Frequency Modulation Spectroscopy Research Articles

A study on the corrosion inhibition impact of newly synthesized quinazoline derivatives on mild steel in 1.0 M HCl: Experimental, surface morphological (SEM-EDS and FTIR) and computational analysis

Two new quinazoline derivatives were investigated in this research, namely 12-(4-methoxyphenyl) and 3,3-dimethyl-12-(4-nitrophenyl)-3,4,5,12-tetrahydrobenzo[4,5]imidazo[2, 1-b]quinazolin-1(2 H)-one (Q-NO2). In 1 M hydrochloric acid (HCl), −3,3-dimethyl-3,4,5,12-tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2 H)-one (Q-OMe) proved to be an extremely effective corrosion inhibitor for mild steel. The maximum inhibition efficiencies of 94.7 % for Q-NO2 and 96.7 % for Q-OMe were achieved when the performance of the inhibitors was evaluated using potentiodynamic polarization (PDP), electrochemical frequency modulation (EFM) and electrochemical impedance spectroscopy (EIS). According to these findings, the Q-NO2 and Q-OMe molecules have a remarkable ability to generate a dense, resistant protective film on the mild steel surface. This protective film acted as a barrier, effectively blocking the penetration of corrosive ions and their interaction with the mild steel substrate. The adsorption characteristics of these inhibitors on the mild steel surface conform to the Langmuir adsorption isotherm. PDP experiments show that Q-NO2 and Q-OMe act as mixed-type inhibitors for mild steel in 1.0 M HCl. Surface characterization by energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) determined that a protective layer had formed on the steel surface, preventing corrosion. The experimental results were corroborated by theoretical insights from density functional theory (DFT), which further clarified the molecular adsorption processes. This work highlights the potential of Q-NO2 and Q-OMe as effective inhibitors to protect mild steel in acidic situation.

In-depth study of a newly synthesized imidazole derivative as an eco-friendly corrosion inhibitor for mild steel in 1 M HCl: Theoretical, electrochemical, and surface analysis perspectives

The present study is concerned with the corrosion inhibition and adsorption behaviour of a series of novel imidazole derivatives. The compounds under investigation are 5,5-diphenyl-3-propyl-2-(propylthio)-3,5-dihydro-4 H-imidazol-4-one (AM3) and 3-allyl-2-(allylthio)-5,5-diphenyl-3,5-dihydro-4 H-imidazol-4-one (AM6). The objective of this study is to evaluate the efficacy of 5,5-diphenyl-3,5-dihydro-4 H-imidazol-4-one (AM6) as a corrosion inhibitor on mild steel immersed in a 1.0 M hydrochloric acid medium. This comprehensive study assesses the efficacy of these derivatives through a range of electrochemical and spectroscopic analysis techniques. Additionally, polarisation curves, electrochemical impedance spectroscopy and advanced computer simulations were employed to evaluate the efficacy and inhibition mechanism of imidazole derivatives, thereby facilitating a more profound understanding of their anticorrosive capacity. The results obtained from potentiodynamic polarisation (PDP), electrochemical frequency modulation (EFM) and electrochemical impedance spectroscopy (EIS) measurements demonstrate that the inhibition efficiency increases with increasing imidazole derivative concentration. Conversely, an inverse relationship is observed between inhibition efficiency and temperature. The thermodynamic parameters ΔG°_ads and ΔH°_ads corroborate the conclusion that the adsorption process is predominantly chemical in nature. Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) were employed to characterise the surface morphology. The maximum protection afforded by imidazole derivatives was 95.2 % and 93 % for compounds AM3 and AM6, respectively. Polarisation curves indicated that imidazole derivatives exhibited mixed inhibition behaviour. Surface analysis demonstrated that imidazole derivatives were effectively adsorbed onto the carbon surface, thereby significantly reducing acid damage. This finding was corroborated by DFT calculations, as well as Monte Carlo (MC) and molecular dynamics (MD) simulations. These simulations provided a comprehensive insight into the adsorption of imidazole and its protonated form onto the carbon surface, offering valuable insight into the corrosion inhibition mechanism.

