Real-time Near-infrared Research Articles

Evaluation of Analytical and Sampling Errors in the Prediction of the Active Pharmaceutical Ingredient Concentration in Blends From a Continuous Manufacturing Process

A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis. Thirty-three calibration blends were prepared in laboratory scale equipment with a concentration range spanning from 70 to 130% of API target concentration. The NIR calibration model was validated using three independent validation sets (prepared in laboratory and pilot plant facilities and in the CM equipment). Real-time NIR spectra were obtained with an interface where three NIR spectrometers monitored the CM process. A variographic study was performed with the NIR predictions of drug concentration in blends. A total of 1800 NIR spectra were obtained throughout a CM run that lasted 2.5 h. Two NIR spectrometers (M1 and M2) monitored the CM run while located in positions b-1 and b-3 of the sensing interface. These two positions yielded very similar results. The average NIR predictions for blends were 101.67% LC for the first run using spectrometer M1 and 103.60% LC with M2. The second run provided an average NIR prediction of 101.19% LC with M1 and 103.16% LC with M2. The average drug concentration in tablets was 100.63% LC for the first run and 100.42% LC for the second run. Variograms showed a low sill and a flat, stable variogram demonstrating good mixing of the blend. The CM process provided tablets with excellent content uniformity. The sampling and analytical errors and the true process variation were easily discerned through variographic analysis.

Photosensitizer-conjugated tryptophan-containing peptide ligands as new dual-targeted theranostics for cancers

Here we report that new dual-targeted theranostic anti-cancer agents can be produced by simple conjugation of photosensitizers with tryptophan-containing peptide ligands via cyclic disulfide linkages. In the proof-of-concept study, photosensitizers conjugated with EGFR-targeting peptide GE11 (C-EGFR) were in close proximity with tryptophan residues in the conjugate, resulting in quenching of its fluorescence and singlet oxygen generation. C-EGFR specifically binds to target receptors on the cancer cell surface, after which it is internalized via receptor-mediated endocytosis. Intracellular cleavage of cyclic disulfide bonds allows separation of the photosensitizers from the tryptophan residue, after which they emit near-infrared (NIR) fluorescence and produce a phototoxic effect in the target cells. This strategy enabled us to accomplish simultaneous real-time NIR fluorescence imaging of EGFR-overexpressing cancer cells with high contrast and selective photodynamic therapy

Near infrared spectroscopy to monitor drug release in-situ during dissolution tests

Dissolution tests can be used to demonstrate suitable in vivo drug release through in vivo/in vitro correlations. This work explores the possibility of using near infrared spectroscopy (NIRS) to monitor in-situ dissolution tests. It aims at expanding surrogate methods in quality control of drug products. Laboratory designed tablets of an immediate-release formulation containing folic acid and four excipients were used as case study. The dissolution tests were performed on a 1L vessel filled with 500ml of Milli-Q water with a rotating paddle apparatus (apparatus 2, Ph. Eur.) at 50rpm and 37±0.5°C. Near infrared (NIR) spectra were acquired in-situ with a transflectance probe connected to a Fourier-transform near infrared spectrometer. NIR spectra were regressed against folic acid concentration by partial least squares (PLS) regression. Folic acid concentrations during dissolution tests were obtained by periodically sampling the dissolution vessel and resourcing to an UV method. The proposed real-time NIR method was tested on a validation run yielding a root mean squared error of 0.25μgml−1 (0.16μgml−1 for the calibration runs) and a R2 of 0.93 (0.95 for the calibration runs). The results suggest that NIRS is a suitable analytical technique for monitoring in-situ dissolution tests.

Near-infrared indocyanine dye permits real-time characterization of both venous and lymphatic circulation

We investigated the optical properties of a near-infrared (NIR) fluorochrome, di-β-cyclodextrin-binding indocyanine derivative (TK-1), and its pharmacokinetic differences with indocyanine green (ICG). TK-1 was designed to have hydrophilic cyclodextrin molecules and, thus, for higher water solubility and smaller particle sizes than the plasma protein-bound ICG. We compared optical properties such as the absorption and fluorescence spectra, quantum yield, and photostability between both dyes in vitro. In addition, we subcutaneously injected a 1 mM solution of TK-1 or ICG into the hind footpad of rats and observed real-time NIR fluorescence intensities in their femoral veins and accompanying lymphatics at the exposed groin site to analyze the dye pharmacokinetics. These optical experiments demonstrated that TK-1 has high water solubility, a low self-aggregation tendency, and high optical and chemical stabilities. Our in vivo imaging showed that TK-1 was transported via peripheral venous flow and lymphatic flow, whereas ICG was drained only through lymphatics. The results of this study showed that lymphatic and venous transport can be differentially regulated and is most likely influenced primarily by particle size, and that TK-1 can enable real-time NIR fluorescence imaging of whole fluids and solute movement via both microvessels and lymphatics, which conventional ICG cannot achieve.

