Wave Mixing Spectroscopy Research Articles

Ultrasensitive Detection and Separation of Pancreatic Cancer Biomarker CA 19-9 Using a Multiphoton Laser Wave-Mixing Detector Interfaced to Capillary Electrophoresis.

The carbohydrate antigen 19-9 (CA 19-9) is the most commonly used biomarker in the clinical diagnosis of pancreatic cancer. Multiphoton nonlinear laser wave-mixing spectroscopy is presented as an ultrasensitive detection method for CA 19-9. Wave mixing is an optical absorption-based method, and hence, one can detect CA 19-9 without labels in their native form using compact ultraviolet (UV) lasers or labeled samples using a visible laser. The wave-mixing signal exhibits a quadratic dependence on the sample concentration, and hence, it is an ideal sensor to monitor small changes in the sample. Wave mixing has inherent advantages over other absorption-based detection methods, including short optical path length (micrometer-thin samples instead of 1 cm cuvette) and excellent spatial resolution (micrometer probe). Since the laser wave-mixing probe volume is small (picoliter), it is convenient to interface to microfluidics or capillary-based electrophoresis systems to enhance chemical specificity. Our wave-mixing detectors could be configured as portable battery-powered devices suitable for field use. Laser wave-mixing spectroscopy offers enhanced selectivity levels for protein detection when coupled with capillary electrophoresis (CE). We report a concentration detection limit of 0.16 U/mL, and a corresponding mass detection limit of 1.2 × 10-8 U, and these detection limits are better than those of chemiluminescence- or ELISA- based methods.

Measuring autoionization decay lifetimes of optically forbidden inner valence excited states in neon atoms with attosecond noncollinear four-wave-mixing spectroscopy

Attosecond noncollinear four wave mixing spectroscopy with one attosecond extreme ultraviolet (XUV) pulse and two few-cycle near-infrared (NIR) pulses was used to measure the autoionization decay lifetimes of inner valence electronic excitations in neon atoms. After a 43-48 eV XUV photon excites a 2s electron into the 2s2p6[np] Rydberg series, broadband NIR pulses couple the 2s2p6[3p] XUV-bright state to neighboring 2s2p6[3s] and 2s2p6[3d] XUV-dark states. Controllable delays of one or both NIR pulses with respect to the attosecond XUV pulse reveal the temporal evolution of either the dark or bright states, respectively. Experimental lifetimes for the 3s, 3p, and 3d states are measured to be 7 +/- 2 fs, 48 +/- 8 fs, and 427 +/- 40 fs, respectively, with 95% confidence. Accompanying calculations with two independent ab initio theoretical methods, NewStock and ASTRA, verify the findings. The results support the expected trend that the autoionization lifetime should be longer for states that have a smaller penetration in the radial region of the 2s core hole, which in this case is for the higher angular momentum Rydberg orbitals. The underlying theory thus links the lifetime results to electron correlation and provides an assessment of the direct and exchange terms in the autoionization process.

Decaying and revival dynamics of molecules revealed by attosecond wave-mixing spectroscopy.

We theoretically investigate the decaying dynamics in model molecules by using attosecond wave-mixing spectroscopy. We find that transient wave-mixing signal in molecular systems can be used to measure the lifetimes of vibrational states with attosecond time resolution. Typically, there are many vibrational states in the molecular system, and the molecular wave-mixing signal with a specific energy at a specific emitting angle is contributed by many possible wave-mixing pathways. In addition, the vibrational revival phenomenon in the previous ion detection experiments has also been observed in this all-optical approach. This work provides a new, to the best of our knowledge, route for the decaying dynamics detection and wave packet control of molecular systems.

