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- Dobielewski, Mikolaj, et al.
(författare)
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Blood Cell Quantification on Dry Blood Samples - Towards Patient-CentricComplete Blood Counts (CBC)
- 2022
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Ingår i: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Performing complete blood counts (CBC) from patients´ homes could have atransformative impact on e-based healthcare. Blood microsampling and sample drying are enablingelements for patient-centric healthcare. The aim of this study is to investigate the potential of dry bloodsamples for image-based cell quantification of red and white blood cells. Methods: A manual samplepreparation method is developed and tested for image-based red and white blood cell counting. Resultsand Conclusion: Dry blood samples enable image-based cell counting of red and white blood cells with agood correlation to gold standard hematology analyzer data (avg. CV < 6.5%, R2 > 0.8), and resolve thebasic morphology of white blood cell nuclei. The presented proof-of-principle study is a first step towardpatient-centric CBCs.
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2. |
- Hauser, Janosch, et al.
(författare)
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A blood hematocrit test strip
- 2019
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Ingår i: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - : IEEE. - 9781728116105 ; , s. 426-428
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Konferensbidrag (refereegranskat)abstract
- This paper reports a self-propelled microfluidichematocrit (HCT) test that uses the correlation betweenblood hematocrit and wicking distance of blood in a specialpaper matrix. The enabling feature is a novel blood volumemetering method that allows sampling from the fingertipand reliably generates a highly precise blood volume of47.7 ± 1.9 μl (CV 4%) that is transferred into a porouspaper matrix. A dissolvable valve ensures a relaxed timewindow for blood sampling, making it highly user-friendlyand resilient to overfilling. The presented hematocrit teststrip poses a simple, cheap, equipment-free solution forpatient-centric hematocrit measurements.
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4. |
- Hauser, Janosch, et al.
(författare)
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A microfluidic device for TEM sample preparation
- 2020
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 20:22, s. 4186-4193
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Tidskriftsartikel (refereegranskat)abstract
- Transmission electron microscopy (TEM) allows for visualizing and analyzing viral particles and has become a vital tool for the development of vaccines and biopharmaceuticals. However, appropriate TEM sample preparation is typically done manually which introduces operator-based dependencies and can lead to unreliable results. Here, we present a capillary-driven microfluidic single-use device that prepares a TEM grid with minimal and non-critical user interaction. The user only initiates the sample preparation process, waits for about one minute and then collects the TEM grid, ready for imaging. Using Adeno-associated virus (AAV) particles as the sample and NanoVan (R) as the stain, we demonstrate microfluidic consistency and show that the sample preparation quality is sufficient for automated image analysis. We further demonstrate the versatility of the microfluidic device by preparing two protein complexes for TEM investigations using two different stain types. The presented TEM sample preparation concept could alleviate the problems associated with human inconsistency in manual preparation protocols and allow for non-specialists to prepare TEM samples.
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5. |
- Hauser, Janosch, et al.
(författare)
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An autonomous blood microsampling device enabling metered large-volume dried plasma spots (DPS)
- 2018
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Ingår i: 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018. - : Chemical and Biological Microsystems Society. - 9781510897571 ; , s. 1737-1739
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Konferensbidrag (refereegranskat)abstract
- This work introduces a novel principle for volume metering of passively separated blood plasma, empowered by an air pinch-off structure and the high capillary force of a paper matrix. The presented microfluidic device enables the autonomous generation of large-volume dried plasma spots (DPS) with 16 µl of plasma from 50-100 µl of human whole blood within less than 10 minutes. Providing large-volume DPS increases the confidence level of detecting low concentration analytes and constitutes a step towards using blood microsampling in the everyday blood analysis routine.
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6. |
- Hauser, Janosch, et al.