Intraoperative Near-infrared Imaging for Parathyroid Gland Identification by Auto-fluorescence: A Feasibility Study.

Parathyroid glands (PGs) can be particularly hard to distinguish from surrounding tissue and thus can be damaged or removed during thyroidectomy. Postoperative hypoparathyroidism is the most common complication after thyroidectomy. Very recently, it has been found that the parathyroid tissue shows near-infrared (NIR) auto-fluorescence which could be used for intraoperative detection, without any use of contrast agents. The work described here presents a histological validation ex vivo of the NIR imaging procedure and evaluates intraoperative PG detection by NIR auto-fluorescence using for the first time to our knowledge a commercially available clinical NIR imaging device. Ex vivo study on resected operative specimens combined with a prospective in vivo study of consecutive patients who underwent total or partial thyroid, or parathyroid surgery at a comprehensive cancer center. During surgery, any tissue suspected to be a potential PG by the surgeon was imaged with the Fluobeam 800 (®) system. NIR imaging was compared to conventional histology (ex vivo) and/or visual identification by the surgeon (in vivo). We have validated NIR auto-fluorescence with an ex vivo study including 28 specimens. Sensitivity and specificity were 94.1 and 80%, respectively. Intraoperative NIR imaging was performed in 35 patients and 81 parathyroids were identified. In 80/81 cases, the fluorescence signal was subjectively obvious on real-time visualization. We determined that PG fluorescence is 2.93±1.59 times greater than thyroid fluorescence in vivo. Real-time NIR imaging based on parathyroid auto-fluorescence is fast, safe, and non-invasive and shows very encouraging results, for intraoperative parathyroid identification.

Real-time NIR imaging of Palm Dorsa subcutaneous vein pattern based biometrics: An SRC based approach

With the advancement in biometric recognition techniques, Palm Dorsa Subcutaneous Vein Pattern (PDSVP) [1] has emerged as a reliable and promising physiological biometric feature. Consequently, PDSVP has been extensively used as a biometric feature in recent research works on biometrics. However, the procedure of automatic data acquisition and PDSVP extraction is quite challenging. This article shows how this problem can be addressed in practice where a real life biometric identification system has been developed utilising near infrared (NIR) imaging of PDSVP of humans, where no fixed setup is employed for data acquisition. We highlight, in this article, three key ideas: automatic data acquisition, PDSVP extraction and, subsequently, biometric person identification using sparse representation based classification. Finally, we highlight the research challenges associated with implementing a Biometric Identification System (BIS) using PDSVP as a physiological feature.

Cancer cell membrance-functionalized nanoparticles for homotypic-targeted cancer imaging and highly effective photothermal therapy

Cell membrance-coated nanoparticles (NPs) have been garnering increased attention due to the NPs possessing many desirable features, including red blood cell-derived NPs with long-circulating capabilities, leukocyte membrance-coated particles with traverse endothelium abilities, cancer cell membrane-cloaked NPs with homotypic targeting properties. Herein, we fabricated indocyanine green (ICG) loaded poly(lactic-co-glycolic acid) (PLGA)-cancer cell membrance NPs (IPCNPs) using a single-step sonication method. PLGA was selected for the core to encapsulated the near-infrared (NIR) imaging/photothermal agent (ICG), and the PLGA core coated with MCF-7 breast cancer cell membrance and (1, 2-distearoylsn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000]) (DSPEPEG-COOH). The IPCNPs exhibited good monodispersity, excellent size/fluorescence stability, preferable temperature response under laser irradiation, real-time NIR fluorescence imaging, and excellent homotypic targeting to MCF-7 cells. In vitro cell viability assays indicated that IPCNPs could efficiently suppressed MCF-7 cells under laser irradiation by taking advantage of the inherent homotypic binding phenomenon. Thus, we had developed novel theranostic NPs that combined photothermal therapy with homotypic-targeting activation.

