Analytical Validation Research Articles

Analytical Modeling and Validation of New Prismatic Compliant Joints Based on Zero Poisson’s Ratio Lattice Structures

Abstract The design and analysis of prismatic compliant joints have received less attention compared to that given to revolute compliant joints, thus limiting their implementation in compliant mechanisms beyond translational stages. Lattice structures have been used effectively to increase flexibility and stiffness ratios in compliant joints. Considering these, new prismatic compliant joints based on zero Poisson’s ratio lattice structures (ZP-PCJ) are proposed. Lattices with three different cell arrangements are considered: single cells, 2×2, and 3×3 lattices. Additionally, unit cells with three different geometries are studied: triangular, chamfer, and cosine. The compliance matrices of the ZP-PCJs are assembled analytically using Castigliano’s second theorem and compliance series–parallel simplification. The compliance ratios along the three orthogonal axes of the ZP-PCJs are computed varying their geometric parameters. Finite element models are constructed to validate the analytical results. Experimental tests are performed on additively manufactured ZP-PCJs to corroborate the compliance coefficients. Results showed that analytical models can predict the ZP-PCJ’s elastic properties accurately, differences less than 3% and 12% were obtained when compared to computational and experiments, respectively. Based on the compliance ratios obtained, the ZP-PCJs are suitable for two-dimensional applications. Finally, the ZP-PCJs are implemented in a compliant mechanism to evaluate their behavior, analytically and computationally. The ZP-PCJs have advantages such as eliminating axis drift and high flexibility in motion-direction while maintaining stiffness in other directions. The differences observed when comparing the analytically obtained estimations with simulations and experimental data suggest that ZP-PCJ analytical models are reliable for estimating their performance in compliant systems.

Analytic validation of convolutional neural network-based classification of pigmented skin lesions (PSLs) using unseen PSL hyperspectral data for clinical applications

Analytic validation of convolutional neural network-based classification of pigmented skin lesions (PSLs) using unseen PSL hyperspectral data for clinical applications

Experimental and theoretical investigation of shear lag effect in twin box‐shaped composite girders of long‐span cable‐stayed bridges

AbstractSteel‐concrete composite box girders offer notable advantages such as high stiffness, excellent torsional performance, and light self‐weight, making them prevalent in large‐span bridges, particularly in cable‐stayed configurations. However, a persistent challenge arises from the shear lag effect in the concrete slab within the flanges induced by shearing interactions between the webs and flanges. Limited attention has been devoted to investigating the experimental and theoretical aspects of shear lag in long‐span cable‐stayed bridges with twin box‐shaped composite girders. This research addresses this gap by designing a segmental scale twin box‐shaped composite model specimen to simulate the cable spacing of the main girder in a cable‐stayed bridge, specifically targeting the shear‐lag effect. The study successfully captures the non‐uniform distribution of cross‐sectional strain in the top concrete slab. Subsequently, analytical strain solutions for the composite girder under mid‐span concentrated load and axial load are derived using the energy variation method. The theoretical model's applicability is then calibrated against experimental results. The investigation extends to the in‐situ testing of the Chibi Yangtze River Bridge, the world's largest steel‐concrete composite girder cable‐stayed bridge, boasting a main span of up to 720 m. An established finite element (FE) analysis model for the Chibi Yangtze River Bridge simulates the transverse stress distribution under typical construction conditions of CC6. Comparative analyses between the simulated results, calculated values from elementary beam theory, and the theoretical model against field‐measured values reveal that the FE model provides a more accurate estimation of the shear lag effect in the concrete slab. Notably, the FE model effectively reflects the bridge's characteristics and serves as a baseline for subsequent studies. This comprehensive investigation contributes significantly to the understanding and analysis of shear lag phenomena in twin box composite girders of cable‐stayed bridges. The integration of experimental, analytical, and construction site validations establishes robust tools for engineering design and the construction of safe and serviceable cable‐stayed bridges. The research augments knowledge regarding shear lag behavior and underscores the necessity to appropriately consider its effects in bridge analysis and design.

