Blood Plasma Separation Research Articles

Application of Simulation in the Optimization of the Blood Plasma Storage Process

The paper deals with the process of optimizing the creation of the output product, which is the Cobas HIV-1 blood plasma separation card. The capabilities of the Tecnomatix Plant Simulation software will be used in this process. The application of simulation software will help to reveal the possibilities of improvement during the entire production process of the said product and to debug all potential improvement errors on the digital model without physically interfering with the current production process. The paper contains a basic theoretical clarification of some basic terms. The following content describes individual parts of the production process in question. An analysis will be carried out, on the basis of which the most significant bottlenecks will be revealed. The data used to create the simulation were collected based on the recording of working time and its use on the given production line. This kind of observation also revealed initial bottlenecks. For these bottlenecks, a methodology for their effectiveness and criteria for their optimization is subsequently proposed. Subsequently, an optimization solution is proposed, which is verified and evaluated by simulation. The collected data were then transferred to a digital model in the form of a simulation. Based on the results of the simulation, the given optimization proposals will be evaluated at the end. Production on the line has been optimized gradually and thanks to this we can see several variants that can be compared, and the best one can be chosen. The development of the entire optimization process is the possibility to increase the production output from the original 350 produced pieces up to 699 pieces in the same time horizon. In the process of optimization, methodologies were created that followed it and gave instructions for the optimization of productions of a similar nature. In addition to the mentioned optimization simulation variants, the paper also contains a design solution proposal in the form of 3D models, when several workstations are united into one workstation.

Design and Fabrication of a High Performance Microfluidic Chip for Blood Plasma Separation: Modelling and Prediction of System Behaviour via CFD Method.

This paper presents a single-step microfluidic system designed for passive separation of human fresh blood plasma using direct capillary forces. Our microfluidic system is composed of a cylindrical well between upper and lower channel pairs produced by soft photolithography. The microchip was fabricated based on hydrophobicity differences upon suitable cylindrical surfaces using gravitational and capillary forces and lateral migration of plasma and red blood cells. The plasma radiation was applied to attach the polymeric segment (polydimethylsiloxane (PDMS)) to the glass. Meanwhile, Tween 80 was used as a surfactant to increase the hydrophobicity of the lateral channel surfaces. This led to the higher movement of whole blood, including plasma. Fick's law of diffusion was validated for this diffusion transfer, the Navier-Stokes equation was used for the momentum balance, and the Laplace equation was utilized for the dynamics of the mesh. A model with high accuracy using the COMSOL Multiphysics software was created to predict the capillary forces and chip model validation. RBCs (red blood cells) were measured by the H3 cell counter instrument, by which 99% plasma purity was achieved. Practically, 58.3% of the plasma was separated from the blood within 12 min. Correlation between plasma separation results obtained from software and experimental data showed a coefficient of determination equal to 0.9732. This simple, rapid, stable, and reliable microchip can be considered as a promising candidate for providing plasma in point-of-care diagnostics.

A theoretical framework to determine the optimal centrifugation angle for separation of plasma from blood samples

The separation of blood plasma by centrifugation can be accelerated by placement of the sample at an angle relative to the direction of the centrifugal force. This geometric effect, which has been known for a century, is due to the Boycott effect, while the enhanced sedimentation of red blood cells (RBCs) in tilted vessels can be attributed to buoyancy-induced convection. Moreover, flow instability would invalidate the traditional predictive model and weaken separation enhancement. While current model considers only the geometric effect, by considering the buoyancy-induced convection and flow instability, we devise a model for the first time enabling the prediction of the optimal tilt angle to achieve the highest separation efficiency. A comparison of our theoretical prediction with the available experimental data shows good agreement. A sensitivity analysis is also conducted to investigate the influence of variation in blood samples on the physical parameters.

Integrating Bio-Sensing Array with Blood Plasma Separation on a Centrifugal Platform.