Assessment of powder blend uniformity: Comparison of real-time NIR blend monitoring with stratified sampling in combination with HPLC and at-line NIR Chemical Imaging

Scope of the study was (1) to develop a lean quantitative calibration for real-time near-infrared (NIR) blend monitoring, which meets the requirements in early development of pharmaceutical products and (2) to compare the prediction performance of this approach with the results obtained from stratified sampling using a sample thief in combination with off-line high pressure liquid chromatography (HPLC) and at-line near-infrared chemical imaging (NIRCI). Tablets were manufactured from powder blends and analyzed with NIRCI and HPLC to verify the real-time results. The model formulation contained 25% w/w naproxen as a cohesive active pharmaceutical ingredient (API), microcrystalline cellulose and croscarmellose sodium as cohesive excipients and free-flowing mannitol. Five in-line NIR calibration approaches, all using the spectra from the end of the blending process as reference for PLS modeling, were compared in terms of selectivity, precision, prediction accuracy and robustness. High selectivity could be achieved with a “reduced” approach i.e. API and time saving approach (35% reduction of API amount) based on six concentration levels of the API with three levels realized by three independent powder blends and the additional levels obtained by simply increasing the API concentration in these blends. Accuracy and robustness were further improved by combining this calibration set with a second independent data set comprising different excipient concentrations and reflecting different environmental conditions. The combined calibration model was used to monitor the blending process of independent batches. For this model formulation the target concentration of the API could be achieved within 3min indicating a short blending time. The in-line NIR approach was verified by stratified sampling HPLC and NIRCI results. All three methods revealed comparable results regarding blend end point determination. Differences in both mean API concentration and RSD values could be attributed to differences in effective sample size and thief sampling errors. This conclusion was supported by HPLC and NIRCI analysis of tablets manufactured from powder blends after different blending times. In summary, the study clearly demonstrates the ability to develop efficient and robust quantitative calibrations for real-time NIR powder blend monitoring with a reduced set of powder blends while avoiding any bias caused by physical sampling.

Real-time, near-infrared fluorescence imaging with an optimized dye/light source/camera combination for surgical guidance of prostate cancer.

The prostate-specific membrane antigen (PSMA) is a surface glycoprotein overexpressed on malignant prostate cells, as well as in the neovasculature of many tumors. Recent efforts to target PSMA for imaging prostate cancer rely on suitably functionalized low-molecular-weight agents. YC-27 is a low-molecular-weight, urea-based agent that enables near-infrared (NIR) imaging of PSMA in vivo. We have developed and validated a laparoscopic imaging system (including an optimized light source, LumiNIR) that is capable of imaging small tumor burdens with minimal background fluorescence in real-time laparoscopic extirpative surgery of small prostate tumor xenografts in murine and porcine models. In a mouse model, we demonstrate the feasibility of using real-time NIR laparoscopic imaging to detect and surgically remove PSMA-positive xenografts. We then validate the use of our laparoscopic real-time NIR imaging system in a large animal model. Our novel light source, which is optimized for YC-27, is capable of detecting as little as 12.4 pg/mL of the compound (2.48-pg YC-27 in 200-μL agarose). Finally, in a mouse xenograft model, we demonstrate that the use of real-time NIR imaging can reduce positive surgical margins (PSM). These data indicate that a NIR-emitting fluorophore targeted to PSMA may allow improved surgical treatment of human prostate cancer, reduce the rate of PSMs, and alleviate the need for adjuvant radiotherapy postoperatively.

A Near-Infrared Face Detection and Recognition System Using ASM and PCA+LDA

Near-infrared (NIR) images have a lot of advantages, which can make up the shortages of visible light (VL) images. A novel NIR detection and recognition system is presented in this paper. First, a NIR imaging system is developed to provide good illumination conditions for subsequent face detection and recognition. Then, Active Shape Model (ASM) method is applied to detect the features and the low-dimensional Gabor features are extracted for recognition by combining Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA). The recognition rate of the system is up to 90% in a few milliseconds. Finally, by using such real-time NIR face recognition system, comparative results are provided, from that we can seen that this system can work robustly and effectively

Near-infrared fluorescence cholangiopancreatoscopy: initial clinical feasibility results

