trace gases in breath, e.g., methane, isoprene, acetone, aldehyde, carbon monoxide, etc, using Fourier-transform infrared spectroscopy. In the current state, the technique reduces the water concentration by a factor of 2500. Sample preparation and data acquisition take about 25 min, which is clinically relevant. In this article we demonstrate the working principle of the water reduction technique. Further, with specific examples we demonstrate that water elimination from breath samples does not hamper the concentration of trace gases in breath. Preliminary experiments with real breath also indicate that the concentrations of methane, acetone and isoprene remain the same during the sample preparation.


Assuntos
Testes Respiratórios/métodos , Análise Espectral/métodos , Água/química , Adulto , Idoso , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Temperatura , Pressão de Vapor , Compostos Orgânicos Voláteis/análise
5.
Nature ; 501(7466): 172-3, 2013 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-24025835
6.
Opt Express ; 21(9): 11606-17, 2013 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-23670017

RESUMO

In passive enhancement cavities the achievable power level is limited by mirror damage. Here, we address the design of robust optical resonators with large spot sizes on all mirrors, a measure that promises to mitigate this limitation by decreasing both the intensity and the thermal gradient on the mirror surfaces. We introduce a misalignment sensitivity metric to evaluate the robustness of resonator designs. We identify the standard bow-tie resonator operated close to the inner stability edge as the most robust large-mode cavity and implement this cavity with two spherical mirrors with 600 mm radius of curvature, two plane mirrors and a round trip length of 1.2 m, demonstrating a stable power enhancement of near-infrared laser light by a factor of 2000. Beam radii of 5.7 mm × 2.6 mm (sagittal × tangential 1/e(2) intensity radius) on all mirrors are obtained. We propose a simple all-reflective ellipticity compensation scheme. This will enable a significant increase of the attainable power and intensity levels in enhancement cavities.


Assuntos
Desenho Assistido por Computador , Lentes , Refratometria/instrumentação , Ressonância de Plasmônio de Superfície/instrumentação , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Modelos Teóricos
7.
Opt Lett ; 37(4): 503-5, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22344087

RESUMO

We present the first (to our best knowledge) femtosecond enhancement cavity in the visible wavelength range for ultraviolet frequency comb generation. The cavity is seeded at 518 nm by a frequency-doubled Yb fiber laser and operates at a peak intensity of 1.2×10(13) W/cm(2). High harmonics of up to the ninth order (~57 nm) are generated in an intracavity xenon gas jet. Intracavity high harmonic powers of several milliwatts for the third harmonic order and microwatts for the fifth harmonic order prove the potential of the "green cavity" as an efficient ultraviolet frequency comb source for future spectroscopic experiments. A limiting degradation effect of the cavity mirrors is avoided by operating at a constant oxygen background pressure.

8.
Opt Express ; 19(13): 12108-18, 2011 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-21716447

RESUMO

We present a low-loss VIS/IR-XUV beam splitter, suitable for high-power operation. The spatial separation of the VIS/IR and XUV components of a beam is achieved by the wedged top layer of a dielectric multilayer structure, onto which the beam is impinging under Brewster's angle (for VIS/IR). With a fused silica wedge with an angle of 0.5° we achieve a separation angle of 2.2° and an IR reflectivity of 0.9995. Typical XUV reflectivities amount to 0.1-0.2. The novel element is mechanically robust, exhibiting two major advantages over free-standing Brewster plates: (i) a significant improvement of heat conduction and (ii) easier handling, in particular for high-optical-quality fabrication. The beam splitter could be used as an output coupler for intracavity-generated XUV radiation, promising a boost of the power regime of current MHz-HHG experiments. It is also suited for single-pass experiments and as a beam combiner for pump-probe experiments.


Assuntos
Desenho de Equipamento , Lasers , Óptica e Fotônica/instrumentação , Raios Ultravioleta , Dinâmica não Linear , Dióxido de Silício/química , Temperatura , Raios X
9.
Opt Express ; 19(11): 10232-40, 2011 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-21643281

RESUMO

We report an efficient intracavity XUV output coupler based on an anti-reflection-coated grazing incidence plate (GIP). Conceptually, GIP is an extension of a Brewster plate, affording low loss of the circulating fundamental light and serving as a highly efficient, extremely broadband output coupler for XUV. Due to the grazing incidence geometry, the short wavelength reflectivity can be extended to the keV range. The first GIP realized shows parameters close to the design. We discuss both the limitations of the GIP in comparison with other XUV output couplers and the applicability of the GIP extension at longer wavelengths, down to the MIR.