Numerous immunoassays have been successfully integrated on disc-based centrifugal platforms (CDs) over the last 20 years. These CD devices can be used as portable point-of-care (POC) platforms with sample-to-answer capabilities where bodily fluids such as whole blood can be used as samples directly without pre-processing. In order to use whole blood as a sample on CDs, centrifugation is used to separate red blood cells from plasma on CDs. There are several techniques for using specific fluidic patterns in the centrifugal fluidic network, such as reciprocation, that enhances the sensitivity of the immunoassays, including those using microarray antigen membranes. Present work demonstrates, for the first time, simultaneous integration of blood plasma separation (BPS) and reciprocation on the CD platform. The integrated design allows plasma that is separated from the red blood cells in a sedimentation chamber to flow into the reciprocation chamber via a narrow connecting channel of 0.5 mm × 0.5 mm cross-section. Due to the small cross-section of the connecting channel, there is no inflow of the red blood cell into the reciprocation chamber during subsequent fluidic operations of the CD. While no inflow of the red blood cells into the reciprocation chamber was observed, the conditions of 20 g jerk acceleration were also simulated in ANSYS finite element analysis software, and it was found that the CD design that was used is capable of retaining red blood cells in the sedimentation chamber. Experimentally, the isolation of red blood cells in the sedimentation chamber was confirmed using the ImageJ image processor to detect the visible color-based separation of the plasma from the blood. A fluorescent analyte testing on the bio-sensing array of the presented novel integrated design and on the standard reciprocation design CD was conducted for 7 min of reciprocation in each case. The test analyte was Europium Streptavidin Polystyrene analyte (10-3 mg/mL) and the microarray consisted of Biotin bovine serum albumin (BSA) dots. The fluorescent signals for the standard and integrated designs were nearly identical (within the margin of error) for the first several minutes of reciprocation, but the fluorescent signal for the integrated design was significantly higher when the reciprocation time was increased to 7 min.

A capillary flow-driven microfluidic device for point-of-care blood plasma separation

Plasma has significant utility as an input for diagnostics and screening for conditions such as viral infections, cancer, and more. However, plasma is difficult to obtain at the point-of-care, as separation from whole blood is typically carried out via centrifugation. We have designed and optimized a low-cost, simple-to-operate microfluidic device which carries out the separation of plasma from whole blood. The device utilizes depth filtration as its separation mechanism and collects plasma via capillary action, allowing for operation without components that drive flow externally. We first optimized device dimensions and operating parameters and demonstrated consistent separation efficiencies for the samples with hematocrits ranging from 25–65%. The impact of input sample hematocrit percentage on flow rate through the device was also examined, with samples with hematocrits greater than 45% decreasing plasma flow rate. Lastly, we evaluated the ability of this device to produce plasma with a high protein concentration and found no significant difference between protein levels in samples from the device compared to samples produced via centrifugation. This system produced plasma with a maximum separation efficiency of 88.5% and achieved a maximum plasma volume of ∼14 μl from a 50 μl whole blood input. The low cost, simplicity of operation, and high plasma quality associated with this device give it many advantages in a point-of-care setting. This device could be integrated into plasma-based diagnostic workflows to increase access to various types of disease testing and monitoring.

Extremely Precise Blood-Plasma Separation from Whole Blood on a Centrifugal Microfluidic Disk (Lab-on-a-Disk) Using Separator Gel.

Due to the expansion of point-of-care devices, proposing a convenient and efficient method for blood-plasma separation would help with the use of point-of-care devices. Commercial microfluidic chips are only able to separate a limited amount of plasma, and the majority of these chips need an active valve system, which leads to increase manufacturing cost and complexity. In this research study, we designed a centrifugal microfluidic disk with a passive valve for ultra-accurate and efficient blood-plasma separation on a large scale (2-3 mL). The disk contained a separator gel, which, after applying the centrifugal force, separated the plasma and red blood cells. The passive valve worked based on the inertial force and was able to transfer more than 90% of the separated plasma to the next chamber. The results demonstrated that the separated plasma was 99.992% pure. This study compared the efficiency of the disk containing separating gel with the common lab-on-a-disk design for plasma separation. A comparison of the results showed that although the common lab-on-a-disk design could separate almost pure plasma as the disk contained separator gel, it could only transfer 60% of plasma to the next chamber.

A microfluidic device to separate high-quality plasma from undiluted whole blood sample using an enhanced gravitational sedimentation mechanism