The recent clinical propagation of targeted fluorescence agents brings a promising alternative in endoscopy by complementing visual disease detection with molecular biomarkers. Development of near-infrared (NIR) fluorescence cholangiopancreatoscopy in real-time and validation of its clinical use. Feasibility study. Tertiary referral center at a large university hospital. Patients with pancreatic and biliary diseases. Routine cholangiopancreatoscopy with additional wide-field NIR fluorescence imaging. We adapted a miniature cholangioscope for real-time concurrent wide-field color and NIR fluorescence imaging. Illumination is provided through a custom-designed fiber bundle, and the acquired images are relayed via a dichroic beam splitter to 2 charge-coupled devices for simultaneous measurement. We characterize the sensitivity and resolution and demonstrate the clinical feasibility by detecting indocyanine green localization in 2 patients. A spatial optical resolution of approximately 50 μm was achieved, and fluorescent dye concentrations of 17.3 nM could be detected. Elevated fluorescence signals were detected during clinical measurements, and biopsy specimens confirmed the presence of malignancy in both patients. Feasibility study, limited number of patients. The results demonstrate that real-time wide-field fluorescence detection in the NIR range is possible in humans by using adapted endoscopes. The feasibility of detecting indocyanine green in the pancreatobiliary ducts is verified, suggesting that cancer screening at a molecular level might play an increasingly important role in the future.

A novel multivariate approach using science-based calibration for direct coating thickness determination in real-time NIR process monitoring

This study demonstrates an approach, using science-based calibration (SBC), for direct coating thickness determination on heart-shaped tablets in real-time. Near-Infrared (NIR) spectra were collected during four full industrial pan coating operations. The tablets were coated with a thin hydroxypropyl methylcellulose (HPMC) film up to a film thickness of 28μm. The application of SBC permits the calibration of the NIR spectral data without using costly determined reference values. This is due to the fact that SBC combines classical methods to estimate the coating signal and statistical methods for the noise estimation. The approach enabled the use of NIR for the measurement of the film thickness increase from around 8 to 28μm of four independent batches in real-time. The developed model provided a spectroscopic limit of detection for the coating thickness of 0.64±0.03μm root-mean square (RMS). In the commonly used statistical methods for calibration, such as Partial Least Squares (PLS), sufficiently varying reference values are needed for calibration. For thin non-functional coatings this is a challenge because the quality of the model depends on the accuracy of the selected calibration standards. The obvious and simple approach of SBC eliminates many of the problems associated with the conventional statistical methods and offers an alternative for multivariate calibration.

Identification of metastatic nodal disease in a phase 1 dose-escalation trial of intraoperative sentinel lymph node mapping in non–small cell lung cancer using near-infrared imaging

Early-stage non-small cell lung cancer (NSCLC) has a high recurrence rate and poor 5-year survival, particularly if lymph nodes are involved. Our objective was to perform a dose-escalation study to assess safety and feasibility of intraoperative near-infrared (NIR) fluorescence imaging to identify the first tumor-draining lymph nodes (ie, sentinel lymph nodes [SLNs] in patients with NSCLC). A-dose escalation phase 1 clinical trial assessing real-time NIR imaging after peritumoral injection of 3.8 to 2500 μg indocyanine green (ICG) was initiated in patients with suspected stage I/II NSCLC. Visualization of lymphatic migration, SLN identification, and adverse events were recorded. Thirty-eight patients underwent ICG injection and NIR imaging via thoracotomy (n = 18) or thoracoscopic imaging (n = 20). SLN identification increased with ICG dose, with fewer than 25% SLNs detected in dose cohorts of 600 μg or less versus 89% success at 1000 μg or greater. Twenty-six NIR(+) SLNs were identified in 15 patients, with 7 NIR(+) SLNs (6 patients) harboring metastatic disease on histologic analysis. Metastatic nodal disease was never identified in patients with a histologically negative NIR(+) SLN. No adverse reactions were noted. NIR-guided SLN identification with ICG was safe and feasible in this initial dose-escalation trial. ICG doses greater than 1000 μg yielded nearly 90% intrathoracic SLN visualization, with the presence or absence of metastatic disease in the SLN directly correlating with final nodal status of the lymphadenectomy specimen. Further studies are needed to optimize imaging parameters and confirm sensitivity and specificity of SLN mapping in NSCLC using this promising imaging technique.