Rotational Spectrum and First Interstellar Detection of 2-methoxyethanol Using ALMA Observations of NGC 6334I

We use both chirped-pulse Fourier transform and frequency-modulated absorption spectroscopy to study the rotational spectrum of 2-methoxyethanol (CH3OCH2CH2OH) in several frequency regions ranging from 8.7 to 500 GHz. The resulting rotational parameters permitted a search for this molecule in Atacama Large Millimeter/submillimeter Array (ALMA) observations toward the massive protocluster NGC 6334I, as well as source B of the low-mass protostellar system IRAS 16293−2422. A total of 25 rotational transitions are observed in the ALMA Band 4 data toward NGC 6334I, resulting in the first interstellar detection of 2-methoxyethanol. A column density of 1.3−0.9+1.4×1017 cm−2 is derived at an excitation temperature of 143−39+31 K. However, molecular signal is not observed in the Band 7 data toward IRAS 16293−2422B, and an upper-limit column density of 2.5 × 1015 cm−2 is determined. Various possible formation pathways—including radical recombination and insertion reactions—are discussed. We also investigate physical differences between the two interstellar sources that could result in the observed abundance variations.

UV photolysis of oxalyl chloride: ClCO radical decomposition and direct Cl2${\rm Cl}_2 {\rm }$ formation pathways

AbstractOxalyl chloride, , is widely used as a photolytic source of Cl atoms in reaction kinetics studies. photolysis is typically assumed to produce Cl atoms with an overall yield of 2 via three‐body dissociation, , followed by fast subsequent ClCO unimolecular decomposition of either the energetically excited fragment, , or the thermalized ClCO radical, . However, a study by Huang et al. (J. Phys. Chem. A 121 (2017) 2888–2895) found that UV photolysis of at directly yields with a photolysis quantum yield of . This new product pathway may complicate the use of as a clean source of Cl atoms and challenges the previously accepted photodissociation scheme. The purpose of the present work was 2‐fold. Firstly, the unimolecular decomposition of and ClCO radicals has been investigated in / gas mixtures after UV photolysis at and . Cl atoms were captured by added in excess such that concentration‐time profiles of HCl measured by means of mid‐infrared frequency modulation spectroscopy reflect the temporally separated Cl formation pathways. The low‐pressure thermal ClCO decomposition rate constant was determined to be at , which is in very good agreement with previously reported literature values. Secondly, the photolysis quantum yield of direct formation from photofragmentation was studied with time‐of‐flight mass spectrometry using a photoelectron photoion coincidence setup. Calibrated concentration‐time profiles were recorded and analyzed using kinetic simulations accounting for both direct and secondary formation of from photolysis and reactions involving Cl, ClCO, and , respectively. Direct formation could be confirmed, where wavelength‐dependent quantum yields of , , and at , , and were determined. Complementary quantum‐chemical calculations of the potential energy diagram for ground‐state photodissociation reveal a low‐lying energy barrier for the formation of phosgene, . We suggest that subsequent and Cl formation from energetically excited may actually play a role for the overall photodissociation of .

Corrosion Inhibition of Expired Cefazolin Drug on Copper Metal in Dilute Hydrochloric Acid Solution: Practical and Theoretical Approaches.

In this work, we studied the corrosion of Cu metal in 0.5 mol L-1 HCl and the inhibition effect of the expired Cefazolin drug. The inhibition efficiency (IE) of Cefazolin varied according to its concentration in solution. As the Cefazolin concentration increased to 300 ppm, the IE increased to 87% at 298 K and decreased to 78% as the temperature increased to 318 K. The expired drug functioned as a mixed-type inhibitor. The adsorption of the drug on the copper surface followed Temkin's adsorption model. The magnitudes of the standard free energy change (ΔGoads) and adsorption equilibrium constant (Kads) indicated the spontaneous nature and exothermicity of the adsorption process. Energy dispersive X-ray (EDX) and scanning electron microscopy (SEM) techniques showed that the drug molecules were strongly attached to the Cu surface. The electrochemical frequency modulation (EFM), potentiodynamic polarization (PP), and electrochemical impedance spectroscopy (EIS) results were in good agreement with the results of the weight loss (WL) method. The density functional tight-binding (DFTB) and Monte Carlo (MC) simulation results indicated that the expired drug bound to the copper surface through the lone pair of electrons of the heteroatoms as well as the π-electrons of the tetrazole ring. The adsorption energy between the drug and copper metal was -459.38 kJ mol-1.