Fate of multi-residue insecticides and their metabolites in the process of vinification: Analytical method validation, dissipation kinetics, processing factor, and risk assessment

In viticulture, the use of synthetic chemical formulations introduces insecticide residues into harvested grapes and further into processed grape products, posing a safety concern to consumers. This study investigated the fate of ten insecticide residues and their metabolites from vine to wine. A rapid validated multi-residue approach using QuEChERS extraction and LC-MS/MS configuration was employed for targeted analysis in grape, pomace, and wine. The targeted insecticides showed satisfactory mean recoveries (76.03–111.95%) and precision (RSD = 0.75–7.90%) across the three matrices, with a matrix effect ranging from −16.88 to 35.18%, particularly higher in pomace. Preliminary grape washing effectively removed 15.52–61.31% of insecticide residues based on water solubility and systemic nature. Residue dissipation during fermentation ranged from 73.19% to 87.15% with a half-life spanning from 1 to 5.5 days. The mitigation rate was observed at 12.85–26.81% for wine and 17.76–51.55% for pomace, with the highest transfer rate for buprofezin (51.55%) to pomace and fipronil (25.72%) to wine. Calculated processing factors (PF) for final wine ranged from 0.16 to 0.44, correlating strongly with the octanol-water partition ratio of targeted insecticides. The reported PF, calculated hazard quotient (HQ) (0.003–5.800%), and chronic hazard index (cHI) (2.041–10.387%) indicate reduced residue concentrations in wine and no potential chronic risk to consumers, ensuring a lower dietary risk to wine consumers.

Analytical Method Development and Dermal Absorption of 4-Amino-3-Nitrophenol (4A3NP), a Hair Dye Ingredient under the Oxidative or Non-Oxidative Condition

The chemical 4-amino-3-nitrophenol (4A3NP) is classified as an amino nitrophenol and is primarily utilized as an ingredient in hair dye colorants. In Korea and Europe, it is exclusively used in non-oxidative or oxidative hair dye formulations, with maximum allowable concentrations of 1% and 1.5%, respectively. Despite this widespread use, risk assessment of 4A3NP has not been completed due to the lack of proper dermal absorption data. Therefore, in this study, both the analytical method validation and in vitro dermal absorption study of 4A3NP were conducted following the guidelines provided by the Korea Ministry of Food and Drug Safety (MFDS). Before proceeding with the dermal absorption study, analytical methods were developed for the quantitation of 4A3NP through multiple reaction monitoring (MRM) via liquid chromatography-mass spectrometry (LC-MS) in various matrices, including swab wash (WASH), stratum corneum (SC), skin (SKIN, comprising the dermis and epidermis), and receptor fluid (RF). These developed methods demonstrated excellent linearity (R2 = 0.9962–0.9993), accuracy (93.5–111.73%), and precision (1.7–14.46%) in accordance with the validation guidelines.The dermal absorption of 4A3NP was determined using Franz diffusion cells with mini-pig skin as the barrier. Under both non-oxidative and oxidative (6% hydrogen peroxide (H2O2): water, 1:1) hair dye conditions, 1% and 1.5% concentrations of 4A3NP were applied to the skin at a rate of 10 μL/cm2, respectively. The total dermal absorption rates of 4A3NP under non-oxidative (1%) and oxidative (1.5%) conditions were determined to be 5.62 ± 2.19% (5.62 ± 2.19 μg/cm2) and 2.83 ± 1.48% (4.24 ± 2.21 μg/cm2), respectively.

Development and validation of RP-HPLC method for simultaneous estimation of 5-fluorouracil and silibinin in corn-derived protein-polysaccharide nanocomplex: Forced degradation and mathematical modeling of drug release

In the current work, RP-HPLC method was developed and validated for simultaneous analysis of 5-Fluorouracil (5-FU) and silibinin from corn-derived protein polysaccharide nanocomplex. The method employs a mobile phase of water (A) and acetonitrile: methanol (60:40) (B) on a Waters C18 column (4.6 x 150 mm, 5 μm), with detection wavelengths set at 266 nm and 288 nm for 5-FU and silibinin, respectively. The runtime was 15 min at a flow rate of 0.7 mL/min. The analytical method validation adhered closely to ICH guidelines, exhibiting remarkable selectivity, specificity, linearity, and precision, all falling comfortably within acceptable thresholds. The analytical method was found to be linear from 1 to 150 µg/mL with R2 of 0.9998. Forced degradation studies were carried to assess the stability of 5-FU and silibinin within the nanocomplex across diverse conditions. Additionally, nanocomplexes loaded with 5-FU and silibinin were formulated and characterized, demonstrating a particle size of 209.83 ± 3.83 nm and a zeta potential of 57.93 ± 1.06 mV. The %entrapment efficiency for 5-FU and silibinin was found to be 88.73 ± 0.37 % and 97.00 ± 1.58 % with a %drug loading of 6.73 ± 0.92 % and 2.74 ± 0.61 % respectively. The %in vitro drug release was determined using developed and validated analytical methods. Further, various release kinetic models were applied to determine the release behavior from the nanocomplex system. To conclude, we ensured the eco-friendliness of the developed analytical method by assessing its greenness through Eco-scale, the green analytical procedure index (GAPI), and the Analytical GREEnness metric (AGREE).