The growing interest in lab-on-a-chip systems for plasma separation has led to the presentation of various devices. Trench-based devices benefiting from gravitational sedimentation are efficient structures with air-locking and low speed-drawbacks. The present study introduces a fast, hemolysis-free, highly efficient blood plasma separation microfluidic device. The proposed device is based on gravitational sedimentation combined with dielectrophoresis force to promote the purity of the separated plasma, reduce the separation process time, and overcome the air-locking problem. The effect of geometrical parameters on the separation process is investigated using finite element analysis to attain optimal design specifications. A drop of whole blood (10 μl) is injected into the fabricated chip at four flow rates of 70 nl/s to 100 nl/s. It takes less than 4 min to obtain 2.2 μl plasma from undiluted blood without losing plasma proteins. Additionally, a porous Melt-Blown Polypropylene (MBPP) layer is used to eliminate the air-locking problem, which in previous trench-based microsystems led to time-consuming device preparation steps. Blood samples with various hematocrits (15%–65%) are tested with the applied voltages of 0–20 Vpp through the optimized structure. A purity of 99.98% ± 0.02% (evaluated by hemocytometry) is achieved using optimized dielectrophoresis force by the applied voltage of 20 Vpp, which is more than the previous studies. The UV–Visible spectroscopy results confirm obtaining a non-hemolyzed sample at a flow rate of 70 nl/s. The proposed device achieves a relative increase in the flow rate compared to similar previous studies while maintaining the high quality of the separated plasma. This achievement lies in using the MBPP layer and combining two separation methods.

Microvalves for Applications in Centrifugal Microfluidics.

Centrifugal microfluidic platforms (CDs) have opened new possibilities for inexpensive point-of-care (POC) diagnostics. They are now widely used in applications requiring polymerase chain reaction steps, blood plasma separation, serial dilutions, and many other diagnostic processes. CD microfluidic devices allow a variety of complex processes to transfer onto the small disc platform that previously were carried out by individual expensive laboratory equipment requiring trained personnel. The portability, ease of operation, integration, and robustness of the CD fluidic platforms requires simple, reliable, and scalable designs to control the flow of fluids. Valves play a vital role in opening/closing of microfluidic channels to enable a precise control of the flow of fluids on a centrifugal platform. Valving systems are also critical in isolating chambers from the rest of a fluidic network at required times, in effectively directing the reagents to the target location, in serial dilutions, and in integration of multiple other processes on a single CD. In this paper, we review the various available fluidic valving systems, discuss their working principles, and evaluate their compatibility with CD fluidic platforms. We categorize the presented valving systems into either "active", "passive", or "hybrid"-based on their actuation mechanism that can be mechanical, thermal, hydrophobic/hydrophilic, solubility-based, phase-change, and others. Important topics such as their actuation mechanism, governing physics, variability of performance, necessary disc spin rate for valve actuation, valve response time, and other parameters are discussed. The applicability of some types of valves for specialized functions such as reagent storage, flow control, and other applications is summarized.

Microfluidics geometries involved in effective blood plasma separation.

The last two decades witnessed a significant advancement in the field of diluted and whole blood plasma separation. This is one of the common procedures used to diagnose, cure and treat numerous acute and chronic diseases. For this separation purpose, various types of geometries of microfluidic devices, such as T-channel, Y-channel, trifurcation, constriction–expansion, curved/bend/spiral channels, a combination of any of the two geometries, etc., are being exploited, and this is detailed in this review article. The evaluation of the performance of such devices is based on the several parameters such as separation efficiency, flow rate, hematocrits, channel dimensions, etc. Thus, the current extensive review article endeavours to understand how particular geometry influences the separation efficiency for a given hematocrit. Additionally, a comparative analysis of various geometries is presented to demonstrate the less explored geometric configuration for the diluted and whole blood plasma separation. Also, a meta-analysis has been performed to highlight which geometry serves best to give a consistent separation efficiency. This article also presents tabulated data for various geometries with necessary details required from a designer’s perspective such as channel dimensions, targeted component, studied range of hematocrit and flow rate, separation efficiency, etc. The maximum separation efficiency that can be achieved for a given hematocrits and geometry has also been plotted. The current review highlights the critical findings relevant to this field, state of the art understanding and the future challenges.

A low-cost, open-source centrifuge adaptor for separating large volume clinical blood samples.

Blood plasma separation is a prerequisite in numerous biomedical assays involving low abundance plasma-borne biomarkers and thus is the fundamental step before many bioanalytical steps. High-capacity refrigerated centrifuges, which have the advantage of handling large volumes of blood samples, are widely utilized, but they are bulky, non-transportable, and prohibitively expensive for low-resource settings, with prices starting at $1,500. On the other hand, there are low-cost commercial and open-source micro-centrifuges available, but they are incapable of handling typical clinical amounts of blood samples (2-10mL). There is currently no low-cost CE marked centrifuge that can process large volumes of clinical blood samples on the market. As a solution, we customised the rotor of a commercially available low-cost micro-centrifuge (~$125) using 3D printing to enable centrifugation of large clinical blood samples in resource poor-settings. Our custom adaptor ($15) can hold two 9 mL S-Monovette tubes and achieve the same separation performance (yield, cell count, hemolysis, albumin levels) as the control benchtop refrigerated centrifuge, and even outperformed the control in platelet separation by at least four times. This low-cost open-source centrifugation system capable of processing clinical blood tubes could be valuable to low-resource settings where centrifugation is required immediately after blood withdrawal for further testing.