Synthetic FM triplet for AM-free precision laser stabilization and spectroscopy

The Pound–Drever–Hall (PDH) cavity-locking scheme has found prevalent uses in precision optical interferometry and laser frequency stabilization. A form of frequency modulation spectroscopy, PDH enjoys superior signal-to-noise recovery, large acquisition dynamic range, wide servo bandwidth, and robust rejection of spurious effects. However, residual amplitude modulation at the signal frequency, while significantly suppressed, still presents an important concern for further advancing the state-of-the-art performances. Here we present a simplified and improved scheme for PDH using an acousto-optic modulator to generate digital phase reference sidebands instead of the traditionally used electro-optic modulator approach. We demonstrate four key advantages: (1) the carrier and two modulation tones are individually synthesized and easily reconfigured, (2) robust and orthogonal control of the modulated optical field is applied directly to the amplitude and phase quadratures, (3) modulation synthesis, demodulation, and feedback are implemented in a self-contained and easily reproducible electronic unit, and (4) superior active and passive control of residual amplitude modulation is achieved, especially when the carrier power is vanishingly low. These distinct merits stimulate new ideas on how we optimally enact PDH for a wide range of applications.

Advancing frequency locking: Modified FPGA-Guided direct modulation spectroscopy for laser stabilization

In this paper, we propose a cost-effective laser frequency locking scheme based on frequency modulation spectroscopy (FMS) for precision measurements and experiments in various fields. We demonstrate that by digitally modulating the detected signal frequency using a Field-Programmable-Gate-Array (FPGA) driven by a home-built lock-in and a proportional–integral–derivative (PID) control system, our system achieves higher precision, user-friendliness, and versatility. Our system generates a 20 V peak-to-peak amplified voltage to a piezo transducer (PZT), which enables a mode-hop free laser scan of approximately 2 ±0.2 GHz. We directly modulate the detected saturation absorption signal with a sinusoidal waveform, then demodulate it to obtain multiple zero crossing locking points on the D2 transition of Cs at 852.35 nm. We optimized the system for three commonly used atomic transitions and found that researchers can select any of the zero crossing peaks for frequency stabilization depending on their experimental requirements, we locked the laser at the crossover transition. We measured the long-time frequency fluctuation and power spectral density and found that the frequency fluctuation of the laser is much less than the natural line width of the D2 transition of Cs. Our results demonstrate that our laser frequency locking scheme is effective and practical for precision measurements and experiments in various fields.

Self-calibrated NICE-OHMS based on an asymmetric signal: theoretical analysis and experimental validation.

As an ultra-sensitive detection technique, the noise-immune cavity enhanced optical heterodyne molecular spectroscopy (NICE-OHMS) technique has great potential for assessment of the concentration of trace gases. To determine gas concentrations at the ppt or lower level with high accuracy, it is desirable that the technique exhibits self-calibration (or calibration-free) capabilities. Although being sensitive, NICE-OHMS has so far not demonstrated any such ability. To remedy this, this paper provides a self-calibrated realization of NICE-OHMS that is based on a switching of the feedback target of the DeVoe-Brewer (DVB) locking procedure from the modulation frequency of the frequency modulation spectroscopy (FMS) to the cavity length, which creates an asymmetrical signal whose form and size can be used to unambiguously assess the gas concentration. A comprehensive theoretical model for self-calibrated NICE-OHMS is established by analyzing the shift of cavity modes caused by intracavity absorption, demonstrating that gas absorption information can be encoded in both the laser frequency and the NICE-OHMS signal. To experimentally verify the methodology, we measure a series of dispersion signals under different levels of absorbance using a built experimental setup. An instrument factor and the partial pressure are obtained by fitting the measured signal through theoretical expressions. Our results demonstrate that fitted values are more accurate for higher partial pressures than for lower. To improve on the accuracy at low partial pressures, it is shown that the instrument factor obtained by fitting the signal at large partial pressures (in this case, above 7.8 µTorr) can be set to a fixed value for all fits. By this, the partial pressures can be assessed with a relative error below 0.65%. This technique has the potential to enable calibration-free ultra-sensitive gas detection.

Cavity ring-down spectroscopy with a laser frequency stabilized and locked to a reference target gas absorption for drift-free accurate gas sensing measurements