Sensitive detection of heart-failure biomarkers natriuretic peptides using multi-photon laser wave-mixing spectroscopy

Nonlinear laser wave-mixing spectroscopy is demonstrated as a fast and sensitive detection method for heart-failure biomarkers, pro-atrial natriuretic peptide (proANP) and brain natriuretic peptide (BNP). Wave mixing is an ultrasensitive optical absorption-based method and analytes can be detected in their native form or labeled with fluorophore and chromophore labels. In this study, we utilized Chromeo P540 dye to label the peptides for wave-mixing detection. The wave-mixing signal is created from the diffraction of incoming photons by the thermal grating at the capillary analyte cell. The signal beam is strong, collimated, and coherent (laser-like) and it is collected using a simple photodetector with an excellent signal-to-noise ratio. We demonstrated advantages of this technique over conventional assays including shorter analysis times, smaller sample requirements, and higher throughput. To enhance detection selectivity and sensitivity levels, wave mixing is effectively coupled to capillary zone electrophoresis (CZE) and field-amplified sample stacking (FASS) methods. We determined detection limits of 7.4 × 10−10 M or 55 zmol and 6.8 × 10−10 M or 51 zmol for proANP and BNP, respectively, and separated and detected both peptides within 2 min. Due to the challenges in the confirmatory diagnoses of heart failure, wave-mixing serves as a potentially beneficial screening tool in addition to the commonly used echocardiographic tests.

Solid state core-exciton dynamics in NaCl observed by tabletop attosecond four-wave mixing spectroscopy

Nonlinear wave mixing in solids with ultrafast x-rays can provide insight into complex electronic dynamics of materials. Here, tabletop-based attosecond noncollinear four-wave mixing (FWM) spectroscopy using one extreme ultraviolet (XUV) pulse from high harmonic generation and two separately timed few-cycle near-infrared (NIR) pulses characterizes the dynamics of the ${\mathrm{Na}}^{+}$ ${L}_{2,3}$ edge core-excitons in NaCl around 33.5 eV. An inhomogeneous distribution of core-excitons underlying the well-known doublet absorption of the ${\mathrm{Na}}^{+}$ $\mathrm{\ensuremath{\Gamma}}$ point core-exciton spectrum is deconvoluted by the resonance-enhanced nonlinear wave mixing spectroscopy. In addition, other dark excitonic states that are coupled to the XUV-allowed levels by the NIR pulses are characterized spectrally and temporally. Approximately $<10\phantom{\rule{0.16em}{0ex}}\mathrm{fs}$ coherence lifetimes of the core-exciton states are observed. The core-excitonic properties are discussed in the context of strong electron-hole exchange interactions, electron-electron correlation, and electron-phonon broadening. This investigation successfully indicates that tabletop attosecond FWM spectroscopies represent a viable technique for time-resolved solid state measurements.

Method for high precision measurement of decaying dynamics using attosecond wave-mixing spectroscopy.

Ultrafast wave-mixing spectroscopies involving extreme ultraviolet (EUV) attosecond pulses provide unprecedented insight into electronic dynamics. Here, we proposed a versatile lifetime-detection method for doubly excited states with odd or even parities by mixing an attosecond EUV pulse with two few-cycle near infrared (NIR) pulses in atomic helium under a noncollinear geometry. By properly choosing the time order of the pulse sequence, the spatially resolved nonlinear signals carry significant information of the decaying dynamics of excited states, which can be utilized to retrieve the lifetimes of states with different parities in a single measurement. The validity and robustness of the method has been verified by numerical simulations based on a few-level model of helium including the spatial distribution of atoms. The accuracy of the lifetime measurement method is better than a few hundred attoseconds. It provides a powerful tool for probing decaying dynamics of the electronic wave packet with superb resolution.

Coupled nuclear-electronic decay dynamics of O2 inner valence excited states revealed by attosecond XUV wave-mixing spectroscopy.

