A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) Detection
Blood testing is a clinical diagnostic tool to evaluate physiological conditions, the immune system response, or the presence of infection from whole blood samples. Although conventional blood testing can provide rich biological information, it usually requires complicated and tedious whole blood pr...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Biosensors |
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| Online Access: | https://www.mdpi.com/2079-6374/12/12/1163 |
| _version_ | 1797461137381392384 |
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| author | Zhi-Xuan Lai Chia-Chien Wu Nien-Tsu Huang |
| author_facet | Zhi-Xuan Lai Chia-Chien Wu Nien-Tsu Huang |
| author_sort | Zhi-Xuan Lai |
| collection | DOAJ |
| description | Blood testing is a clinical diagnostic tool to evaluate physiological conditions, the immune system response, or the presence of infection from whole blood samples. Although conventional blood testing can provide rich biological information, it usually requires complicated and tedious whole blood processing steps operated by benchtop instruments and well-experienced technicians, limiting its usage in point-of-care (POC) settings. To address the above problems, we propose a microfluidic platform for on-chip plasma extraction directly from whole blood and in situ biomarker detection. Herein, we chose C-reactive protein (CRP) as the target biomarker, which can be used to predict fatal cardiovascular disease (CVD) events such as heart attacks and strokes. To achieve a rapid, undiluted, and high-purity on-chip plasma extraction, we combined two whole blood processing methods: (1) anti-D immunoglobulin-assisted sedimentation, and (2) membrane filtration. To perform in situ CRP detection, we fabricated a three-dimensional (3D) microchannel with an embedded electrochemical (EC) sensor, which has a modular design to attach the blood collector and buffer reservoir with standard Luer connectors. As a proof of concept, we first confirmed that the dual plasma extraction design achieved the same purity level as the standard centrifugation method with smaller sample (100 µL of plasma extracted from 400 µL of whole blood) and time (7 min) requirements. Next, we validated the functionalization protocol of the EC sensor, followed by evaluating the detection of CRP spiked in plasma and whole blood. Our microfluidic platform performed on-chip plasma extraction directly from whole blood and in situ CRP detection at a 0.1–10 μg<i>/</i>mL concentration range, covering the CVD risk evaluation level of the high-sensitivity CRP (hs-CRP) test. Based on the above features, we believe that this platform constitutes a flexible way to integrate the processing of complex samples with accurate biomarker detection in a sample-to-answer POC platform, which can be applied in CVD risk monitoring under critical clinical situations. |
| first_indexed | 2024-03-09T17:16:06Z |
| format | Article |
| id | doaj.art-4c25b1dff1ec414786d35221c0a9ed5a |
| institution | Directory Open Access Journal |
| issn | 2079-6374 |
| language | English |
| last_indexed | 2024-03-09T17:16:06Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biosensors |
| spelling | doaj.art-4c25b1dff1ec414786d35221c0a9ed5a2023-11-24T13:37:40ZengMDPI AGBiosensors2079-63742022-12-011212116310.3390/bios12121163A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) DetectionZhi-Xuan Lai0Chia-Chien Wu1Nien-Tsu Huang2Graduation Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, TaiwanGraduation Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, TaiwanGraduation Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, TaiwanBlood testing is a clinical diagnostic tool to evaluate physiological conditions, the immune system response, or the presence of infection from whole blood samples. Although conventional blood testing can provide rich biological information, it usually requires complicated and tedious whole blood processing steps operated by benchtop instruments and well-experienced technicians, limiting its usage in point-of-care (POC) settings. To address the above problems, we propose a microfluidic platform for on-chip plasma extraction directly from whole blood and in situ biomarker detection. Herein, we chose C-reactive protein (CRP) as the target biomarker, which can be used to predict fatal cardiovascular disease (CVD) events such as heart attacks and strokes. To achieve a rapid, undiluted, and high-purity on-chip plasma extraction, we combined two whole blood processing methods: (1) anti-D immunoglobulin-assisted sedimentation, and (2) membrane filtration. To perform in situ CRP detection, we fabricated a three-dimensional (3D) microchannel with an embedded electrochemical (EC) sensor, which has a modular design to attach the blood collector and buffer reservoir with standard Luer connectors. As a proof of concept, we first confirmed that the dual plasma extraction design achieved the same purity level as the standard centrifugation method with smaller sample (100 µL of plasma extracted from 400 µL of whole blood) and time (7 min) requirements. Next, we validated the functionalization protocol of the EC sensor, followed by evaluating the detection of CRP spiked in plasma and whole blood. Our microfluidic platform performed on-chip plasma extraction directly from whole blood and in situ CRP detection at a 0.1–10 μg<i>/</i>mL concentration range, covering the CVD risk evaluation level of the high-sensitivity CRP (hs-CRP) test. Based on the above features, we believe that this platform constitutes a flexible way to integrate the processing of complex samples with accurate biomarker detection in a sample-to-answer POC platform, which can be applied in CVD risk monitoring under critical clinical situations.https://www.mdpi.com/2079-6374/12/12/1163microfluidicswhole blood processingelectrochemical (EC) detectionpoint-of-care (POC) settingscardiovascular disease (CVD) |
| spellingShingle | Zhi-Xuan Lai Chia-Chien Wu Nien-Tsu Huang A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) Detection Biosensors microfluidics whole blood processing electrochemical (EC) detection point-of-care (POC) settings cardiovascular disease (CVD) |
| title | A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) Detection |
| title_full | A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) Detection |
| title_fullStr | A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) Detection |
| title_full_unstemmed | A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) Detection |
| title_short | A Microfluidic Platform with an Embedded Miniaturized Electrochemical Sensor for On-Chip Plasma Extraction Followed by In Situ High-Sensitivity C-Reactive Protein (hs-CRP) Detection |
| title_sort | microfluidic platform with an embedded miniaturized electrochemical sensor for on chip plasma extraction followed by in situ high sensitivity c reactive protein hs crp detection |
| topic | microfluidics whole blood processing electrochemical (EC) detection point-of-care (POC) settings cardiovascular disease (CVD) |
| url | https://www.mdpi.com/2079-6374/12/12/1163 |
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