A new gas sensor system with fast response and ultra-high sensitivity has been developed based on a combination of frequency modulation spectroscopy (FMS) and cavity ring-down spectroscopy (CRDS). The system consisted of two distributed feedback laser diodes (DFB-LDs) emitting at frequencies 6251.761 cm-1 (Laser-1) and 6257.762 cm-1 (Laser-2), respectively. A portion of Laser-1’s output was used by a frequency modulation spectroscopy technique to lock its frequency precisely at a CO2 absorption peak, while the rest of its output was coupled to an optical ring-down cavity, together with the Laser-2 output. The Laser-2 operated at a non-absorbing frequency for real-time correction of any baseline ring-down time drift caused by environmental changes (e.g., temperature, pressure). Laser frequency stabilization achieved a 5-fold improvement in CRDS detection sensitivity. This new system was able to make measurements at a data rate of 9 Hz. Based on Allan deviation analysis, the absorbance detection limit of the system was 4.4 × 10−11 cm-1 at an optimum averaging time of ∼5 s, whereas the time-normalized sensitivity at 1 s was 7.3 × 10−11 cm-1/Hz1/2. Measurements of atmospheric CO2 mole fraction were conducted and demonstrated its good performance and reliability. This sensor will be particularly suitable for making drift-free measurements over long periods, in the fields of environmental and industrial gas sensing.

Frequency modulation laser spectroscopy method for methane isotopologue ratio and total concentration measurements at 1661 nm

Source identification and accurate measurements of methane gas concentration are key tools necessary for climate change management. Here we present a method for methane isotopologue ratio measurement using a laser-based frequency modulation (FM) spectroscopy technique in the near infrared at 1661 nm. We provide line shape analysis and discuss a fitting algorithm for accurate isotopologue ratio metrology and investigate and minimize the effects of residual amplitude modulation on the experimentally produced FM signal line shape. This FM technique is further evaluated for future development of a cavity-enhanced and noise-immune system capable of isotopologue ratio as well as ultrasensitive trace gas measurements, all accessible using a single distributed feedback laser.

Design, spectroscopic characterization, DFT, molecular docking, and different applications: Anti-corrosion and antioxidant of novel metal complexes derived from ofloxacin-based Schiff base

A new tridentate Schiff base ligand derived from ofloxacin (oflo) with 2-aminophenol was synthesized and a series of d-transition metal complexes were prepared. The ligand and its metal complexes were investigated using elemental, spectral, and thermal studies. The molecular and electronic structure of the free ligand and its Zn(II) complex were refined theoretically, and the chemical quantum parameters were computed. SEM studies were conducted on the free ligand and its Ni(II) chelate to confirm their nanostructure. The anti-corrosive performance of HL for mild steel (MS) was employed using electrochemical frequency modulation (EFM), potentiodynamic polarization (PP) and electrochemical impedance spectroscopy (EIS) and showed a significant efficiency as anticorrosion agent (89.71%). Molecular docking studies were carried out between the ligand and its [Zn(HL)(H2O)Cl2] complex with active sites of 3T88, 3Q8U, and 3Q7K receptors and the complex showed the strongest binding with 3T88 receptor (-31.9 kcal mol−1). The antioxidant activity of the free ligand and its metal chelates had been carried out using the standard DPPH method and the free ligand showed the highest antioxidant activity (IC50 = 10.52 µg/mL). The in vitro antibacterial activity showed that all prepared compounds were biologically active and Fe(III) complex has the highest inhibiting activity against Proteus Vulgaris Gram-negative bacteria.

Quantum-Enhanced Absorption Spectroscopy with Bright Squeezed Frequency Combs.

Absorption spectroscopy is a widely used technique that permits the detection and characterization of gas species at low concentrations. We propose a sensing strategy combining the advantages of frequency modulation spectroscopy with the reduced noise properties accessible by squeezing the probe state. A homodyne detection scheme allows the simultaneous measurement of the absorption at multiple frequencies and is robust against dispersion across the absorption profile. We predict a significant enhancement of the signal-to-noise ratio that scales exponentially with the squeezing factor. An order of magnitude improvement beyond the standard quantum limit is possible with state-of-the-art squeezing levels facilitating high precision gas sensing.

Influence of blackberry leaf extract on the copper corrosion behaviour in 0.5 M NaCl

The research presented in this paper is focused on blackberry leaf extract (BLE) as a environmentally friendly corrosion inhibitor for copper in 0.5 M NaCl. The caffeic acid, quercetin-3-O-glucoside and kaempferol-3-O-glucoside were identified in BLE by using high-performance liquid chromatography (HPLC-DAD). The BLE functional groups were identified (ATR-FTIR). The electrochemical methods (potentiodynamic polarization, electrochemical frequency modulation and electrochemical impedance spectroscopy) show that BLE acts as a mixed type of inhibitor (max. IE is 97.19 %). The corrosion process is controlled by diffusion (BLE lower than 15 g/L) and charge transfer (15 g/L BLE).

The Influence of Temperature on Frequency Modulation Spectroscopy in Atom Gravimeter.

