Evaluating Vascular Depth-Dependent Changes in Multi-Wavelength PPG Signals Due to Contact Force.

Photoplethysmography (PPG) is a non-invasive method used for cardiovascular monitoring, with multi-wavelength PPG (MW-PPG) enhancing its efficacy by using multiple wavelengths for improved assessment. This study explores how contact force (CF) variations impact MW-PPG signals. Data from 11 healthy subjects are analyzed to investigate the still understudied specific effects of CF on PPG signals. The obtained dataset includes simultaneous recording of five PPG wavelengths (470, 525, 590, 631, and 940 nm), CF, skin temperature, and the tonometric measurement derived from CF. The evolution of raw signals and the PPG DC and AC components are analyzed in relation to the increasing and decreasing faces of the CF. Findings reveal individual variability in signal responses related to skin and vasculature properties and demonstrate hysteresis and wavelength-dependent responses to CF changes. Notably, all wavelengths except 631 nm showed that the DC component of PPG signals correlates with CF trends, suggesting the potential use of this component as an indirect CF indicator. However, further validation is needed for practical application. The study underscores the importance of biomechanical properties at the measurement site and inter-individual variability and proposes the arterial pressure wave as a key factor in PPG signal formation.

Evaluation of the TraumaGuard Balloon-in-Balloon Catheter Design for Intra-Abdominal Pressure Monitoring: Insights from Pig and Human Cadaver Studies.

Introduction: Intra-abdominal pressure (IAP) monitoring is crucial for the detection and prevention of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). In the 1970s, air-filled catheters (AFCs) for urodynamic studies were introduced as a solution to overcome the limitations of water-perfused catheters. Recent studies have shown that for correct IAP measurement with traditional AFC, the bladder needs to be primed with 25 mL of saline solution to allow pressure wave transmission to the transducer outside of the body, which limits continuous IAP monitoring. Methods: In this study, a novel triple balloon, air-filled TraumaGuard (TG) catheter system from Sentinel Medical Technologies (Jacksonville, FL, USA) with a unique balloon-in-balloon design was evaluated in a porcine and cadaver model of IAH via laparoscopy (IAPgold). Results: In total, 27 and 86 paired IAP measurements were performed in two pigs and one human cadaver, respectively. The mean IAPTG was 20.7 ± 10.7 mmHg compared to IAPgold of 20.3 ± 10.3 mmHg in the porcine study. In the cadaver investigation, the mean IAPTG was 15.6 ± 10.8 mmHg compared to IAPgold of 14.4 ± 10.4 mmHg. The correlation, concordance, bias, precision, limits of agreement, and percentage error were all in accordance with the WSACS (Abdominal Compartment Society) recommendations and guidelines for research. Conclusions: These findings support the use of the TG catheter for continuous IAP monitoring, providing early detection of elevated IAP, thus enabling the potential for prevention of IAH and ACS. Confirmation studies with the TraumaGuard system in critically ill patients are warranted to further validate these findings.

In Vitro Validation of a Novel Continuous Intra-Abdominal Pressure Measurement System (TraumaGuard).