A Haemodynamic Brain–Computer Interface Based on Real-Time Classification of near Infrared Spectroscopy Signals during Motor Imagery and Mental Arithmetic

Over the past decade, an increasing number of studies have investigated near infrared (NIR) spectroscopy for signal acquisition in brain–computer interface (BCI) systems. However, although a BCI relies on classifying brain signals in real-time, the majority of previous studies did not perform real-time NIR spectroscopy signal classification but derived knowledge about the feasibility of NIR spectroscopy for BCI purposes from offline analyses. The present study investigates whether NIR spectroscopy signals evoked by two different mental tasks (i.e. motor imagery and mental arithmetic) can be classified in real-time in order to control a NIR-BCI application. Furthermore, since this is the first study that attempts to distinguish between the haemodynamic responses to these two tasks, we aimed to investigate whether this task-combination is feasible for controlling a NIR-BCI. Twelve healthy participants were asked to control a moving ball on a computer screen by performing motor imagery and mental arithmetic tasks. The real-time classification of their task-specific NIR spectroscopy signals yielded accuracy rates ranging from 45% up to 93%. Offline analyses across all participants showed that both tasks evoked different haemodynamic responses in prefrontal and sensorimotor cortex areas. On the one hand, these results demonstrate the considerable potential of NIR spectroscopy for BCI signal acquisition and the feasibility of the applied mental tasks for NIR-BCI control. On the other hand, since the classification accuracy showed an unsatisfactory stability across measurement sessions, we conclude that further investigations and progress in methodological issues are needed and we discuss further steps that have to be taken until it is conceivable to implement a real-time capable NIR-BCI that works with sufficient accuracy across a large group of individuals.

Real-time predictions of drug release and end point detection of a coating operation by in-line near infrared measurements

The aim of this work was to carry out real-time near infrared (NIR) predictions of drug release from sustained release coated tablets and to determine end point of coating operation.In-line measurements were ensured by implementation of a NIR probe inside a pan coater. Tablets were coated using a functional aqueous dispersion of ethylcellulose blended with PVA–PEG graft copolymer to obtain a controlled drug release dosage form over 16h. Samples were collected at regular intervals and subjected to a standardized curing step. Percentages of released drug at 4h, 8h and 12h were selected to describe the controlled drug release of cured tablets. These dissolution criteria were used as reference values to calibrate NIR spectral information and to develop three partial least squares regressions.Low predictive errors of 1.7%, 1.9% and 1.5%, respectively, were obtained. The coating operation was stopped while desired dissolution criteria were achieved, corresponding to a coating level around 10%.The present study demonstrated that real-time NIR measurements could be performed on non-finished drug products to predict dissolution properties of cured coated tablets. This novel and innovative approach fulfils the expectations of ICH Q8 guideline on pharmaceutical development, in terms of process understanding and process analytical technology (PAT) control strategy. This approach should be however adapted to curing operation to allow a real-time release testing.

Image-guided tumor resection using real-time near-infrared fluorescence in a syngeneic rat model of primary breast cancer

Tumor involvement of resection margins is found in a large proportion of patients who undergo breast-conserving surgery. Near-infrared (NIR) fluorescence imaging is an experimental technique to visualize cancer cells during surgery. To determine the accuracy of real-time NIR fluorescence imaging in obtaining tumor-free resection margins, a protease-activatable NIR fluorescence probe and an intraoperative camera system were used in the EMR86 orthotopic syngeneic breast cancer rat model. Influence of concentration, timing and number of tumor cells were tested in the MCR86 rat breast cancer cell line. These variables were significantly associated with NIR fluorescence probe activation. Dosing and tumor size were also significantly associated with fluorescence intensity in the EMR86 rat model, whereas time of imaging was not. Real-time NIR fluorescence guidance of tumor resection resulted in a complete resection of 17 out of 17 tumors with minimal excision of normal healthy tissue (mean minimum and a mean maximum tumor-free margin of 0.2 ± 0.2 mm and 1.3 ± 0.6 mm, respectively). Moreover, the technique enabled identification of remnant tumor tissue in the surgical cavity. Histological analysis revealed that the NIR fluorescence signal was highest at the invasive tumor border and in the stromal compartment of the tumor. In conclusion, NIR fluorescence detection of breast tumor margins was successful in a rat model. This study suggests that clinical introduction of intraoperative NIR fluorescence imaging has the potential to increase the number of complete tumor resections in breast cancer patients undergoing breast-conserving surgery.

Nanotechnology in Thoracic Surgery

Nanotechnology is an exciting and rapidly progressing field offering potential solutions to multiple challenges in the diagnosis and treatment of lung cancer, with the potential for improving imaging and mapping techniques, drug delivery, and ablative therapy. With promising preclinical results in many applications directly applicable to thoracic oncology, it is possible that the frontiers of minimally invasive thoracic surgery will eventually be explored at the nanoscale.