Atom gravimeters use locked lasers to manipulate atoms to achieve high-precision gravity measurements. Frequency modulation spectroscopy (FMS) is an accurate method of optical heterodyne spectroscopy, capable of the sensitive and rapid frequency locking of the laser. Because of the effective absorption coefficient, Doppler broadening and susceptibility depend on temperature, and the signal-to-noise ratio (SNR) of the spectroscopy could be affected by temperature. We present a detailed study of the influence of the temperature on FMS in atom gravimeters, and the experimental results show that the SNR of the spectroscopy is dependent on temperature. In this paper, the frequency of the reference laser is locked by tracking the set point of the fringe slope of FMS. The influence of the frequency-locking noise of the reference laser on the sensitivity of the atom gravimeter is investigated by changing the temperature of the Rb cell without extra operations. The method presented here could be useful for improving the sensitivity of quantum sensors that require laser spectroscopic techniques.

Mid-infrared Frequency Modulation Detection of HCN and Its Reaction with O Atoms behind Shock Waves.

Hydrogen cyanide (HCN) is the primary cyanide species in combustion processes and plays a key role in the formation of NOx in the combustion of fossil fuels, nitrogen-containing biofuels, and blended hydrocarbon-ammonia mixtures. Robust, sensitive, and time-resolved in situ laser diagnostic methods are needed to gain insight into the combustion chemistry of HCN. Mid-infrared frequency modulation spectroscopy (MIR-FMS) has recently been established as such a quantitative technique for HCN detection behind shock waves. With a minimum detectable fractional absorption of 2 × 10-4 at a time resolution of 5 μs, an improved spectrometer design enabled the detection of HCN behind shock waves down to the ppm mole fraction level. An Allan noise analysis revealed that a further improvement toward shot-noise limited detection should be possible when fast mid-infrared photodetectors with a higher saturation limit will become available. HCN kinetic profiles in the presence of O(3P) atoms from thermal N2O decomposition have been measured in the temperature range 1448 K < T < 1954 K. The determined total rate constants for the key HCN oxidation reaction HCN + O, k/(cm3 mol-1 s-1) = 1.88 × 1014 exp(-64.5 kJ mol-1/RT)(+28%, -37%), turn out to be largely consistent with previous measurements. These data complete the set of available rate constant studies, by now covering the temperature range 450 K < T < 2500 K and relying on the detection of almost all feasible reactant and product species.

Mid-Infrared Frequency Modulation Spectroscopy of NO Detection in a Hollow-Core Antiresonant Fiber

Mid-infrared frequency modulation spectroscopy (FMS) in a tellurite hollow-core antiresonant fiber (HC-ARF) is investigated for gas detection. The spectroscopic system is demonstrated for nitric oxide (NO) detection by exploiting its strong absorption line at 1900.08 cm−1 with a quantum cascade laser (QCL). By modulating the injection current of the QCL at 250 MHz and measuring NO in a 35 cm long HC-ARF, we achieve a noise equivalent concentration of 67 ppb at an averaging time of 0.1 s. Compared to direct absorption spectroscopy with a low-pass filter for etalon noise reduction, the FMS technique shows an improvement factor of 22. The detection limit of FMS can be further improved to 6 ppb at a longer averaging time of 100 s, corresponding to a noise equivalent absorption coefficient of 1.0 × 10−7 cm−1.

Branching fraction measurement of the prompt-NO switch reaction NCN + H

The branching fraction ϕ of the prompt-NO switch reaction NCN + H (1), essentially yielding either CH + N2 (1a) or HCN + N (1b), is key for modeling prompt-NO formation in flames. Large discrepancies exist between available experimental data and flame modeling studies on the one hand and high-level theoretical predictions on the other hand, resulting in a factor of 5 uncertainty for ϕ1b at T=1500 K. By simultaneous monitoring of NCN and HCN concentration-time profiles during the reaction NCN + H at temperatures 1200K<T<2000K behind shock waves, ϕ1b has been directly measured for the first time. Thermal decomposition of cyanogen azide (NCN3) and ethyl iodide (C2H5I) served as sources for NCN radicals and H atoms. NCN has been detected by UV laser absorption at 329.130 nm and HCN detection was accomplished by mid-infrared frequency modulation spectroscopy at 3228.049cm−1. Kinetic simulations provided both the total rate constant k1 from the NCN and k1b from the HCN profiles. In order to account for a side reaction of residual BrCN from NCN3 synthesis, a rough estimate for the rate constant of the reaction BrCN + H was inferred from the experiments as well. The measured rate constants for k1 confirm earlier results (Faßheber et al., Phys. Chem. Chem. Phys. 16 (2014) 11647) and k1b follows the Arrhenius expression k1b/(cm3mol−1s−1)=4.2×1014exp(−38.2kJmol−1/RT) with moderate uncertainties of ±(37−49%). The branching fraction increases with temperature, yielding ϕ1b=0.22(±46%) at 1200 K, 0.47(±42%) at 1600 K, and 0.63(±53%) at 2000 K. The corresponding prompt-NO switch temperature of TS=1670K (ϕ1b=0.5) shows that the reaction NCN + H advances toward the Fenimore products HCN + N already at typical temperatures of hydrocarbon/air flames, in stark contrast to the most recent theoretical estimate reporting TS=3235K.