Multiple Rydberg series converging to the O2+c4Σ-u state, accessed by 20-25 eV extreme ultraviolet (XUV) light, serve as important model systems for the competition between nuclear dissociation and electronic autoionization. The dynamics of the lowest member of these series, the 3sσg state around 21 eV, has been challenging to study owing to its ultra-short lifetime (<10 fs). Here, we apply transient wave-mixing spectroscopy with an attosecond XUV pulse to investigate the decay dynamics of this electronic state. Lifetimes of 5.8 ± 0.5 fs and 4.5 ± 0.7 fs at 95% confidence intervals are obtained for v = 0 and v = 1 vibrational levels of the 3s Rydberg state, respectively. A theoretical treatment of predissociation and electronic autoionization finds that these lifetimes are dominated by electronic autoionization. The strong dependence of the electronic autoionization rate on the internuclear distance because of two ionic decay channels that cross the 3s Rydberg state results in the different lifetimes of the two vibrational levels. The calculated lifetimes are highly sensitive to the location of the 3s potential with respect to the decay channels; by slight adjustment of the location, values of 6.2 and 5.0 fs are obtained computationally for the v = 0 and v = 1 levels, respectively, in good agreement with experiment. Overall, an intriguing picture of the coupled nuclear-electronic dynamics is revealed by attosecond XUV wave-mixing spectroscopy, indicating that the decay dynamics are not a simple competition between isolated autoionization and predissociation processes.

Self-heterodyned detection of dressed state coherences in helium by noncollinear extreme ultraviolet wave mixing with attosecond pulses

Noncollinear wave-mixing spectroscopies with attosecond extreme ultraviolet (XUV) pulses provide unprecedented insight into electronic dynamics. In infrared and visible regimes, heterodyne detection techniques utilize a reference field to amplify wave-mixing signals while simultaneously allowing for phase-sensitive measurements. Here, we implement a self-heterodyned detection scheme in noncollinear wave-mixing measurements with a short attosecond XUV pulse train and two few-cycle near infrared (NIR) pulses. The initial spatiotemporally overlapped XUV and NIR pulses generate a coherence of both odd (1snp) and even (1sns and 1snd) parity states within gaseous helium. A variably delayed noncollinear NIR pulse generates angularly-dependent four-wave mixing signals that report on the evolution of this coherence. The diffuse angular structure of the XUV harmonics underlying these emission signals is used as a reference field for heterodyne detection, leading to cycle oscillations in the transient wave-mixing spectra. With this detection scheme, wave-mixing signals emitting from at least eight distinct light-induced, or dressed, states can be observed, in contrast to only one light induced state identified in a similar homodyne wave-mixing measurement. In conjunction with the self-heterodyned detection scheme, the noncollinear geometry permits the conclusive identification and angular separation of distinct wave-mixing pathways, reducing the complexity of transient spectra. These results demonstrate that the application of heterodyne detection schemes can provide signal amplification and phase-sensitivity, while maintaining the versatility and selectivity of noncollinear attosecond XUV wave-mixing spectroscopies. These techniques will be important tools in the study of ultrafast dynamics within complex chemical systems in the XUV regime.

Autoionization dynamics of (2P1/2)ns/d states in krypton probed by noncollinear wave mixing with attosecond extreme ultraviolet and few-cycle near infrared pulses.

The autoionization dynamics of the (2P1/2)ns/d Rydberg states in krypton are investigated using spatially isolated wave-mixing signals generated with a short train of subfemtosecond extreme ultraviolet (XUV) pulses and noncollinear, few-cycle near infrared pulses. Despite ubiquitous quantum beat oscillations from XUV-induced coherences within the excited-state manifold, these wave-mixing spectra allow for the simultaneous evaluation of autoionization lifetimes from a series of Rydberg states above the first ionization potential. Experimentally measured lifetimes of 22 ± 8 fs, 33 ± 6 fs, and 49 ± 6 fs for the wave-mixing signals emitting from the (2P1/2)6d/8s, (2P1/2)7d/9s, and (2P1/2)8d/10s resonances compare favorably with lifetimes for the (2P1/2)6d, 7d, and 8d Rydberg states determined from spectral linewidths. Analysis of the quantum beats reveals that the enhancement of wave-mixing pathways that couple the (2P1/2)nd states to themselves leads to individual reporter state-dependent decays in the wave-mixing signals. The results demonstrate the promise of wave-mixing spectroscopies with subfemtosecond XUV pulses to provide valuable insights into processes governed by electronic dynamics.

