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

What can we learn from senescent platelets, their transcriptomes and proteomes?

Research into the natural aging process of platelets has garnered much research interest in recent years, and there have long been associations drawn between the proportion of newly formed platelets in the circulation and the risk of thrombosis. However, these observations have largely been demonstrated in patient groups in which there may be underlying systemic changes that effect platelet function. Recent advances in technology have allowed in-depth analysis of differently aged platelets isolated from the peripheral blood of healthy individuals and have demonstrated that aged platelets, often referred to as senescent platelets, undergo extensive changes in the transcriptome and proteome. Ultimately, these changes result in platelets whose functions have deteriorated such that they cannot partake in hemostatic responses to the same extent as newly formed platelets. Here, we review transcriptomic and proteomic research in platelet aging in the context of health and how this research sheds light upon alterations in platelet structure and function

Platelet ageing: A review.

Platelet ageing is an area of research which has gained much interest in recent years. Newly formed platelets, often referred to as reticulated platelets, young platelets or immature platelets, are defined as RNA-enriched and have long been thought to be hyper-reactive. This latter view is largely rooted in associations and observations in patient groups with shortened platelet half-lives who often present with increased proportions of newly formed platelets. Evidence from such groups suggests that an increased proportion of newly formed platelets is associated with an increased risk of thrombotic events and a reduced effectiveness of standard anti-platelet therapies. Whilst research has highlighted the existence of platelet subpopulations based on function, size and age within patient groups, the common intrinsic changes which occur as platelets age within the circulation are only just being explored. By understanding the changes that occur during the natural ageing processes of platelets, we may be able to identify the triggers for alterations in platelet life span and platelet reactivity. Here we review research on platelet ageing in the context of health and disease, paying particular attention to the experimental approaches taken and the robustness of conclusions that can be drawn

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

Near Infrared and Aquaphotomic analysis of water absorption in lactate containing media

Increased concentrations of lactate levels in blood are often seen in patients with life-threatening cellular hypoperfusion or infections. State-of-the-art techniques used in clinical practice for measuring serum lactate concentrations rely on intermittent blood sampling and do not permit continuous monitoring of this all important parameter in critical care environments.In recent years, Near Infrared (NIR) Spectroscopy has been established as a possible alternative to existing methods that can mitigate these constraints and be used for non-invasive continuous monitoring of lactate. Nevertheless, the dominant absorption of -OH overtone bands of water in the NIR presents a challenge and complicates the accurate detection of other absorbers such as lactate. For this reason, comprehensive analysis of the -OH overtone bands with systematic lactate concentration changes is essential. This paper reports on the analysis of NIR spectra of two aqueous systems of varying concentrations of lactate in saline and whole blood using the principles of Aquaphotomics.The results show distinctive conformational and structural differences in lactate-water binding, which arise due to the molecular interactions of bonds present in respective solvents

Identification and Quantitative Determination of Lactate Using Optical Spectroscopy—Towards a Noninvasive Tool for Early Recognition of Sepsis

Uninterrupted monitoring of serum lactate levels is a prerequisite in the critical care of patients prone to sepsis, cardiogenic shock, cardiac arrest, or severe lung disease. Yet there exists no device to continuously measure blood lactate in clinical practice. Optical spectroscopy together with multivariate analysis is proposed as a viable noninvasive tool for estimation of lactate in blood. As an initial step towards this goal, we inspected the plausibility of predicting the concentration of sodium lactate (NaLac) from the UV/visible, near-infrared (NIR), and mid-infrared (MIR) spectra of 37 isotonic phosphate-buffered saline (PBS) samples containing NaLac ranging from 0 to 20 mmol/L. UV/visible (300–800 nm) and NIR (800–2600 nm) spectra of PBS samples were collected using the PerkinElmer Lambda 1050 dual-beam spectrophotometer, while MIR (4000–500 cm−1) spectra were collected using the Spectrum two FTIR spectrometer. Absorption bands in the spectra of all three regions were identified and functional groups were assigned. The concentration of lactate in samples was predicted using the Partial Least-Squares (PLS) regression analysis and leave-one-out cross-validation. The regression analysis showed a correlation coefficient (R2) of 0.926, 0.977, and 0.992 for UV/visible, NIR, and MIR spectra, respectively, between the predicted and reference samples. The RMSECV of UV/visible, NIR, and MIR spectra was 1.59, 0.89, and 0.49 mmol/L, respectively. The results indicate that optical spectroscopy together with multivariate models can achieve a superior technique in assessing lactate concentrations

Monitoring of lactate in interstitial fluid, saliva and sweat by electrochemical biosensor: the uncertainties of biological interpretation

Lactate electrochemical biosensors were fabricated using Pediococcus sp lactate oxidase (E.C. 1.1.3.2), an external polyurethane membrane laminate diffusion barrier and an internal ionomeric polymer barrier (sulphonated polyether ether sulphone polyether sulphone, SPEES PES). In a needle embodiment, a Pt wire working electrode was retained within stainless steel tubing serving as pseudoreference. The construct gave linearity to at least 25 mM lactate with 0.17 nA/mM lactate sensitivity. A low permeability inner membrane was also unexpectedly able to increase linearity. Responses were oxygen dependent at pO2 < 70 mmHg, irrespective of the inclusion of an external diffusion barrier membrane. Subcutaneous tissue was monitored in Sprague Dawley rats, and saliva and sweat during exercise in human subjects. The tissue sensors registered no response to intravenous Na lactate, indicating a blood-tissue lactate barrier. Salivary lactate allowed tracking of blood lactate during exercise, but lactate levels were substantially lower than those in blood (0–3.5 mM vs. 1.6–12.1 mM), with variable degrees of lactate partitioning from blood, evident both between subjects and at different exercise time points. Sweat lactate during exercise measured up to 23 mM but showed highly inconsistent change as exercise progressed. We conclude that neither tissue interstitial fluid nor sweat are usable as surrogates for blood lactate, and that major reappraisal of lactate sensor use is indicated for any extravascular monitoring strategy for lactate