Introduction: Intra-abdominal pressure (IAP) has been recognized as an important vital sign in critically ill patients. Due to the high prevalence and incidence of intra-abdominal hypertension in surgical (trauma, burns, cardiac) and medical (sepsis, liver cirrhosis, acute kidney injury) patients, continuous IAP (CIAP) monitoring has been proposed. This research was aimed at validating a new CIAP monitoring device, the TraumaGuard from Sentinel Medical Technologies, against the gold standard (height of a water column) in an in vitro setting and performing a comparative analysis among different CIAP measurement technologies (including two intra-gastric and two intra-bladder measurement devices). A technical and clinical guideline addressing the strengths and weaknesses of each device is provided as well. Methods: Five different CIAP measurement devices (two intra-gastric and three intra-vesical), including the former CiMON, Spiegelberg, Serenno, TraumaGuard, and Accuryn, were validated against the gold standard water column pressure in a bench-top abdominal phantom. The impacts of body temperature and bladder fill volume (for the intra-vesical methods) were evaluated for each system. Subsequently, 48 h of continuous monitoring (n = 2880) on top of intermittent IAP (n = 300) readings were captured for each device. Using Pearson's and Lin's correlations, concordance, and Bland and Altman analyses, the accuracy, precision, percentage error, correlation and concordance coefficients, bias, and limits of agreement were calculated for all the different devices. We also performed error grid analysis on the CIAP measurements to provide an overview of the involved risk level due to wrong IAP measurements and calculated the area under the curve and time above a certain IAP threshold. Lastly, the robustness of each system in tracking the dynamic variations of the raw IAP signal due to respirations and heartbeats was evaluated as well. Results: The TraumaGuard was the only technology able to measure the IAP with an empty artificial bladder. No important temperature dependency was observed for the investigated devices except for the Spiegelberg, which displayed higher IAP values when the temperature was increased, but this could be adjusted through recalibration. All the studied devices showed excellent ability for IAP monitoring, although the intra-vesical IAP measurements seem more reliable. In general, the TraumaGuard, Accuryn, and Serenno showed better accuracy compared to intra-gastric measurement devices. On average, biases of +0.71, +0.93, +0.29, +0.25, and -0.06 mm Hg were observed for the CiMON, Spiegelberg, Serenno, TraumaGuard, and Accuryn, respectively. All of the equipment showed percentage errors smaller than 25%. Regarding the correlation and concordance coefficients, the Serenno and TraumaGuard showed the best results (R2 = 0.98, p = 0.001, concordance coefficient of 99.5%). Error grid analysis based on the Abdominal Compartment Society guidelines showed a very low associated risk level of inappropriate treatment strategies due to erroneous IAP measurements. Regarding the dynamic tracings of the raw IAP signal, all the systems can track respiratory variations and derived parameters; however, the CiMON was slightly superior compared to the other technologies. Conclusions: According to the research guidelines of the Abdominal Compartment Society (WSACS), this in vitro study shows that the TraumaGuard can be used interchangeably with the gold standard for measuring continuous IAP, even in an empty artificial bladder. Confirmation studies with the TraumaGuard in animals and humans are warranted to further validate these findings.

Anomaly Detection in Multi-Wavelength Photoplethysmography Using Lightweight Machine Learning Algorithms.

Over the past few years, there has been increased interest in photoplethysmography (PPG) technology, which has revealed that, in addition to heart rate and oxygen saturation, the pulse shape of the PPG signal contains much more valuable information. Lately, the wearable market has shifted towards a multi-wavelength and multichannel approach to increase signal robustness and facilitate the extraction of other intrinsic information from the signal. This transition presents several challenges related to complexity, accuracy, and reliability of algorithms. To address these challenges, anomaly detection stages can be employed to increase the accuracy and reliability of estimated parameters. Powerful algorithms, such as lightweight machine learning (ML) algorithms, can be used for anomaly detection in multi-wavelength PPG (MW-PPG). The main contributions of this paper are (a) proposing a set of features with high information gain for anomaly detection in MW-PPG signals in the classification context, (b) assessing the impact of window size and evaluating various lightweight ML models to achieve highly accurate anomaly detection, and (c) examining the effectiveness of MW-PPG signals in detecting artifacts.

Novel Multi-Parametric Sensor System for Comprehensive Multi-Wavelength Photoplethysmography Characterization.

Photoplethysmography (PPG) is widely used to assess cardiovascular health. However, its usage and standardization are limited by the impact of variable contact force and temperature, which influence the accuracy and reliability of the measurements. Although some studies have evaluated the impact of these phenomena on signal amplitude, there is still a lack of knowledge about how these perturbations can distort the signal morphology, especially for multi-wavelength PPG (MW-PPG) measurements. This work presents a modular multi-parametric sensor system that integrates continuous and real-time acquisition of MW-PPG, contact force, and temperature signals. The implemented design solution allows for a comprehensive characterization of the effects of the variations in these phenomena on the contour of the MW-PPG signal. Furthermore, a dynamic DC cancellation circuitry was implemented to improve measurement resolution and obtain high-quality raw multi-parametric data. The accuracy of the MW-PPG signal acquisition was assessed using a synthesized reference PPG optical signal. The performance of the contact force and temperature sensors was evaluated as well. To determine the overall quality of the multi-parametric measurement, an in vivo measurement on the index finger of a volunteer was performed. The results indicate a high precision and accuracy in the measurements, wherein the capacity of the system to obtain high-resolution and low-distortion MW-PPG signals is highlighted. These findings will contribute to developing new signal-processing approaches, advancing the accuracy and robustness of PPG-based systems, and bridging existing gaps in the literature.