Conducting Excitation and Emission Spectra in the IR Regime: Frequency-Domain Time-Resolved Vibrational Four Wave Mixing Spectroscopy.

We report new features of recently developed ultrafast coherent multidimensional spectroscopy (CMDS), an optical analogue to multidimensional NMR. By using both frequency- and time-domain nonlinear four wave mixing methods, CMDS is able to directly observe coherence transfer (CT), the coherent quantum mechanical analogue of population relaxation. Using a mixture of acetonitrile and magnesium perchlorate (1.0 M) as a model system, we demonstrated that this one color- and population-involving CT process makes CMDS capable of measuring samples with features that mimic excitation and emission spectral measurements in fluorescence spectroscopy. With the new capabilities, one might develop CMDS into a versatile vibrational tool for revealing the role of coherence as a design element in realizing a function. Furthermore, CT-based vibrational resonance energy transfer (VRET) methods may be developed for label-free biosensing and imaging, such as those demonstrated by fluorescence resonance energy transfer (FRET).

Excited-state vibronic wave-packet dynamics in H2 probed by XUV transient four-wave mixing

Author(s): Cao, W; Warrick, ER; Fidler, A; Leone, SR; Neumark, DM | Abstract: The complex behavior of a molecular wave packet initiated by an extreme ultraviolet (XUV) pulse is investigated with noncollinear wave mixing spectroscopy. A broadband XUV pulse spanning 12-16 eV launches a wave packet in H2 comprising a coherent superposition of multiple electronic and vibrational levels. The molecular wave packet evolves freely until a delayed few-cycle optical laser pulse arrives to induce nonlinear signals in the XUV via four-wave mixing (FWM). The angularly resolved FWM signals encode rich energy exchange processes between the optical laser field and the XUV-excited molecule. The noncollinear geometry enables spatial separation of ladder and V- or Λ-type transitions induced by the optical field. Ladder transitions, in which the energy exchange with the optical field is around 3 eV, appear off axis from the incident XUV beam. Each vibrationally revolved FWM line probes a different part of the wave packet in energy, serving as a promising tool for energetic tomography of molecular wave packets. V- or Λ-type transitions, in which the energy exchange is well under 1 eV, result in on-axis nonlinear signals. The first-order versus third-order interference of the on-axis signal serves as a mapping tool of the energy flow pathways. Intra- and interelectronic potential energy curve transitions are decisively identified. The current study opens possibilities for accessing complete dynamic information in XUV-excited complex systems.

Sensitive detection of malachite green and crystal violet by nonlinear laser wave mixing and capillary electrophoresis.

An ultrasensitive label-free antibody-free detection method for malachite green and crystal violet is presented using nonlinear laser wave-mixing spectroscopy and capillary zone electrophoresis. Wave-mixing spectroscopy provides a sensitive absorption-based detection method for trace analytes. This is accomplished by forming dynamic gratings within a sample cell, which diffracts light to create a coherent laser-like signal beam with high optical efficiency and high signal-to-noise ratio. A cubic dependence on laser power and square dependence on analyte concentration make wave mixing sensitive enough to detect molecules in their native form without the use of fluorescent labels for signal enhancement. A 532 nm laser and a 635 nm laser were used for malachite green and crystal violet sample excitation. The use of two lasers of different wavelengths allows the method to simultaneously detect both analytes. Selectivity is obtained through the capillary zone electrophoresis separation, which results in characteristic migration times. Measurement in capillary zone electrophoresis resulted in a limit of detection of 6.9 × 10(-10)M (2.5 × 10(-19) mol) for crystal violet and 8.3 × 10(-11)M (3.0 × 10(-20) mol) for malachite green at S/N of 2.

