Monitoring with In Vivo Electrochemical Sensors: Navigating the Complexities of Blood and Tissue Reactivity

The disruptive action of an acute or critical illness is frequently manifest through rapid biochemical changes that may require continuous monitoring. Within these changes, resides trend information of predictive value, including responsiveness to therapy. In contrast to physical variables, biochemical parameters monitored on a continuous basis are a largely untapped resource because of the lack of clinically usable monitoring systems. This is despite the huge testing repertoire opening up in recent years in relation to discrete biochemical measurements. Electrochemical sensors offer one of the few routes to obtaining continuous readout and, moreover, as implantable devices information referable to specific tissue locations. This review focuses on new biological insights that have been secured through in vivo electrochemical sensors. In addition, the challenges of operating in a reactive, biological, sample matrix are highlighted. Specific attention is given to the choreographed host rejection response, as evidenced in blood and tissue, and how this limits both sensor life time and reliability of operation. Examples will be based around ion, O2, glucose, and lactate sensors, because of the fundamental importance of this group to acute health care

FATHER INVOLVEMENT AMONG ASIAN-INDIAN IMMIGRANTS IN THE UNITED STATES: ACTOR-PARTNER INTERDEPENDENCE MODEL

Parenting is codependent and nested within a familial and cultural structure. While parenting research consistently demonstrates more maternal involvement with children, often fathers’ involvement gets little or no attention. One of the major limitations of fathering research is single source data, often comprised of only mothers’ reports of fathers’ involvement. The purpose of this study was to address this gap by examining the nested nature and interdependence of immigrant parents’ marital adjustment, parenting self-efficacy, and beliefs about parental role and, fathers’ involvement. Actor-partner interdependence model (APIM) was applied to examine the actor (intrapersonal or spillover) and partner (interpersonal or crossover) effects. Data were collected from 127 Asian-Indian immigrant parents of 6 to 10 year old children residing in southern parts of the United States. In the single variable APIMs, actor effect pathways for fathers revealed significant effects of marital adjustment, parenting self-efficacy, and parental role beliefs on fathers’ involvement, but only marital adjustment effect on mothers’ reports of father involvement. These findings indicate that father involvement is enhanced when both fathers’ and mothers’ were adjusted in their marriage, when fathers’ feel efficient in their parenting role and had egalitarian beliefs about parenting. Partner effects were found from mothers’ marital adjustment onto fathers’ reports of involvement. Also, fathers’ parenting self-efficacy significantly influenced mothers’ reports of fathers’ involvement. These partner effects reveal that fathers’ involvement depend on how adjusted mothers were in their marriage, and mothers’ perceptions of fathers’ involvement depend on how efficient fathers were in their parenting role. Keywords: father involvement, immigrants, marital adjustment, parenting self-efficacy, parental role beliefs, and actor-partner interdependence mode

Near infrared spectrometric investigation of lactate in a varying pH buffer

Lactic acidosis is commonly observed in various disease states in critical care and can be adopted as a hemodynamic biomarker, as well as a target for therapy. pH is the main biomarker for the diagnosis of acid–base disorders and is currently measured utilizing invasive blood sampling techniques. Therefore, there is a need for a non-invasive and continuous technology for the measurement of pH and lactate levels. In this work, near infrared spectroscopy is explored as a technique for investigating lactic acidosis. In-vitro studies on 20 isotonic phosphate buffer solutions of varying pH with constant lactate concentration (2 mmol/L) were performed. The whole near infrared spectrum (800–2600 nm) was then divided into four parts for analysis: (a) water absorption peaks, (b) 1000–1250 nm, (c) 1700–1760 nm, and (d) 2200–2400 nm. The water absorption peaks showed a linear variation with the changes in pH in the spectra. The range from 1700–1760 nm showed good correlation with calculated values for lactate ionization, with the changes in pH. However, the region from 2200–2400 nm showed a reverse correlation with respect to the concentration changes of lactate and a distinction could be made from pH 6–7 and 7–8. This study successfully identifies wavelengths (1233 nm, 1710 nm, 1750 nm, 2205 nm, 2319 nm, and 2341 nm) which can be directly correlated to lactic acidosis. Knowledge from this study will contribute toward the development of lactate-based pH monitoring optical sensor for critical care

Microfluidic systems for in situ formation of nylon 6,6 membranes.

