Multiplexed quantification of proteins adsorbed to surface-modified and non-modified microdialysis membranes

Micro-dialysis has been established in the clinical environment for continuously harvesting body fluids, but a drawback of this process are variable recovery rates, which can be observed especially for subcutaneously implanted catheters. Perfusates with either acetate or mannitol have been investigated as recovery markers. The latter substance is suggested for application with external cavity tuneable quantum cascade lasers, rendering a limited wavenumber interval in contrast to FTIR-spectrometers. Despite the overlap of mannitol and glucose spectra, their simultaneous quantification was successful. By investigating the depletion of the marker substances from the perfusates using different micro-dialysis devices, the theoretical nonlinear relationship between the relative dialysate marker concentration and glucose recovery rate was confirmed for the marker substance-analyte pair of acetate and glucose, rendering a basis for reliable blood glucose measurements. For the pair of mannitol and glucose an almost linear dependency was expected for the microdialysate catheters and experimentally verified, which provides a straightforward correction of any dialysis recovery rate variation during patient monitoring.

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“…An investigation into the quantification of proteins adsorbed onto microdialysis membranes has been published recently. 28 …”

Section: Modeling Diffusion Processes Across Microdialysis Membranes mentioning

confidence: 99%

Ex-vivo glucose sensors using micro-dialysis: importance of on-line recovery rate determination by multi-analyte infrared spectrometry

et al. 2015

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“…23,24 To reduce and control the protein adsorption while retaining the performance of the microdialysis catheter, new methods (tri-block copolymer Poloxamer 407 surface-modified microdialysis) are currently being investigated in vitro, and show great potential for studying complex protein adsorption systems. 25 Samples (150 lL volume) were analyzed with the CMA 600 Microdialysis Analyzer (CMA/Microdialysis, Sweden). CSF and ECF dialysate were analyzed with high performance liquid chromatography-mass spectrometry (HPLC-MS).…”

Section: Assay Methodsmentioning

confidence: 99%

Exposure of Cyclosporin A in Whole Blood, Cerebral Spinal Fluid, and Brain Extracellular Fluid Dialysate in Adults with Traumatic Brain Injury

Brophy

Mazzeo

Brar

et al. 2013

Journal of Neurotrauma

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Cyclosporin A (CsA), an immunosuppressive medication traditionally used in the prevention of post-transplant rejection, is a promising neuroprotective agent for traumatic brain injury (TBI). Preliminary studies in animals and humans describe the efficacy and safety of CsA when administered following neurotrauma. The objective of this study is to describe CsA exposure in adults with severe TBI by assessing concentrations in whole blood, cerebrospinal fluid (CSF), and brain extracellular fluid (ECF) dialysate as measured by brain microdialysis. Severe TBI patients were enrolled in a randomized controlled trial following the written informed consent of their legal guardians. Patients received either CsA 5 mg/kg as a continuous infusion over 24 h, or matching placebo. Noncompartmental exposure analyses were performed using CsA concentrations in whole blood, CSF, and ECF dialysate. There were 37 patients randomized to the CsA arm of the trial and included in this exposure analysis. CsA was detected in the ECF dialysate and CSF at a fraction of the whole blood concentration. Mean CsA maximum concentrations were achieved at 24 and 30 h from the start of the 24 h infusion, in the CSF and ECF dialysate, respectively. A correlation was found between ECF dialysate and CSF concentrations. CsA was detected in the blood, CSF, and brain ECF dialysate. CsA exposure characteristic differences exist for whole blood, CSF, and ECF dialysate in severe TBI patients when administered as a continuous intravenous infusion. These exposure characteristics should be used for safer CsA dose optimization to achieve target CsA concentrations for neuroprotection in future TBI studies.

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“…In alignment with previous studies (Dahlin et al 2010;, the Poloxamer 407 modified catheters have higher FR-precision compared to the native catheters. Based on the theory in the study by Dahlin et al (2012), the Poloxamer 407 coating will alter the pore and membrane surface structure, from which the consequence may be an increased membrane resistance. An increased membrane resistance leads to a lower slope value in the linear function between FR and chamber pressure (Eq.…”

Section: Fluid Recovery As a Function Of Pressure And Surface Modificmentioning

confidence: 99%

“…The Poloxamer 407 coated MD-membranes adsorbed 33% less proteins than membranes without coating (Dahlin et al 2012). The coating has shown to increase the FR precision both in vitro (Dahlin et al 2010) and in vivo .…”

Section: Introductionmentioning

confidence: 98%

Influence of surface modification and static pressure on microdialysis protein extraction efficiency

Chu

Undin

Lind

et al. 2015

Biomed Microdevices

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Influence of surface modification and static pressure on microdialysis protein extractionefficiency. Biomedical microdevices (Print)http://dx.doi.org/10.1007/s10544-015-0005-3Access to the published version may require subscription. N.B. When citing this work, cite the original published paper. ABSTRACTThere is growing interest in using microdialysis (MD) for monitoring larger and more complex molecules such as neuropeptides and proteins. This promotes the use of MD membranes with molecular weight cut off (MWCO) of 100 kDa or above. The hydrodynamic property of the membrane goes to ultrafiltration or beyond, making the MD catheters more sensitive to pressure.In the meantime, despite the large pore size, studies have shown that membrane biofouling still lead to unstable catheter performance. The objective is to study in vitro how 500 kDa dextran and Poloxamer 407 surface modification affect the fluid recovery (FR) and extraction efficiency (EE) of 100 kDa MWCO MD catheters. A pressure chamber was designed to facilitate the tests, using as MD sample a protein standard with similar concentrations as in human cerebral spinal fluid, comparing native and Poloxamer 407 modified MD catheters. The collected dialysate fractions were examined for FR and protein EE, employing Dot-it Spot-it Protein Assay for total protein EE and targeted mass spectrometry (MS) for EE of individual proteins and peptides. The FR results suggested that the surface modified catheters were less sensitive to the pressure and provide higher precision, and provided a FR closer to 100%. The surface modification did not show a significant effect on the protein EE. The average total protein EE of surface modified catheters was slightly higher than that of the native ones. The MS EE data of individual proteins showed a clear trend of complex response in EE with pressure.

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Multiplexed quantification of proteins adsorbed to surface-modified and non-modified microdialysis membranes

Cited by 37 publications

References 23 publications

Ex-vivo glucose sensors using micro-dialysis: importance of on-line recovery rate determination by multi-analyte infrared spectrometry

Ex-vivo glucose sensors using micro-dialysis: importance of on-line recovery rate determination by multi-analyte infrared spectrometry

Exposure of Cyclosporin A in Whole Blood, Cerebral Spinal Fluid, and Brain Extracellular Fluid Dialysate in Adults with Traumatic Brain Injury

Influence of surface modification and static pressure on microdialysis protein extraction efficiency

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