Sensitive analysis of α-synuclein by nonlinear laser wave mixing coupled with capillary electrophoresis

Multi-photon nonlinear laser wave-mixing spectroscopy is a novel absorption-based technique that offers excellent detection sensitivity for biomedical applications, including early diagnosis and investigation of neurodegenerative diseases. α-Synuclein is linked to Parkinson's disease (PD), and characterization of its oligomers and quantification of the protein may contribute to understanding PD. The laser wave-mixing signal has a quadratic dependence on analyte concentration, and hence the technique is effective in monitoring small changes in concentration within biofluids. A wide variety of labels can be employed for laser wave-mixing detection due to its ability to detect both chromophores and fluorophores. In this investigation, two fluorophores and a chromophore are studied and used as labels for the detection of α-synuclein. Wave-mixing detection limits of PD-related protein conjugated with fluorescein isothiocyanate, QSY 35 acetic acid, succinimidyl ester, and Chromeo P503 were determined to be 1.4 × 10−13 M, 1.4 × 10−10 M, and 1.9 × 10−13 M, respectively. Based on the laser probe volume used, the corresponding mass detection limits were determined to be 1.1 × 10−23 mol, 1.1 × 10−20 mol, and 1.5 × 10−23 mol. This study also presents molecular-based separation and quantification of α-synuclein by laser wave mixing coupled with capillary electrophoresis.

Second Hyperpolarizability of C–H, C–D, and C≡N Stretch Vibrations Determined from Computational Raman Activities and a Comparison with Experiments

We have recently demonstrated that the second hyperpolarizability γ of a selected vibrational mode of a molecule can be determined by using the computational Raman activity against an internal standard with a known Raman γ value. This approach provides a convenient way for prediction of the γ magnitude of DOVE four wave mixing spectroscopy, an optical analogue to two-dimensional (2D) NMR. Here, by using the Hartree-Fock (HF) method, the density functional theory (DFT) method, and the second-order Møller-Plesset perturbation theory (MP2) method, we extend our early work from the less anharmonic region <2000 cm(-1) into the more anharmonic region >2000 cm(-1) covering C-H, C-D, and C≡N stretching modes of benzene, deuterated benzene, acetonitrile, deuterated acetonitrile, and tetrahydrofuran. The computed Raman γ values of these vibrational modes have been determined by using either the 992 cm(-1) Raman band of benzene or the compound's own Raman band (C-C stretch) around 800-1000 cm(-1) as an internal standard. In this more anharmonic region, the HF method with a larger basis set provides the best outputs and the predicted Raman γ values agree well with experimental values for most of the vibrational modes studied. By choosing a suitable method and basis set, this facile approach could be applied to a broader spectral range for Raman γ estimation of various materials.

Multistep Quantum Master Equation Theory for Response Functions in Four Wave Mixing Electronic Spectroscopy of Multichromophoric Macromolecules

This work provides an alternative derivation of third order response functions in four wave mixing spectroscopy of multichromophoric macromolecular systems considering only single exciton states. For the case of harmonic oscillator bath linearly and diagonally coupled to exciton states, closed form expressions showing all the explicit time dependences are derived. These expressions can provide more solid physical basis for understanding 2-dimensional electronic spectroscopy signals. For more general cases of system-bath coupling, the quantum master equation (QME) approach is employed for the derivation of multistep time evolution equations for Green function-like operators. Solution of these equations is feasible at the level of 2nd order non-Markovian QME, and the new approach can account for inter-exciton coupling, dephasing, relaxation, and non-Markovian effects in a consistent manner.

Ultrafast acquirement of combined time and frequency spectroscopic data

The incorporation of spectral resolution in time resolved Four Wave Mixing spectroscopy provides important information for the interpretation of the observed spectra. We demonstrate experimentally a new method whereby the combined time and frequency resolved information may be obtained within a single laser pulse. The method is based on Phase Matching Spectral Filtering for the tuning of the generated nonlinear signal, which in turn utilizes the constraints imposed by strict phase matching of parallel input beams in our geometrical arrangement. The measurements were performed on a simple molecule (CH 2Br 2), and are used for identification of molecular degrees of freedom not otherwise possible in pure time resolved methods.