A microfluidics based, localised formation of nylon 6,6 membranes has been undertaken. The study demonstrates the feasibility of maintaining stable aqueous/organic interfaces for xylene within simple linear flow channels. Glass fabricated structures were used with adipoyl chloride and hexamethylenediamine in the organic and aqueous phases, respectively, in order to achieve nylon 6,6 interfacial polymerisation. Localised membrane formation was investigated in flow channels of different geometries over a wide range of flow rates (500–4000 μl/min), with Reynolds numbers ranging from 8.4 to 67.2. The results demonstrate that interfacial polymerisation occurs consistently over a wide range of flow rates and of flow entry angles for dual aqueous/organic solvent input. However, creation of uniform planar film structures required careful optimisation, and these were best achieved at 2000 μl/min with a flow entry angle of 45°. The resulting membranes had thicknesses in the range between 100 and 300 μm. Computational modelling of the aqueous/organic flow was performed in order to characterise flow stability and wall shear-stress patterns. The flow arrangement establishes a principle for the fabrication of micromembrane structures designed for low sample volume separation, where the forming reaction is a facile and rapid interfacial process

In vitro quantification of lactate in Phosphate Buffer Saline (PBS) samples.

Continuous measurement of lactate levels in the blood is a prerequisite in intensive care patients who are susceptible to sepsis due to their suppressed immune system and increased metabolic demand. Currently, there exists no noninvasive tool for continuous measurement of lactate in clinical practice. The current mode of measurement is based on arterial blood gas analyzers which require sampling of arterial blood. In this work, we propose the use of Near Infra-Red (NIR) spectroscopy together with multivariate models as a means to non-invasively predict the concentration of lactate in the blood. As the first step towards this objective, we examined the possibility of accurately predicting concentrations of sodium lactate (NaLac) from the NIR spectra of 37 isotonic phosphate buffer saline (PBS) samples containing NaLac ranging from 0 to 20 mmol/L. NIR spectra of PBS samples were collected using the Lambda 1050 dual beam spectrometer over a spectral range of 800 - 2600 nm with a quartz cell of 1 mm optical path. Estimates and calibration of the lactate concentration with the NIR spectra were made using Partial Least-Squares (PLS) regression analysis and leave-one-out cross-validation on filtered spectra. The regression analysis showed a correlation coefficient of 0.977 and a standard error of 0.89 mmol/L between the predicted and prepared samples. The results suggest that NIR spectroscopy together with multivariate models can be a valuable tool for non-invasive assessment of blood lactate concentrations

Antimicrobial, mechanical and thermal studies of silver particle-loaded polyurethane.

Silver-particle-incorporated polyurethane films were evaluated for antimicrobial activity towards two different bacteria: Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Distributed silver particles sourced from silver nitrate, silver lactate and preformed silver nanoparticles were mixed with polyurethane (PU) and variously characterized by field emission scanning electron microscopy (FESEM), fourier transform infra-red (FTIR) spectroscopy, X-ray diffraction (XRD) and contact angle measurement. Antibacterial activity against E.coli was confirmed for films loaded with 10% (w/w) AgNO3, 1% and 10% (w/w) Ag lactate and preformed Ag nanoparticles. All were active against S. aureus, but Ag nanoparticles loaded with PU had a minor effect. The apparent antibacterial performance of Ag lactate-loaded PU is better than other Ag ion-loaded films, revealed from the zone of inhibition study. The better performance of silver lactate-loaded PU was the likely result of a porous PU structure. FESEM and FTIR indicated direct interaction of silver with the PU backbone, and XRD patterns confirmed that face-centred cubic-type silver, representative of Ag metal, was present. Young's modulus, tensile strength and the hardness of silver containing PU films were not adversely affected and possibly marginally increased with silver incorporation. Dynamic mechanical analysis (DMA) indicated greater thermal stability

Near Infrared Spectrometric Investigations on the behaviour of Lactate

In patients with life-threatening illnesses, the metabolic production and disposal of lactate are impaired, which leads to a build-up of blood lactate. In critical care units, the changes in lactate levels are measured through intermittent, invasive, blood sampling and in vitro assay. Continuous monitoring is lacking, yet such monitoring could allow early assessment of severity and prognosis to guide therapy. Currently, there is no routine means to measure lactate levels continuously, particularly non-invasively. The motivation of this study was to understand the interaction of lactate with light in the Near Infra Red (NIR) region of the electromagnetic spectrum. This was to create an opportunity to explore the possibility of a non-invasive sensing technology to monitor lactate continuously. In vitro studies were performed using solution samples with varying concentration levels of sodium lactate in isotonic Phosphate Buffer Solution (PBS) at constant pH (7.4). These samples were prepared using stoichiometric solution compositions and spectra for each sample were taken using a state-of-the-art spectrometer in the NIR region. The spectra were then analysed qualitatively by 2D correlation analysis, which identified the regions of interest. Further analysis of these regions using linear regression at four randomly selected wavelengths showed bathochromic shifts, which, moreover, showed systematic variation correlating with lactate concentration