Feasibility analysis of a novel non-invasive ultrasonographic method for the measurement of intra-abdominal pressure in the intensive care unit.

Increased intra-abdominal pressure (IAP) is an important vital sign in critically ill patients and has a negative impact on morbidity and mortality. This study aimed to validate a novel non-invasive ultrasonographic approach to IAP measurement against the gold standard intra-bladder pressure (IBP) method. We conducted a prospective observational study in an adult medical ICU of a university hospital. IAP measurements using ultrasonography by two independent operators, with different experience levels (experienced, IAPUS1; inexperienced, IAPUS2), were compared with the gold standard IBP method performed by a third blinded operator. For the ultrasonographic method, decremental external pressure was applied on the anterior abdominal wall using a bottle filled with decreasing volumes of water. Ultrasonography looked at peritoneal rebound upon brisk withdrawal of the external pressure. The loss of peritoneal rebound was identified as the point where IAP was equal to or above the applied external pressure. Twenty-one patients underwent 74 IAP readings (range 2-15 mmHg). The number of readings per patient was 3.5 ± 2.5, and the abdominal wall thickness was 24.6 ± 13.1 mm. Bland and Altman's analysis showed a bias (0.39 and 0.61 mmHg) and precision (1.38 and 1.51 mmHg) for the comparison of IAPUS1 and IAPUS2 and vs. IBP, respectively with small limits of agreement that were in line with the research guidelines of the Abdominal Compartment Society (WSACS). Our novel ultrasound-based IAP method displayed good correlation and agreement between IAP and IBP at levels up to 15 mmHg and is an excellent solution for quick decision-making in critically ill patients.

Indirect Calorimetry in Spontaneously Breathing, Mechanically Ventilated and Extracorporeally Oxygenated Patients: An Engineering Review.

Indirect calorimetry (IC) is considered the gold standard for measuring resting energy expenditure (REE). This review presents an overview of the different techniques to assess REE with special regard to the use of IC in critically ill patients on extracorporeal membrane oxygenation (ECMO), as well as to the sensors used in commercially available indirect calorimeters. The theoretical and technical aspects of IC in spontaneously breathing subjects and critically ill patients on mechanical ventilation and/or ECMO are covered and a critical review and comparison of the different techniques and sensors is provided. This review also aims to accurately present the physical quantities and mathematical concepts regarding IC to reduce errors and promote consistency in further research. By studying IC on ECMO from an engineering point of view rather than a medical point of view, new problem definitions come into play to further advance these techniques.

Fluid Management, Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome: A Narrative Review.

BACKGROUND: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. OBJECTIVES: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). METHODS: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. RESULTS: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. CONCLUSIONS: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

Pre-Clinical Validation of A Novel Continuous Intra-Abdominal Pressure Measurement Equipment (SERENNO).