10.
Opt Express ; 19(3): 1954-62, 2011 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-21369011

RESUMO

We designed, fabricated and characterized a nano-periodical highly-efficient blazed grating for extreme-ultraviolet (XUV) radiation. The grating was optimized by the rigorous coupled-wave analysis method (RCWA) and milled into the top layer of a highly-reflective mirror for IR light. The XUV diffraction efficiency was determined to be around 20% in the range from 35.5 to 79.2 nm. The effects of the nanograting on the reflectivity of the IR light and non-linear effects introduced by the nanograting have been measured and are discussed.


Assuntos
Nanotecnologia/instrumentação , Refratometria/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Raios Ultravioleta
11.
Opt Express ; 18(25): 26184-95, 2010 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-21164968

RESUMO

We apply spatially and spectrally resolved interferometry to measure the complex ratio between the field circulating inside a high-finesse femtosecond enhancement cavity and the seeding field. Our simple and highly sensitive method enables the measurement of single-round-trip group delay dispersion of a fully loaded cavity at resonance for the first time. Group delay dispersion can be determined with a reproducibility better than 1 fs2 allowing the investigation of nonlinear processes triggered by the high intracavity power. The required data acquisition time is less than 1 s.


Assuntos
Interferometria/instrumentação , Dispositivos Ópticos , Transdutores , Desenho de Equipamento , Análise de Falha de Equipamento/instrumentação
12.
Opt Lett ; 35(12): 2052-4, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20548383

RESUMO

A passive optical resonator is used to enhance the power of a pulsed 78 MHz repetition rate Yb laser providing 200 fs pulses. We find limitations relating to the achievable time-averaged and peak power, which we distinguish by varying the duration of the input pulses. An intracavity average power of 18 kW is generated with close to Fourier-limited pulses of 10 W average power. Beyond this power level, intensity-related effects lead to resonator instabilities, which can be removed by chirping the seed laser pulses. By extending the pulse duration in this way to 2 ps, we could obtain 72 kW of intracavity circulating power with 50 W of input power.

13.
Phys Rev Lett ; 102(21): 213001, 2009 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-19519100

RESUMO

We experimentally demonstrate ultrafast electron diffraction from transiently aligned molecules in the absence of external (aligning) fields. A sample of aligned molecules is generated through photodissociation with femtosecond laser pulses, and the diffraction pattern is captured by probing the sample with picosecond electron pulses shortly after dissociation-before molecular rotation causes the alignment to vanish. In our experiments the alignment decays with a time constant of 2.6+/-1.2 ps.

14.
Phys Rev E Stat Nonlin Soft Matter Phys ; 70(3 Pt 2): 036409, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15524648

RESUMO

Interaction of ultrashort high-intensity laser pulses with solid targets generates relativistic electrons which escape from the target. The kinetics of these ultrashort electron pulses is governed by self-fields generated by the charge of the electron cloud. In this paper an analytical theory is developed which allows calculation of electron trajectories, electron fluxes, and electron spectra at any distance from the target. The theory is exact for two limiting cases: (a) a monoenergetic electron pulse with an arbitrary temporal shape; (b) an infinitely short electron pulse with an arbitrary energy spectrum. These results have applications in high-intensity irradiation experiments, e.g., in experiments irradiating samples with ultrashort electron or x-ray pulses, in developing optics for fourth-generation light sources, and in work relating to x-ray lasers.

15.
Phys Rev E Stat Nonlin Soft Matter Phys ; 69(6 Pt 2): 066404, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15244742

RESUMO

We present measurements of electron densities of plasmas with femtosecond (fs) temporal resolution. The plasmas are generated by laser pulses with different intensities at different time delays. Such plasmas are of great interest as preplasmas for transient, collisionally excited x-ray lasers. The laser pulses producing the plasmas are generated by stretching part of a 130-fs laser pulse of the ATLAS titanium-sapphire laser of our institute and focusing this radiation to a line on molybdenum and silver slab targets. The electron density is measured as a function of distance from the target by interferometry using a Wollaston prism. Using an ultrashort probe pulse allows one to obtain data extremely close, about 10 microm, to the target surface. Experimental data are compared with simulations using the MULTI hydrocode. The results allow comparison of the ablation from a hard (Mo) and a soft (Ag) material, optimization of prepulse-main pulse delay times, and selection of the best pump geometry allowing for propagation of the pump and x-ray beams. These points are key elements for the development of a high-repetition-rate soft-x-ray laser.

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