Smartphone-based automated estimation of plasma creatinine from finger-pricked blood on a paper strip via single-user step sample-to-result integration

Measuring creatininelevels in blood plasma is one of the most commonly used means of routine monitoring of renal function. Point-of-care devicesfor creatinine level estimation potentially allow rapid measurement, facilitating continuous monitoring of vulnerable patients. However, a majority of such devices currently available is constrained by several factors such as lack of simplicity in fabrication and operation (including plasma separation), a limited regime of efficacy, compromised reagent stability, and elevated costs. Here, we report the invention of a simple-to-fabricate and easy-to-use paper strip for rapid evaluation of plasma creatinine levels (ranging from 0.1 to 15 mg dL-1) in an integrated single-step process. For the testing, one drop of whole blood is first dripped onto the calcium salt-functionalized sample pad of the strip. Subsequently, blood plasma separation occurs due to spontaneous aggregation of red blood cells (RBCs) in the presence of calcium ions. The plasma spontaneously traverses into the reaction zone of the test-strip via capillary action where it reacts with previously dispensed alkaline picrate reagent, resulting in a colorimetric signal. Smartphone-interfaced imaging and image analytics of the reaction spot renders the dissemination of the test result in a turn-around time of about 2–3 min, without necessitating additional device interfacing. High efficacy of performance is established by validating with the results obtained from laboratory-benchmarked biochemical auto-analyzer, exhibiting an accuracy of 94%, and the coefficient of variation ranging from 0.64 to 6.4%. Suitability of use in extreme resource-limited settings is established by favorable stability of the reagents outside controlled laboratory ambience and engagement of unskilled personnel to execute the testing procedure with uncompromised accuracy.

A self-pressure-driven blood plasma-separation device for point-of-care diagnostics

We aimed to develop a portable, simple-to-use, and self-pressure-driven blood plasma-separation device that can be combined with rapid diagnostic test kits. This simple, disposable, and electrical equipment-free apparatus has been designed to separate plasma from a few microliters of blood with only hand-powered operation. The refined plasma sample is then delivered to multiple lateral flow assay kits directly connected to the device for the detection of various serological markers. The required time for all steps was just 1 min. We validated the device through multifaceted experiments. The developed multifunctional device enables to perform all blood test steps of diagnostic medical examination at the point-of-care.

Microfluidic Paper-Based Blood Plasma Separation Device as a Potential Tool for Timely Detection of Protein Biomarkers.

A current challenge regarding microfluidic paper-based analytical devices (µPAD) for blood plasma separation (BPS) and electrochemical immunodetection of protein biomarkers is how to achieve a µPAD that yields enough plasma to retain the biomarker for affinity biosensing in a functionalized electrode system. This paper describes the development of a BPS µPAD to detect and quantify the S100B biomarker from peripheral whole blood. The device uses NaCl functionalized VF2 filter paper as a sample collection pad, an MF1 filter paper for plasma retention, and an optimized microfluidic channel geometry. An inverted light microscope, scanning electron microscope (SEM), and image processing software were used for visualizing BPS efficiency. A design of experiments (DOE) assessed the device’s efficacy using an S100B ELISA Kit to measure clinically relevant S100B concentrations in plasma. The BPS device obtained 50 μL of plasma from 300 μL of whole blood after 3.5 min. The statistical correlation of S100B concentrations obtained using plasma from standard centrifugation and the BPS device was 0.98. The BPS device provides a simple manufacturing protocol, short fabrication time, and is capable of S100B detection using ELISA, making one step towards the integration of technologies aimed at low-cost POC testing of clinically relevant biomarkers.