Abstract PO5-14-03: Analytical Validation of the StemPrintER Assay in Patients with Breast Cancer

Abstract Discussion: Breast cancer is the most common malignancy diagnosed amongst women, with more the two million new cases identified globally each year. Thus, considerable resources have been devoted to a better understanding of the disease and how to optimize outcomes for patients. Genetics and genomics have become part of routine care with the latter used to inform treatment planning for patients with ER+ breast cancer (ER+ BC). A multitude of assays may be used to determine the need for adjuvant chemotherapy but none of the current tests on the market are guideline-recommended for making decisions related to neoadjuvant chemotherapy, surgery, or radiation. The 24-gene StemPrintER assay was developed to measure the “stemness” of tumors, or how much a tumor behaves like stem cells, which could have important and novel implications for breast cancer treatment planning. The assay has been validated for predicting prognosis using formalin-fixed paraffin-embedded (FFPE) tissue blocks from several clinical cohorts, including TransATAC. The goal of current and future research will be to determine whether the assay can determine the ideal surgical intervention for ER+BC patients. Early in silico work demonstrated a trend toward this predictive capacity for the assay and suggests the assay may be able to identify the benefit of mastectomy versus quadrantectomy. Here, we report on the ability to set up and run the assay in our lab using synthetic oligonucleotides and archival tissue blocks. Methods: Synthetic oligonucleotides and archival FFPE breast cancer tissue were used to set up and analytically validate the assay’s performance in two phases. The initial phase was intended to confirm the individual assay design performance by assessing linearity and precision and the ability to amplify RNA from FFPE, which confirmed compatibility with standard extraction methods. The second phase was intended to determine whether these methods could be implemented to reliably extract and amplify RNA from FFPE >10 years old (range: 10-14 years) in order to generate a StemPrintER score. The assay was run according to standard operating procedures for StemPrintER. Analyses were conducted Python 3.9.12. Results: Two assay runs with duplicate samples for each run using a 7-point dilution series demonstrated linearity (coefficient of correlation, r2) results ranging from 0.978 to 0.999 for each of the 24 genes in the assay. Amplification efficiency was between 100-101% for each gene. Using 14 FFPE samples from patients with triple-negative breast cancer, we demonstrated a consistent extraction yield of RNA from tumor blocks which produced amplification of each of the targets. Analysis of intra- and inter-run precision resulted in coefficients of variation (CV) ranging from 0.2-1.07% and inter-run CV’s ranging from 0.66%-5.56%. Utilizing FFPE >10 years old from ER+BC patients demonstrated that the lab could extract RNA from 100% of samples and amplify the material to obtain binary StemPrintER results. Conclusion: These data demonstrate that StemPrintER can be run reliably on FFPE tissue up to 14 years old. In addition, our laboratory has demonstrated that assay results are highly linear and reproducible. Additional studies are planned to build on preliminary surgical prediction data and determine whether the assay can meet the unmet need of identifying the ideal surgical intervention in patients with early-stage ER+/HER2- breast cancer. Citation Format: Catie Cronister, Brock Schweitzer, Hannah Gilmore, Tyler Nielsen. Analytical Validation of the StemPrintER Assay in Patients with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-14-03.