Introduction: Increased intra-abdominal pressure (IAP) has an important impact on morbidity and mortality in critically ill patients. The SERENNO Sentinel system (Serenno Medical, Yokne'am Illit, Israel) is a novel device that allows automatic and continuous IAP measurements. Aims: Pre-clinical validation in a bench model study comparing the new device with the gold standard method and two other continuous IAP measurement devices. Methods: IAP measurement with the novel SERENNO device (IAPSER) was compared with the gold standard IAPH2O (water column height) and two other automatic and continuous IAP measurement devices: IAPCiM measured via the CiMON device (Pulsion Medical Systems, Munich, Germany) and IAPSPIE measured using the Spiegelberg device (Spiegelberg, Hamburg, Germany), which previously received the CE mark for clinical applications. The IAP measurement was performed six times (n = 6) at each pressure value (between 0 and 35 mmHg) with different methods and the height of the water column in a bench-top phantom was used as the reference IAP for further interpretations. In addition to the quadruple comparisons, intra- and inter-observer variability of IAP measurements were also calculated. Correlation studies and Bland and Altman's analyses were performed in addition to the concordance study. Results: The CiMON and Spiegelberg devices showed a greater dynamic range and standard deviation when recording IAPCiM and IAPSPIE compared with IAPSER. In general, the maximum and minimum values of IAP recorded with each device (at each level of IAPH2O) were significantly different from each other. However, the average values were in very good agreement. The highest correlation was observed between IAPSER and IAPH2O, and IAPSER and IAPSPIE (R = 0.99, p = 0.001 for both comparisons and intra- and inter-observer measurements). Although the CiMON and SERENNO systems were in very good agreement with each other, a slightly smaller correlation coefficient was found between them (R = 0.95, p = 0.001, and R = 0.96, p = 0.001 for intra- and inter-observer measurements, respectively). When compared to the gold standard (IAPH2O), Bland and Altman's analysis showed a mean difference of +0.44, -0.25, and -0.04 mmHg for the intra-observer measurements and +0.18, -0.75, and -0.58 mmHg for the inter-observer measurements for IAPSER, IAPCiM, and IAPSPIE, respectively. IAPSER showed a small positive bias (overestimation), while IAPCiM and IAPSPIE showed a negative bias (underestimation) when compared to IAPH2O. Further statistical analysis showed a concordance coefficient of 100% with an excellent ability of the SERENNO system in tracking IAPH2O changes. Conclusions: Pre-clinical validation of a new IAP monitoring device (SERENNO) showed very promising results when compared with the gold standard and other continuous techniques; however, clinical trials should be followed as the next stage of the validation process. Based on the actual research guidelines, the SERENNO system can be used interchangeably with the gold standard.

A Novel Approach to Non-Destructive Rubber Vulcanization Monitoring by the Transient Radar Method.

Rubber is one of the most used materials in the world; however, raw rubber shows a relatively very low mechanical strength. Therefore, it needs to be cured before its ultimate applicatios. Curing process specifications, such as the curing time and temperature, influence the material properties of the final cured product. The transient radar method (TRM) is introduced as an alternative for vulcanization monitoring in this study. Three polyurethane-rubber samples with different curing times of 2, 4, and 5.5 min were studied by TRM to investigate the feasibility and robustness of the TRM in curing time monitoring. Additionally, the mechanical stiffness of the samples was investigated by using a unidirectional tensile test to investigate the potential correlations between curing time, dielectric permittivity, and stiffness. According to the results, the complex permittivity and stiffness of the samples with 2, 4, and 5.5 min of curing time was 17.33 ± 0.07 - (2.41 ± 0.04)j; 17.09 ± 0.05 - (4.90 ± 0.03)j; 23.60 ± 0.05 - (14.06 ± 0.06)j; and 0.29, 0.35, and 0.38 kPa, respectively. Further statistical analyses showed a correlation coefficient of 0.99 (p = 0.06), 0.80 (p = 0.40), and 0.92 (p = 0.25) between curing time-stiffness, curing time-permittivity (real part), and curing time-permittivity (imaginary part), respectively. The correlation coefficient between curing time and permittivity can show the potential of the TRM system in contact-free vulcanization monitoring, as the impact of vulcanization can be tracked by means of TRM.

PPG EduKit: An Adjustable Photoplethysmography Evaluation System for Educational Activities.

The grown interest in healthcare applications has made biomedical engineering one of the fastest growing disciplines in recent years. Photoplethysmography (PPG) has gained popularity in recent years due to its versatility for noninvasive monitoring of vital signs such as heart rate, respiratory rate, blood oxygen saturation and blood pressure. In this work, an adjustable PPG-based educational device called PPG EduKit, which aims to facilitate the learning of the PPG technology for a wide range of engineering and medical disciplines is proposed. Through the use of this educational platform, the PPG signal can be understood, modified and implemented along with the extraction of its relevant physiological information from a didactic, intuitive and practical way. The PPG Edukit is evaluated for the extraction of physiological parameters such as heart rate and blood oxygen level, demonstrating how its features contribute to engineering and medical students to assimilate technical concepts in electrical circuits, biomedical instrumentation, and human physiology.

Non-Invasive Intra-Abdominal Pressure Measurement by Means of Transient Radar Method: In Vitro Validation of a Novel Radar-Based Sensor.