Optical N-Wave-Mixing Spectroscopy with Strong and Temporally Well-Separated Pulses: The Doorway−Window Representation

We have extended the doorway-window representation of optical pump-probe spectroscopy with weak pulses toward N-wave-mixing spectroscopy with temporally well-separated pulses of arbitrary strength. The expressions for the signals in the strong-pulse doorway-window representation are derived in the framework of the nonperturbative theory of N-wave-mixing spectroscopy. The strong-pulse doorway-window representation is complementary to the equation-of-motion phase-matching approach. The latter fully accounts for pulse-overlap effects in signals induced by weak pulses but is computationally more expensive. The performance of the doorway-window approximation for temporally well-separated strong pulses is illustrated for an electronic two-level system with an underdamped Condon-active vibrational mode.

Nonlinear optical response of hole–trion systems in quantum dots in tilted magnetic fields

AbstractWe discuss, from a theoretical point of view, the four wave mixing spectroscopy on an ensemble of p‐doped quantum dots in a magnetic field slightly tilted from the in‐plane configuration. We describe the system evolution in the density matrix formalism. In the limit of coherent ultrafast optical driving, we obtain analytical formulas for the single system dynamics and for the response of an inhomogeneously broadened ensemble.The results are compared to the previously studied time‐resolved Kerr rotation spectroscopy on the same system. We show that the Kerr rotation and four wave mixing spectra yield complementary information on the spin dynamics (precession and damping). (© 2011 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)

Four Wave Mixing spectroscopy at the interface between the time and frequency domains

We demonstrate a new approach to Four Wave Mixing spectroscopy involving simultaneous measurements at time and frequency domains, where spectral selectivity is achieved by phase matching filtering, and the time resolution is obtained within a single ultra-short pulse. We analyze the Four Wave Mixing signal, and show that our method is capable for discrimination between different spectroscopic pathways of vibrational coherences modulating the scattered signal.

Fully and Partially Coherent Pathways in Multiply Enhanced Odd-Order Wave-Mixing Spectroscopy

Nuclear magnetic resonance spectroscopy relies on using multiple excitation pulses to create multiple quantum coherences that provide great specificity for chemical measurements. Coherent multidimensional spectroscopy (CMDS) is the optical analogue of NMR. Current CMDS methods use three excitation pulses and phase matching to create zero, single, and double quantum coherences. In order to create higher order multiple quantum coherences, the number of interactions must be increased by raising the excitation intensities high enough to create Rabi frequencies that are comparable to the dephasing rates of vibrational coherences. The higher Rabi frequencies create multiple, odd-order coherence pathways. The coherence pathways that involve intermediate populations are partially coherent and are sensitive to population relaxation effects. Pathways that are fully coherent involve only coherences and measure the direct coupling between excited quantum states. The fully coherent pathways are related to the multiple quantum coherences created in multiple pulse NMR methods such as heteronuclear multiple quantum coherence (HMQC) spectroscopy with the important difference that HMQC NMR methods have a defined number of interactions and avoid dynamic Stark effects whereas the multiply enhanced odd-order wave-mixing pathways do not. The difference arises because CMDS methods use phase matching to define the interactions and at high intensities, multiple pathways obey the same phase matching conditions. The multiple pathways correspond to the pathways created by dynamic Stark effects. This paper uses rhodium dicarbonyl chelate (RDC) as a model to demonstrate the characteristics of multiply enhanced odd-order wave-mixing (MEOW) methods. Dynamic Stark effects excite vibrational ladders on the symmetric and asymmetric CO stretch modes and create a series of multiple quantum coherences and populations using partially and fully coherent pathways. Vibrational quantum states up to v = 6 are excited. A series of spectra provides different two-dimensional cross sections through the multidimensional parameter space involving two excitation frequencies, the frequency of the output coherence, and the excitation pulse time delays. The spectra allow the identification of 18 different overtone and combination band states. Comparison with a local mode model with two anharmonic Morse oscillators with interbond coupling shows excellent agreement.