Case report: Asymptomatic celiac disease patient discovered during analytical validation

Case report: Asymptomatic celiac disease patient discovered during analytical validation

Characterization and Quantitation of a Sulfoconjugated Metabolite for Detection of Methyltestosterone Misuse and Direct Identification by LC-MS

Methyltestosterone (MT) is one of the most frequently misused anabolic androgenic steroids detected in doping control analysis. The metabolism of MT in humans leads to several phase І metabolites and their corresponding phase Ⅱ conjugates.Previous studies have postulated the 3α-sulfoconjugate of 17α-methyl-5β-androstane-3α,17β-diol (S2) as principal sulfate metabolite of MT, with a detection window exceeding 10 days. However, a final direct and unambiguous confirmation of the structure of this metabolite is missing until now. In this study, we established an approach to detect and identify S2, using intact analysis by liquid chromatography hyphenated with tandem mass spectrometry (LC-MS/MS) without complex sample pretreatment. An in vitro study yielded the LC-MS/MS reference retention times of all 3-sulfated 17-methylandrostane-3,17-diol diastereomers, allowing for accurate structure assignment of potentially detected metabolites. In an in vivo excretion study with a single healthy male volunteer, the presence of the metabolite S2 was confirmed after a single oral dose of 10mg MT. The reference standard was chemically synthesized, characterized by accurate mass mass spectrometry (MS) and nuclear magnetic resonance (NMR), and quantified by quantitative qNMR. Thus, this study finally provides accurate structure information on the S2 metabolite and a direct analytical method for detection of MT misuse. The availability of the reference material is expected to be of benefit for further evaluation and subsequent analytical method validation in anti-doping research.

Biomarker panels: Analytical and clinical validation against clinically relevant reference standards

Biomarker panels: Analytical and clinical validation against clinically relevant reference standards

Homogenization Model for Multistable Honeycomb Metastructures with Beam-like Behavior

Reduced order models facilitate initial design space investigations and enable assessing the benefits of compliant structures utilized for shape adaptability. This work presents a simple model to determine the flexural rigidity of a beam-like, multistable metastructure used as a spar in a hybrid spanwise morphing wing. The model considers the more complex metabeam as a homogeneous beam described by Euler-Bernoulli beam theory with an equivalent flexural rigidity. The analytical model's validity is established by comparing the obtained static and dynamic responses to finite element simulations. A closed-form expression of the flexural rigidity is then given, drawing from the multistable honeycomb's material properties and the metabeam’s geometry. The model's limitations are addressed by examining several specific cases of the metabeam’s morphed configurations and a more complex metabeam structure.

Analysis of Trace Impurities in Lithium Carbonate.

Lithium carbonate (Li2CO3) is a critical raw material in cathode material production, a core of Li-ion battery manufacturing. The quality of this material significantly influences its market value, with impurities potentially affecting Li-ion battery performance and longevity. While the importance of impurity analysis is acknowledged by suppliers and manufacturers of battery materials, reports on elemental analysis of trace impurities in Li2CO3 salt are scarce. This study aims to establish and validate an analytical methodology for detecting and quantifying trace impurities in Li2CO3 salt. Various analytical techniques, including X-ray diffraction (XRD), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma optical emission spectroscopy (ICP-OES), were employed to analyze synthetic and processed lithium salt. X-ray diffraction patterns of Li2CO3 were collected via step-scanning mode in the 5-80° 2θ range. SEM-EDX was utilized for particle morphology and quantitative impurity analysis, with samples localized on copper tape. XPS equipped with a hemispherical electron analyzer was employed to analyze the surface composition of the salt. For ICP-OES analysis, a known amount of lithium salt was subjected to acid digestion and dilution with ultrapure water. Multielemental standard solutions were prepared, including elements such as Al, Cd, Cu, Fe, Mn, Ni, Pb, Si, Zn, Ca, K, Mg, Na, and S. Results confirmed the presence of the zabuyelite phase in XRD analysis, corresponding to the natural form of lithium carbonate. SEM-EDX mapping revealed impurities of Si and Al, with low relative quantification values of 0.12% and 0.14%, respectively. XPS identified eight potential impurity elements, including S, Cr, Fe, Cl, F, Zn, Mg, and Na, alongside Li, O, and C. Regarding ICP-OES analysis, performance parameters such as linearity, limit of detection (LOD), and quantification (LOQ), variance, and recovery were evaluated for analytical validation. ICP-OES results demonstrated high linearity (>0.99), with LOD and LOQ values ranging from 0.001 to 0.800 ppm and 0.003 to 1.1 ppm, respectively, for different elements. The recovery rate exceeded 90%. In conclusion, the precision of the new ICP-OES methodology renders it suitable for identifying and characterizing Li2CO3 impurities. It can effectively complement solid-state techniques such as XRD, SEM-EDX, and XPS.