Optimization of injection molded polymer lab-on-a-chip for acoustic blood plasma separation using virtual design of experiment

This study presents the development towards the optimization and manufacturing of a novel cost-effective fully polymer-based ultrasound actuated chip as a Point-of-care (POC) diagnostic platform for blood plasma separation and analysis. The chip was designed following multi-physic functional simulation to obtain optimal dimensions with respect to blood separation enhanced capacity. Initial dimensional guidelines showed most favorable performance to be achieved with design dimensions of 150 µm height, 375 µm width and 34 mm length. The chip encompasses a micro-fluidic channel with a relatively long length compared to the height and the width. As such, main manufacturability challenge is represented by the capability to maintain the channel dimensional conformance throughout the entire length. In order to tackle the challenge and optimize the results, developing a feedback loop was initiated for the device process development where the data of the preliminary micro-injection molding (µIM) production was exploited to implement a simulation-based full-factorial virtual design of experiment (DOE) for all the four materials of interest: polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), polycarbonate (PC) and polystyrene (PS). The four essential µIM parameters namely, mold temperature, melt temperature, injection velocity and packing pressure were used as factors. Overall, simulations were performed based on the virtual DOE inputs for the four aforementioned materials. The input data for the utilized process parameters in the virtual DOE was provided by our first production batch. Ultimately, in the case of PMMA, parts were molded and characterized based on the process settings that had demonstrated the lowest linear shrinkage in our entire virtual DOE responses. For the linear shrinkage of these parts, a respective width and height difference of 1% and 3.3% between the simulations and production results were obtained. Moreover, as a secondary study sink marks were also inspected and minimized through simulations. Initially, sink marks as deep as 80 µm were spotted on the chip. After the use of optimization cycle the value decreased to as low as 10 µm. The results confirm the positive impact of the virtual experiments for future rapid assessment of potential new chip designs.

High-performance blood plasma separation based on a Janus membrane technique and RBC agglutination reaction.

Separation of plasma which is full of various biomarkers is critical for clinical diagnosis. However, the point-of-care plasma separation often relies on microfluidic filtration membranes which are usually limited in purity, yield, hemolysis, extraction speed, hematocrit level, and protein recovery. Here, we have developed a high-performance plasma membrane separation technique based on a Janus membrane and red blood cell (RBC) agglutination reaction. The RBC agglutination reaction can form larger RBC aggregates to separate plasma from blood cells. Then, the Janus membrane, serving as a multipore microfilter to block large RBC aggregates, allows the plasma to flow from the hydrophobic side to its hydrophilic side spontaneously. As a result, the separation technique can extract highly-purified plasma (99.99%) from whole blood with an ultra-high plasma yield (∼80%) in ∼80 s. Additionally, the separation technique is independent of the hematocrit level and can avoid hemolysis.

A circular gradient-width crossflow microfluidic platform for high-efficiency blood plasma separation

Separation and collection of blood plasma are required steps for broad ranges of clinical diagnostic assays. Here, we introduce a continuous-flow blood plasma separation microfluidic device based on size exclusion cell separation in crossflow microchannels. A gradient-width crossflow microchannel structure is utilized to minimize blood cell leakage into the plasma collection channel while maximizing the flow rate for higher throughput. Additionally, the crossflow channels are placed at the corner of the blood channel to enhance Fahraeus effects, resulting in reduction of the concentration of blood cells around the entrance of the crossflow channels. Combined with a circular geometry that minimizes the footprint of the device for point-of-care diagnosis applications, the developed device significantly improves the performance of blood plasma separation in terms of separation efficiency, degree of hemolysis, and microchannel clogging by blood cells. At a relatively high flow rate of 2000 µl/h for a passive blood separation device, a plasma extraction ratio of 22% and red blood cell separation efficiency of 97% could be achieved using undiluted whole human blood, where such separation efficiency is about 28% higher compared with that of a conventional crossflow design. The effect of channel height and flow rate on the degree of hemolysis was also investigated, where the optimized device could achieve very little hemolysis (0.01–0.5%), demonstrating that the device can produce high-quality blood plasma. Integration of this high-performance, compact, and passive blood plasma separation microdevice with on-chip blood biomarker sensing elements can create a point-of-care diagnosis system with reduced cost, test time, and sample/reagent volume.

Microfluidic thread-based analytical devices for point-of-care detection of therapeutic antibody in blood