Comparison of a Genetic Algorithm Variable Selection and Interval Partial Least Squares for quantitative analysis of lactate in PBS

Blood lactate is an important biomarker that has been linked to morbidity and mortality of critically ill patients, acute ischemic stroke, septic shock, lung injuries, insulin resistance in diabetic patients, and cancer. Currently, the clinical measurement of blood lactate is done by collecting intermittent blood samples. Therefore, noninvasive, optical measurement of this significant biomarker would lead to a big leap in healthcare. This study, presents a quantitative analysis of the optical properties of lactate. The benefits of wavelength selection for the development of accurate, robust, and interpretable predictive models have been highlighted in the literature. Additionally, there is an obvious, time- and cost-saving benefit to focusing on narrower segments of the electromagnetic spectrum in practical applications. To this end, a dataset consisting of 47 spectra of Na-lactate and Phosphate Buffer Solution (PBS) was produced using a Fourier transform infrared spectrometer, and subsequently, a comparative study of the application of a genetic algorithm-based wavelength selection and two interval selection methods was carried out. The high accuracy of predictions using the developed models underlines the potential for optical measurement of lactate. Moreover, an interesting finding is the emergence of local features in the proposed genetic algorithm, while, unlike the investigated interval selection methods, no explicit constraints on the locality of features was imposed. Finally, the proposed genetic algorithm suggests the formation of α-hydroxy-esters methyl lactate in the solutions while the other investigated methods fail to indicate this

Comparison of a Genetic Algorithm Variable Selection and Interval Partial Least Squares for quantitative analysis of lactate in PBS

Blood lactate is an important biomarker that has been linked to morbidity and mortality of critically ill patients, acute ischemic stroke, septic shock, lung injuries, insulin resistance in diabetic patients, and cancer. Currently, the clinical measurement of blood lactate is done by collecting intermittent blood samples. Therefore, noninvasive, optical measurement of this significant biomarker would lead to a big leap in healthcare. This study, presents a quantitative analysis of the optical properties of lactate. The benefits of wavelength selection for the development of accurate, robust, and interpretable predictive models have been highlighted in the literature. Additionally, there is an obvious, time- and cost-saving benefit to focusing on narrower segments of the electromagnetic spectrum in practical applications. To this end, a dataset consisting of 47 spectra of Na-lactate and Phosphate Buffer Solution (PBS) was produced using a Fourier transform infrared spectrometer, and subsequently, a comparative study of the application of a genetic algorithm-based wavelength selection and two interval selection methods was carried out. The high accuracy of predictions using the developed models underlines the potential for optical measurement of lactate. Moreover, an interesting finding is the emergence of local features in the proposed genetic algorithm, while, unlike the investigated interval selection methods, no explicit constraints on the locality of features was imposed. Finally, the proposed genetic algorithm suggests the formation of α-hydroxy-esters methyl lactate in the solutions while the other investigated methods fail to indicate this

Investigations into the Effects of pH on Quantitative Measurements of Lactate in Biological Media Using ATR-FTIR Spectroscopy

Quantification of lactate/lactic acid in critical care environments is essential as lactate serves as an important biochemical marker for the adequacy of the haemodynamic circulation in shock and of cell respiration at the onset of sepsis/septic shock. Hence, in this study, ATR-FTIR was explored as a potential tool for lactate measurement, as the current techniques depend on sample preparation and fails to provide rapid response. Moreover, the effects of pH on PBS samples (7.4, 7, 6.5 and 6) and change in solution conditions (PBS to whole blood) on spectral features were also investigated. A total 189 spectra from five sets of lactate containing media were obtained. Results suggests that lactate could be measured with more than 90% accuracy in the wavenumber range of 1500-600 cm-1. The findings of this study further suggest that there exist no effects of change in pH or media, when estimating lactate concentration changes in this range of the Mid-IR spectral region