(författare)
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An Autonomous Microfluidic Device for Generating Volume-Defined Dried Plasma Spots
- 2019
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 91:11, s. 7125-7130
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Tidskriftsartikel (refereegranskat)abstract
- Obtaining plasma from a blood sample and preparing it for subsequent analysis is currently a laborious process involving experienced health-care professionals and centrifugation. We circumvent this by utilizing capillary forces and microfluidic engineering to develop an autonomous plasma sampling device that filters and stores an exact amount of plasma as a dried plasma spot (DPS) from a whole blood sample in less than 6 min. We tested 24 prototype devices with whole blood from 10 volunteers, various input volumes (40-80 mu L), and different hematocrit levels (39-45%). The resulting mean plasma volume, assessed gravimetrically, was 11.6 mu L with a relative standard deviation similar to manual pipetting (3.0% vs 1.4%). LC-MS/MS analysis of caffeine concentrations in the generated DPS (12 duplicates) showed a strong correlation (R-2 = 0.99) to, but no equivalence with, concentrations prepared from corresponding plasma obtained by centrifugation. The presented autonomous DPS device may enable patient-centric plasma sampling through minimally invasive finger-pricking and allow generatation of volume-defined DPS for quantitative blood analysis.
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8. |
- Hauser, Janosch D.
(författare)
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Capillary-Driven Microfluidic Devices for Sample Preparation of Bio-Medical Specimens
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sample preparation is an integral part of bio-medical analysis routines, as it makes specimens of interest compatible with downstream instrumentation. Correct and proper sample preparation is of critical importance for reliable analysis results. However, conventional preparation procedures often entail numerous manual user interactions, which cause variations in sample quality and can lead to biased results. Microfluidics is a promising technology to address these problems since on-chip integration of sample preparation steps, such as volume metering, liquid handling, and sample fixation, can minimize critical user interactions. This thesis explores capillary-driven microfluidic devices for sample preparation of bio-medical specimens in patient-centric blood analysis workflows and laboratory environments. Patient-centric blood analysis, where patients take and send samples to a central laboratory for quality-assured readout, is an emerging field where capillary-driven microfluidic solutions can enable consistent sample preparation in remote locations. Blood plasma, the gold standard in blood analysis routines, is typically extracted by centrifugation, which is not readily available in remote settings. To address this limitation, we realized a microfluidic device for capillary-driven blood plasma separation from undiluted human whole blood. Based on this approach, we developed a device that generates a volume-defined dried plasma spot ready to be shipped to a laboratory for mass spectrometry. Using the same plasma separation approach, we developed a device that performs the critical analyte binding step of a multiplexed immunoassay at the time of sample collection. Sample drying and shipment to a laboratory then allow to make use of the unparalleled performance of highly specialized laboratory equipment. Along the same line of patientcentric workflows, we showed that specially treated dry blood samples enablered and white blood cell quantification with good correlation to gold standard hematology analyzer data. In addition, this thesis describes microfluidic devices that prepare samples in laboratory environments. We present microfluidic alternatives to manual procedures for the preparation of virus particles and proteins for transmission electron microscopy, and for the preparation of liquid biopsy samples for cytology investigations.
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9. |
- Hauser, Janosch, et al.
(författare)
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High-Yield Passive Plasma Filtration from Human Finger Prick Blood
- 2018
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Ingår i: Analytical Chemistry. - : AMER CHEMICAL SOC. - 0003-2700 .- 1520-6882. ; 90:22, s. 13393-13399
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Tidskriftsartikel (refereegranskat)abstract
- Whole-blood microsampling provides many benefits such as remote, patient-centric, and minimally invasive sampling. However, blood plasma, and not whole blood, is the prevailing matrix in clinical laboratory investigations. The challenge with plasma microsampling is to extract plasma volumes large enough to reliably detect low-concentration analytes from a small finger prick sample. Here we introduce a passive plasma filtration device that provides a high extraction yield of 65%, filtering 18 mu L of plasma from 50 mu L of undiluted human whole blood (hematocrit 45%) within less than 10 min. The enabling design element is a wedge-shaped connection between the blood filter and the hydrophilic bottom surface of a capillary channel. Using finger prick and venous blood samples from more than 10 healthy volunteers, we examined the filtration kinetics of the device over a hematocrit range of 35-55% and showed that 73 +/- 8% of the total protein content was successfully recovered after filtration. The presented plasma filtration device tackles a major challenge toward patient-centric blood microsampling by providing high-yield plasma filtration, potentially allowing reliable detection of low-concentration analytes from a blood microsample.
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