In therapies involving therapeutic antibodies, therapeutic drug monitoring (TDM) has the potential to substantially increase clinical efficacy and to enable more economical drug use, because the clearance from the bloodstream after administration is patient dependent. Since TDM must be performed continuously and over extended time periods, it should ideally be achieved through an economical and easy to perform point-of-care (POC) assay. Here, we introduce a new analytical method for POC TDM of the clinically important therapeutic antibody cetuximab, using microfluidic thread-based analytical devices (µTADs) as a platform for a bioluminescence resonance energy-transfer (BRET) switching sensor protein for simple quantitative antibody detection. The µTAD is pre-treated with NaCl for blood plasma separation and a BRET switching sensor protein and its substrate for cetuximab detection, integrating all elements required for a reagent-free, single-step assay. A change in bioluminescence emission color depending on cetuximab concentrations occurs after whole blood application. The device design enables the quantification of cetuximab within the therapeutically relevant blood concentration range in 2.5 min using only 2 µL of whole blood. The results obtained are independent of the blood volume. This µTAD can be stored for about one month at − 20 °C, a temperature compatible with commonly available freezers. The application of mathematical morphology recognition (MMR)-integrated image processing techniques for the automatic selection of regions of interest (ROIs) yields results with minimal error. The simplicity of use, rapidity, and cost-effectiveness of this µTAD are expected to offer the possibility of achieving TDM of therapeutic antibodies at POC for individual patients.

Sub-Minute Analysis of Lactate from a Single Blood Drop Using Capillary Electrophoresis with Contactless Conductivity Detection in Monitoring of Athlete Performance.

A simple and fast method for the analysis of lactate from a single drop of blood was developed. The finger-prick whole blood sample (10 µL) was diluted (1:20) with a 7% (w/v) solution of [tris(hydroxymethyl)methylamino] propanesulfonic acid and applied to a blood plasma separation device. The device accommodates a membrane sandwich composed of an asymmetric polysulfone membrane and a supporting textile membrane that allows the collection of blood plasma into a narrow glass capillary in less than 20 s. Separated and simultaneously diluted blood plasma was directly injected into a capillary electrophoresis instrument with a contactless conductivity detector (CE-C4D) and analyzed in less than one minute. A separation electrolyte consisted of 10 mmol/L l-histidine, 15 mmol/L dl-glutamic acid, and 30 µmol/L cetyltrimethylammonium bromide. The whole procedure starting from the finger-prick sampling until the CE-C4D analysis was finished, took less than 5 min and was suitable for monitoring lactate increase in blood plasma during incremental cycling exercise. The observed lactate increase during the experiments measured by the developed CE-C4D method correlated well with the results from a hand-held lactate analyzer (R = 0.9882). The advantage of the developed CE method is the speed, significant savings per analysis, and the possibility to analyze other compounds from blood plasma.

High-Performance Passive Plasma Separation on OSTE Pillar Forest.

Plasma separation is of high interest for lateral flow tests using whole blood as sample liquids. Here, we built a passive microfluidic device for plasma separation with high performance. This device was made by blood filtration membrane and off-stoichiometry thiol–ene (OSTE) pillar forest. OSTE pillar forest was fabricated by double replica moldings of a laser-cut polymethylmethacrylate (PMMA) mold, which has a uniform microstructure. This device utilized a filtration membrane to separate plasma from whole blood samples and used hydrophilic OSTE pillar forest as the capillary pump to propel the plasma. The device can be used to separate blood plasma with high purity for later use in lateral flow tests. The device can process 45 L of whole blood in 72 s and achieves a plasma separation yield as high as 60.0%. The protein recovery rate of separated plasma is 85.5%, which is on par with state-of-the-art technologies. This device can be further developed into lateral flow tests for biomarker detection in whole blood.

Engineered Membranes for Residual Cell Trapping on Microfluidic Blood Plasma Separation Systems: A Comparison between Porous and Nanofibrous Membranes.

Blood-based clinical diagnostics require challenging limit-of-detection for low abundance, circulating molecules in plasma. Micro-scale blood plasma separation (BPS) has achieved remarkable results in terms of plasma yield or purity, but rarely achieving both at the same time. Here, we proposed the first use of electrospun polylactic-acid (PLA) membranes as filters to remove residual cell population from continuous hydrodynamic-BPS devices. The membranes hydrophilicity was improved by adopting a wet chemistry approach via surface aminolysis as demonstrated through Fourier Transform Infrared Spectroscopy and Water Contact Angle analysis. The usability of PLA-membranes was assessed through degradation measurements at extreme pH values. Plasma purity and hemolysis were evaluated on plasma samples with residual red blood cell content (1, 3, 5% hematocrit) corresponding to output from existing hydrodynamic BPS systems. Commercially available membranes for BPS were used as benchmark. Results highlighted that the electrospun membranes are suitable for downstream residual cell removal from blood, permitting the collection of up to 2 mL of pure and low-hemolyzed plasma. Fluorometric DNA quantification revealed that electrospun membranes did not significantly affect the concentration of circulating DNA. PLA-based electrospun membranes can be combined with hydrodynamic BPS in order to achieve high volume plasma separation at over 99% plasma purity.