Intra-abdominal hypertension, defined as an intra-abdominal pressure (IAP) equal to or above 12 mmHg is one of the major risk-factors for increased morbidity (organ failure) and mortality in critically ill patients. Therefore, IAP monitoring is highly recommended in intensive care unit (ICU) patients to predict development of abdominal compartment syndrome and to provide a better care for patients hospitalized in the ICU. The IAP measurement through the bladder is the actual reference standard advocated by the abdominal compartment society; however, this measurement technique is cumbersome, non-continuous, and carries a potential risk for urinary tract infections and urethral injury. Using microwave reflectometry has been proposed as one of the most promising IAP measurement alternatives. In this study, a novel radar-based method known as transient radar method (TRM) has been used to monitor the IAP in an in vitro model with an advanced abdominal wall phantom. In the second part of the study, further regression analyses have been done to calibrate the TRM system and measure the absolute value of IAP. A correlation of -0.97 with a p-value of 0.0001 was found between the IAP and the reflection response of the abdominal wall phantom. Additionally, a quadratic relation with a bias of -0.06 mmHg was found between IAP obtained from the TRM technique and the IAP values recorded by a pressure gauge. This study showed a promising future for further developing the TRM technique to use it in clinical monitoring.

A concise overview of non-invasive intra-abdominal pressure measurement techniques: from bench to bedside.

This review presents an overview of previously reported non-invasive intra-abdominal pressure (IAP) measurement techniques. Each section covers the basic physical principles and methodology of the various measurement techniques, the experimental results, and the advantages and disadvantages of each method. The most promising non-invasive methods for IAP measurement are microwave reflectometry and ultrasound assessment, in combination with an applied external force.

Error Assessment and Mitigation Methods in Transient Radar Method.

Transient Radar Method (TRM) was recently proposed as a novel contact-free method for the characterization of multilayer dielectric structures including the geometric details. In this paper, we discuss and quantify the intrinsic and systematic errors of TRM. Also, solutions for mitigating these problems are elaborated extensively. The proposed solution for error correction will be applied to quantify experimentally the thickness of several single-layer dielectric structures with thicknesses varying from larger to smaller than the wavelength. We will show how the error correction method allows sub-wavelength thickness measurements around λ / 5 .

Natural Compounds Therapeutic Features in Brain Disorders by Experimental, Bioinformatics and Cheminformatics Methods.

BACKGROUND: Synthetic compounds with pharmaceutical applications in brain disorders are daily designed and synthesized, with well first effects but also seldom severe side effects. This imposes the search for alternative therapies based on the pharmaceutical potentials of natural compounds. The natural compounds isolated from various plants and arthropods venom are well known for their antimicrobial (antibacterial, antiviral) and antiinflammatory activities, but more studies are needed for a better understanding of their structural and pharmacological features with new therapeutic applications. OBJECTIVES: Here we present some structural and pharmaceutical features of natural compounds isolated from plants and arthropods venom relevant for their efficiency and potency in brain disorders. We present the polytherapeutic effects of natural compounds belonging to terpenes (limonene), monoterpenoids (1,8-cineole) and stilbenes (resveratrol), as well as natural peptides (apamin, mastoparan and melittin). METHODS: Various experimental and in silico methods are presented with special attention on bioinformatics (natural compounds database, artificial neural network) and cheminformatics (QSAR, drug design, computational mutagenesis, molecular docking). RESULTS: In the present paper we reviewed: (i) recent studies regarding the pharmacological potential of natural compounds in the brain; (ii) the most useful databases containing molecular and functional features of natural compounds; and (iii) the most important molecular descriptors of natural compounds in comparison with a few synthetic compounds. CONCLUSION: Our paper indicates that natural compounds are a real alternative for nervous system therapy and represents a helpful tool for the future papers focused on the study of the natural compounds.

Compressed Sensing mm-Wave SAR for Non-Destructive Testing Applications Using Multiple Weighted Side Information.

This work explores an innovative strategy for increasing the efficiency of compressed sensing applied on mm-wave SAR sensing using multiple weighted side information. The approach is tested on synthetic and on real non-destructive testing measurements performed on a 3D-printed object with defects while taking advantage of multiple previous SAR images of the object with different degrees of similarity. The tested algorithm attributes autonomously weights to the side information at two levels: (1) between the components inside the side information and (2) between the different side information. The reconstruction is thereby almost immune to poor quality side information while exploiting the relevant components hidden inside the added side information. The presented results prove that, in contrast to common compressed sensing, good SAR image reconstruction is achieved at subsampling rates far below the Nyquist rate. Moreover, the algorithm is shown to be much more robust for low quality side information compared to coherent background subtraction.