[Chinese expert consensus on the analytical validation of tumor comprehensive genomic profiling next generation sequencing testing (2024 edition)].

In hospital laboratories-developed testing is of great significance for the clinical testing products that has not been approved by the National Medical Product Administration and is urgently needed to meet clinical practice needs. With the development of cancer precision medicine in recent years, comprehensive genomic profiling (CGP) has become an important means and method for the detection of drug targets, precise molecular typing, and immunotherapy biomarkers in cancer patients. However, there is still a lack of unified understanding and consensus on clinical testing standards and application specifications for laboratory-developed testing in the hospitals. The Molecular Pathology Collaboration Group of the Cancer Experts Committee of the Chinese Anti-Cancer Association and the Molecular Pathology Group of the Pathology Branch of the Chinese Medical Association initiated the expert consensus on relevant specifications for analytical validation of CGP next-generation sequencing (NGS) testing in Chinese hospitals. Combined with domestic clinical practice, refer to domestic and foreign literatures, from the background of the laboratory-developed testing, analytical validation scenarios, evaluation indicators and variation ranges, sample types and quantities covered by analytical validation, clinical performance and drug efficacy determination, and site personnel for analytical validation, quality control, inter-laboratory quality evaluation and document management, etc. After the discussion by the expert group, 12 expert consensuses were formed to provide reference for the analytical validation and clinical application of tumor CGP NGS testing in Chinese hospitals, so as to promote the laboratory-developed testing applications in Chinese hospitals.

Advancing cortisol measurements in zebrafish: Analytical validation of a commercial ELISA kit for skin mucus cortisol analysis

Cortisol is the main stress biomarker used for zebrafish. However, zebrafish small size made it challenging to extract cortisol without harming or killing the fish. Thus, researchers adopted a terminal method, the trunk cortisol, as standard practice. Here, we developed and validated an alternative and minimally invasive technique for measuring cortisol in the skin mucus of adult zebrafish, using a commercial enzyme-linked immunosorbent assay (ELISA). For this, AB zebrafish were randomly assigned to a precision, accuracy, and specificity test. Each sample contained the skin mucus of five to ten fish or one fish trunk. The cortisol was extracted using methanol as organic solvent. The results obtained showed an adequate precision (intra-assay coefficient of variation (CV) <15%; inter-assay CV = 26%), accuracy (CV <120%), and specificity (r2 =0.96–0.98) for skin mucus cortisol levels, as well as for trunk cortisol.•A commercial ELISA was analytically validated to measure cortisol in the skin mucus of zebrafish.•Skin mucus cortisol is a non-terminal method that reduce the number of animals used and allows longitudinal studies.

Organophosphate esters and their metabolites in marine fish from Vietnam: Analytical method development and validation

Organophosphate esters (tri-OPEs), which are a significant group of emerging organic pollutants, have been widely found in aquatic products worldwide. While tri-OPEs have been extensively detected in aquatic products and are known to represent potential risks to human health, there is limited information available regarding their metabolites (di-OPEs). Currently, the techniques for analyzing the composition of tri- and di-OPEs have been distinguished and have certain drawbacks in terms of their expense, time requirements, and reliability. The objective of the study is to develop, validate, and utilize a modified QuEChERS technique for extracting tri- and di-OPEs in marine fish. As a result, EMR-Lipid and WAX were selected as adsorbents for the QuEChERS method to purify the samples and a combination of centrifugal vacuum and nitrogen at a temperature of 1 °C was selected as a technique to enhance the sensitivity of the developed method. The parameters of the method validation are in accordance with the criteria specified in SANTE/11312/2021 (a recovery ranging from 84.0% to 107.4% and RSD of precision below 20%). The aforementioned methodology was employed to assess the tri-OPEs and their metabolites in a total of 72 fish muscle samples obtained from the presence of OPEs in all recorded instances. The average concentration of ΣOPEs was determined to be 87.4±55.0 ng/g dw, with TBOEP and BEHP identified as the predominant compounds. Furthermore, no significant variation in the content of tri- and di-OPEs was observed in fish samples, regardless of species or geographical location.