Optical-feedback cavity-enhanced absorption spectroscopy for OH radical detection at 2.8 µm using a DFB diode laser.

We report the development of an optical-feedback cavity-enhanced absorption spectroscopy (OF-CEAS) instrument for OH detection at 2.8 μm using a DFB diode laser. Two different approaches, symmetry analysis and wavelength modulation, were performed to achieve laser frequency locking to the cavity mode. Compared with the symmetry analysis method, the wavelength modulation method continuously locked the laser frequency to the cavity mode and eliminated decoupling the laser from the cavity mode. A detection sensitivity of 1.7×10-9 cm-1 was achieved in a 25 s sampling time and was about 3 times better than that of the symmetry analysis method. The corresponding OH detection limit was ∼ 2×108 molecule/cm3. Further improvement can be achieved by using higher reflectivity mirrors and other high-sensitivity approaches, such as frequency modulation spectroscopy and Faraday rotation spectroscopy.

Compact plug and play optical frequency reference device based on Doppler-free spectroscopy of rubidium vapor.

Compactness, robustness and autonomy of optical frequency references are prerequisites for reliable operation in mobile systems, on ground as well as in space. We present a standalone plug and play optical frequency reference device based on frequency modulation spectroscopy of the D2-transition in rubidium at 780 nm. After a single button press the hand-sized laser module, based on the micro-integrated laser-optical bench described in [J. Opt. Soc. Am. B38, 1885 (2021)10.1364/JOSAB.420875], works fully autonomous and generates 6 mW of frequency stabilized light with a relative frequency instability of 1.4×10-12 at 1 s and below 10-11 at 105 s averaging time. We describe the design of the device, investigate the thermal characteristics affecting the output frequency and demonstrate short-term frequency stability improvement by a Bayesian optimizer varying the modulation parameters.

Near Infrared and Frequency Modulated Spectroscopy as Non-Invasive Methods for Moisture Assessment of Freeze-Dried Biologics.

Near-infrared (NIR) and frequency modulated spectroscopy (FMS) were employed, for non-invasive moisture determination of a lyophilized biologic drug product (DP). Development of NIR and FMS provides a rapid non-invasive means of residual moisture measurement, and would be beneficial compared with traditional time consuming, product destructive methods such as Karl Fischer (KF). A model therapeutic enzyme in a sucrose-based formulation was employed for proof of concept studies, and NIR and FMS methods were compared side by side for residual moisture analysis. Moisture models were created using lyophilized vials and comparisons were made between the methods using different moisture preparation approaches:1) direct water droplet addition to the vial headspace, 2) use of elevated temperature (80°C), and 3) using various levels of moisture in stoppers generated during the washing and drying procedures, then lyophilizing using the stoppers and placing the sealed vials on stability. The results for direct water addition gave an average percent error for residual moisture of 5.7% for NIR and 9.4% for FMS when compared to KF. The elevated temperature method resulted in an average percent error for residual moisture of 54% for NIR and 43% for FMS compared to KF. The stopper moisture stability study, for FMS, provided an average percent error for residual moisture of 31% compared to KF. The error was greater for the elevated temperature and stopper methods, due to the low moisture values, which resulted in greater error. At this lower range of moisture (<1%) both NIR and FMS were less accurate, but from 1 to 5% their accuracy increased, based on the models used in this study. NIR and FMS methods can be used to complement KF at these lower moisture levels and models could be further improved with additional data points. NIR and FMS methods have advantages and disadvantages for residual moisture analysis when compared to each other, but both provided an accurate measurement of drug product moisture (depending on the method used for moisture increase), they can be used as process analytical technology (PAT), and both can be used for fast non-invasive moisture determination.