Selective changes in locomotor activity in mice due to low-intensity microwaves amplitude modulated in the EEG spectral domain.

Despite the numerous benefits of microwave applications in our daily life, microwaves were associated with diverse neurological complaints such as headaches and impaired sleep patterns, and changes in the electroencephalogram (EEG). To which extent microwaves influence the brain function remains unclear. This exploratory study assessed the behavior and neurochemistry in mice immediately or 4weeks after a 6-day exposure to low-intensity 10-GHz microwaves with an amplitude modulation (AM) of 2 or 8Hz. These modulation frequencies of 2 and 8Hz are situated within the delta and theta-alpha frequency bands in the EEG spectrum and are associated with sleep and active behavior, respectively. During these experiments, the specific absorbance rate was 0.3W/kg increasing the brain temperature with 0.23°C. For the first time, exposing mice to 8-Hz AM significantly reduced locomotor activity in an open field immediately after exposure which normalized after 4weeks. This in contrast to 2-Hz AM which didn't induce significant changes in locomotor activity immediately and 4weeks after exposure. Despite this difference in motor behavior, no significant changes in striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels and DOPAC/DA turnover nor in cortical glutamate (GLU) concentrations were detected. In all cases, no effects on motor coordination on a rotarod, spatial working memory, anxiety nor depressive-like behavior were observed. The outcome of this study indicates that exposing mice to low-intensity 8-Hz AM microwaves can alter the locomotor activity in contrast to 2-Hz AM which did not affect the tested behaviors.

Interinstrumental method transfer of a capillary electrophoretic separation of angiotensin II and five derivatives: Evaluation and update of earlier developed guidelines.

The increased interest in the separation of peptides, proteins, immunoglobulins, and polynucleotides, led to an increased demand for appropriate analytical methodologies and instrumentation. CE, because of its unique separation mechanism and high efficiency, is frequently used in the analysis of those molecules. In this study, a CE method for the separation of six angiotensin analogues was developed in the first step. In the second step, the method was transferred to a CE instrument of another brand, taking into account guidelines defined earlier about the interinstrumental transfer of CE methods. Although previously successful, the application of these guidelines during this study was not able to maintain the baseline separation. Further research on the instrumental differences revealed that the electrical resistance on both instruments differed. At constant current, the electrical resistance, generated voltage, and separation efficiency on the Agilent instrument were lower than on the Beckman instrument. Increase of the electrical resistance, by reducing the capillary temperature, leads to an increased applied voltage and separation efficiency on the Agilent system. The guidelines developed earlier were, therefore, updated with an additional step equalizing the electrical resistances, which led to a successful interinstrumental analytical method transfer for the separation of six angiotensin derivatives.

Inter-instrumental method transfer of chiral capillary electrophoretic methods using robustness test information.

Capillary electrophoresis (CE) is an electrodriven separation technique that is often used for the separation of chiral molecules. Advantages of CE are its flexibility, low cost and efficiency. On the other hand, the precision and transfer of CE methods are well-known problems of the technique. Reasons for the more complicated method transfer are the more diverse instrumental differences, such as total capillary lengths and capillary cooling systems; and the higher response variability of CE methods compared to other techniques, such as liquid chromatography (HPLC). Therefore, a larger systematic change in peak resolutions, migration times and peak areas, with a loss of separation and efficiency may be seen when a CE method is transferred to another laboratory or another type of instrument. A swift and successful method transfer is required because development and routine use of analytical methods are usually not performed in the same laboratory and/or on the same type of equipment. The aim of our study was to develop transfer rules to facilitate CE method transfers between different laboratories and instruments. In our case study, three ß-blockers were chirally separated and inter-instrumental transfers were performed. The first step of our study was to optimise the precision of the chiral CE method. Next, a robustness test was performed to identify the instrumental and experimental parameters that were most influencing the considered responses. The precision- and the robustness study results were used to adapt instrumental and/or method settings to improve the transfer between different instruments. Finally, the comparison of adapted and non-adapted transfers allowed deriving some rules to facilitate CE method transfers.