[Standardization of next-generation sequencing for detecting mutations associated with targeted therapy and immunotherapy based on dynamic pattern of expandable detection range].

Next-generation sequencing (NGS) has laid the foundation for precision oncology care. NGS technologynot only represents an innovation in the methodology but also brings about a revolution in the concept of detecting gene alterations for targeted therapy and immunotherapy of cancers. As basic biomedical research and drug development progress, the landscape of biomarkers associated with gene alterations continues to evolve. Thus, the standardization of NGS-based gene alterations detection should take into account the characteristics of NGS methods and the gene alteration biomarkers. To be specific, whether employed as in vitro diagnostic products or laboratory-developed tests, the detection range can be expanded in response to changes in the clinical evidence level of biomarkers during the process of assay development and clinical application. Such adjustment needs the analytical validation results for supplemented genes or mutant sites within a predefined detection system, which will maximally fulfill the evolving clinical demands in cancer diagnosis and treatment, simultaneously mitigate potential risks effectively. This article primarily discusses the standardization pathway for NGS testing of gene alterations in cancer by focusing on the characteristics of NGS methods, gene alteration biomarkers, and the current status of the standardization of NGS application.

Analytical Method Development and Validation of Brivaracetam in API and Marketed Formulation by RP-HPLC

A rapid and precise reverse phase high performance liquid chromatographic method has been developed for the validated of brivaracetam in its pure form as well as in tablet dosage form. Chromatography was carried out on a Symmetry ODS RP C18,5mm, 15mm x 4.6mm column using a mixture of phosphate buffer: methanol: acetonitrile (30:35:35% v/v) as the mobile phase at a flow rate of 1.0ml/min, the detection was carried out at 285 nm. The retention time of the brivaracetam was 2.183. The method produces linear responses in the concentration range of 60-140μg/ml of brivaracetam. The method precision for the determination of assay was below 2.0%RSD. The method was found to be sensitive, accurate and precise useful in the quality control of bulk and pharmaceutical formulations.  

A Novel Methodology for Developing Smartphone-instrumented Tests for Assessing Movement, Dexterity, and Balance in Neurological Patients: Technical Verification of Ground Truth Datasets, and Analytical and Clinical Validation of Digital Biomarkers (P6-6.009)

A Novel Methodology for Developing Smartphone-instrumented Tests for Assessing Movement, Dexterity, and Balance in Neurological Patients: Technical Verification of Ground Truth Datasets, and Analytical and Clinical Validation of Digital Biomarkers (P6-6.009)

Analytical and Clinical Validation of β-Amyloid 1–40, 1–42, and the 1–42/1–40 Ratio Using a Clinical Autoanalyzer (P3-9.014)

Analytical and Clinical Validation of β-Amyloid 1–40, 1–42, and the 1–42/1–40 Ratio Using a Clinical Autoanalyzer (P3-9.014)

Experimental investigation of high-frequency transverse instability in Helmholtz resonator-coupled lean-premixed hydrogen combustor

Recent experimental studies suggest that lean-premixed pure hydrogen combustion plays a central role in generating self-sustained pressure oscillations, preferentially coupled with high-frequency tangential modes in land-based gas turbine combustors. The triggering of such high-frequency combustion dynamics is known to be closely connected with relatively small, flashback-resistant, characteristic nozzle dimensions, and the structural and kinematic properties of the premixed hydrogen flames. To identify important trends in the transverse modal dynamics of hydrogen flames, here we conduct detailed measurements of multislit injector-driven hydrogen flame dynamics. We analyze the measured data using the wave decomposition technique for PDF-based statistical assessments of bimodality and nodal line orientation. Experimentally, the planar-to-transverse mode transformation is revealed to be controlled by the combined influence of flame temperature and thermal power, which ultimately leads to the development of well-defined standing modes at around 4.69 kHz under the most severe test condition. Using analytic modeling and rigorous validation measurements, we also investigate Helmholtz resonator-type passive stabilization and its impact on the integrated system's thermoacoustic states with respect to the change in purge air flowrate. Our results show that the coupled system does not retain many of the initial thermoacoustic properties, but instead undergoes prominent changes in the first tangential modal dynamics, progressively evolving from a large-amplitude bimodal to a low-amplitude unimodal state.