Real‐time Visualization and Quantification of Retrograde Cardioplegia Delivery using Near Infrared Fluorescent Imaging

Homogeneous delivery of cardioplegia is essential for myocardial protection during cardiac surgery. Presently, there exist no established methods to quantitatively assess cardioplegia distribution intraoperatively and determine when retrograde cardioplegia is required. In this study, we evaluate the feasibility of near infrared (NIR) imaging for real-time visualization of cardioplegia distribution in a porcine model. A portable, intraoperative, real-time NIR imaging system was utilized. NIR fluorescent cardioplegia solution was developed by incorporating indocyanine green (ICG) into crystalloid cardioplegia solution. Real-time NIR imaging was performed while the fluorescent cardioplegia solution was infused via the retrograde route in five ex vivo normal porcine hearts and in five ex vivo porcine hearts status post left anterior descending (LAD) coronary artery ligation. Horizontal cross-sections of the hearts were obtained at proximal, middle, and distal LAD levels. Videodensitometry was performed to quantify distribution of fluorophore content. The progressive distribution of cardioplegia was clearly visualized with NIR imaging. Complete visualization of retrograde distribution occurred within 4 minutes of infusion. Videodensitometry revealed retrograde cardioplegia, primarily distributed to the left ventricle (LV) and anterior septum. In hearts with LAD ligation, antegrade cardioplegia did not distribute to the anterior LV. This deficiency was compensated for with retrograde cardioplegia supplementation. Incorporation of ICG into cardioplegia allows real-time visualization of cardioplegia delivery via NIR imaging. This technology may prove useful in guiding intraoperative decisions pertaining to when retrograde cardioplegia is mandated.

Real-time on-line blend uniformity monitoring using near-infrared reflectance spectrometry: A noninvasive off-line calibration approach

A robust, noninvasive, real-time, on-line near-infrared (NIR) quantitative method is described for blend uniformity monitoring of a pharmaceutical solid dosage form containing 29.4% (w/w) drug load with three major excipients (crospovidone, lactose, and microcrystalline cellulose). A set of 21 off-line, static calibration samples were used to develop a multivariate partial least-squares (PLS) calibration model for on-line prediction of the API content during the blending process. The concentrations of the API and the three major excipients were varied randomly to minimize correlations between the components. A micro electrical-mechanical system (MEMS) based portable, battery operated NIR spectrometer was used for this study. To minimize spectral differences between the static and dynamic measurement modes, the acquired NIR spectra were preprocessed using standard normal variate (SNV) followed by second derivative Savitzky-Golay using 21 points. The performance of the off-line PLS calibration model were evaluated in real-time on 16 laboratory scale (30 L bin size) blend experiments conducted over 3 months. To challenge the robustness of the off-line calibration model, several blend experiments were conducted using a different bin size, faster revolution speed and variations in the potency of the API. Employing the PLS calibration model developed using the off-line calibration approach, the real-time API NIR (%) predictions for all experiments were all within 90–110%. These results were confirmed using the conventional thief sampling of the final blend followed by high performance liquid chromatography (HPLC) analysis. Further confirmation was established through content uniformity by HPLC of manufactured tablets. Finally, the optimized off-line PLS method was successfully transferred to a production site which involved using a secondary NIR instrument with a 15-fold scale-up in bin size from development.

Numerical simulation to correlate photopolymerization kinetics monitoring by RT-NIR spectroscopy and photocalorimetry

Photocalorimetry (DSC) and real time infrared (RTIR) spectroscopy are the two usual methods used to follow photopolymerization reactions. Kinetics obtained by DSC on thin samples and kinetics obtained by real time near-infrared (RT-NIR) spectroscopy on thick samples are not the same. The heat release during the photopolymerization induced a high temperature increase in thick samples because of the absence of temperature control. We think that this temperature offset is the main cause of this kinetic difference. In this paper, we want to verify this assumption. To reach this aim, conversion and temperature evolutions versus time were numerically simulated for a sample placed in the thermal conditions of NIR analysis by using experimental kinetic data obtained by photocalorimetry in isothermal mode. The boundary conditions were determined such as the simulated evolution of the sample temperature is the same as the experimental one. At last, conversion curves simulated to obtain these temperature profiles were compared to experimental results obtained by RT-NIR.