Microfluidic Blood Separation: Key Technologies and Critical Figures of Merit
Abstract
:1. Introduction
2. Key Device Performance Figures of Merit: Definitions
2.1. Input and Output Concentrations
2.2. Efficiency
2.3. Purity
2.4. Flow Rate and Throughput
3. Passive Techniques
4. Passive Blood Separations
4.1. Passive Separation of Blood Cells
4.2. Passive Separation of Blood Pathogens
5. General Considerations and Parameters for Active Separations
Contrast Factor
6. Active Techniques
6.1. Electric Forces: Dielectrophoresis (DEP)
6.2. Magnetic Forces: Magnetophoresis
6.3. Acoustic Forces: Acoustophoresis
6.4. Thermal Forces: Thermophoresis
6.5. Optoelectronic Forces: Optoelectronic Tweezers (OETs)
7. Measurement and Quantification Techniques for Microfluidic Separated Blood Fractions
8. Active Blood Separation Applications
8.1. Active Separation of Blood Cells
8.2. Active Separation of Blood Pathogens
9. Discussion
10. Conclusions and Outlook
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Blood Contents to Separate | Sample Initial Concentration Volume (Cells/mL) | Separation Method | Target Sample | Separation Efficiency (%) | Purity (%) | Flow Rate (mL/min) | Cell Throughput (Cells/min) | Final Conc. (Cells/mL) | Label-Free (Y/N) | Ref. |
---|---|---|---|---|---|---|---|---|---|---|
Plasma and NCI-H1299 from RBCs | Inertial: contraction expansions | Plasma and NCI-H1299 lung cancer cells | 96 and 95 | 70–80 | - | - | Yes | [179] | ||
WBCs from RBCs | 500× dilution | Multidimensional double spiral | WBC (polymorphonuclear leucocytes) | >80 | >85 | 9.2 | − | 12× compared with input | Yes | [72] |
RBCs, WBCs, and dendritic cells | Whole blood | Inertial: spiral | Dendritic cells | 77 | − | − | − | − | Yes | [60] |
MCF-7,Hela, and PC-3 from diluted blood | Inertial: spiral with sheath flow | MFC-7 Hela PC-3 | >90 | - | 1.4 total flowrate for separation mode | >80 | - | Yes | [44] | |
Breast cancer cells (T47D) from blood | Diluted blood (1:50) | Inertial: cascaded sinusoidal | T47D | ∼56 | 1 | − | Yes | [76] | ||
Plasma from blood | Whole blood | Passive: microfiltration, sedimentation, and wetting contrast | Plasma | ∼100 | ∼15 μL | - | - | - | Yes | [180] |
RBCs from whole blood | Diluted whole blood () | Dielectrophoresis | RBC | - | - | − | Yes | [106] | ||
Plasma from blood | Whole blood | Dielectrophoresis | Plasma | ∼98 | ∼100 | − | − | Yes | [153] | |
RBCs from fixed RBCs | Diluted whole blood | Dielectrophoresis | RBCs and fixed RBCs | − | − | − | Yes | [107] | ||
Live from dead monocytes | Dielectrophoresis | Live monocytes | 90 | − | − | − | − | Yes | [150] | |
WBCs, RBCs, and CTCs | Diluted blood | Hybrid: inertial and magnetophoresis | CTCs | ∼95 | 93 | 1 | - | - | No | [156] |
WBCs from RBCs | Whole blood | Whole blood magnetophoresis | WBCs and RBCs | 89.5 | − | − | − | Yes | [157] | |
Malaria-infected RBCs from magnetic beads | 80% parasitemia | Magnetophoresis | − | 25 | − | 0.4 | − | − | Yes | [155] |
CTC (MCF-7) from whole blood | − | Hybrid: inertial spiral, DLD, and fluourescence flow cytometry | CTCs | − | 92 | − | − | − | Separation yes, cytometry no | [82] |
Tumor cells, RBCs, and WBCs | Diluted blood () and spiked tumor cells () | Hybrid: inertial spiral and DLD | CTCs | 99.9 | 93.59 | − | − | Yes | [81] | |
WBCs, RBCs, and trypanosomes (T. cyclops) | Diluted blood sample (10x) with spiked parasite | Inertial: DLD | WBCs, RBCs, and trypanosomes | >94 (WBCs) >90 (RBCs) >80 (trypanosomes) | − | − | − | Yes | [73] | |
RBCs from whole blood | Diluted whole blood | DEP | RBCs | − | − | − | Yes | [106] | ||
Plasma from blood | Whole blood | DEP | Plasma | ∼98 | ∼100 | − | − | Yes | [153] | |
RBCs from fixed RBCs | Diluted whole blood | DEP | RBCs and fixed RBCs | − | − | − | Yes | [107] | ||
Monocytes (U937) and macrophages (U937) | DEP | Monocytes | 69.43 | − | to | − | Yes | [149] | ||
WBCs from RBCs | Diluted blood | Magnetophoresis | WBCs | − | 93 | − | No | [181] | ||
Mononuclear cells (MNCs) | Diluted blood (20x) | Acoustophoresis | WBCs | >43 (WBCs) and >87 (MNCs) | 54 (WBCs) 55 (MNCs) | − | Yes | [182] | ||
WBCs, lymphocytes, monocytes, and granulocytes | − | Acoustophoresis | − | 96.8 (WBCs) 66.7 (lynphocytes) 99 (monocytes and granulocytes) | 96.5 (WBCs) 71.8 (lynphocytes) 10.1 (monocytes) 98.8 (granulocytes) | 0.1 | − | Yes | [183] | |
Tumor cells (U87 glioma cells) from RBCs | Diluted blood spiked with tumor cells/mL | Acoustophoresis | Glioma tumor cells | 90 | − | − | − | − | [161] | |
CTCs, WBCs from lysed blood | Lysed RBCs from whole blood with WBCs spiked with CTCs | Acoustophoresis | DU145 (prostate cancer cells) and MCF7 (breast cancer cells) | 42 (CTCs) | 99.75 (WBC depletion efficiency) | − | − | − | No | [184] |
RBCs from bacteria | Diluted blood (20%) | Acoustophoresis | Bacteria | >40 (E. coli) >60 (S. aureus) >50 (P. aeruginosa) | − | 0.01 | − | – CFU/mL | No | [176] |
T cells from RBCs | Diluted blood | Acoustophoresis | T cells | 90.5 | 99 | 0.4 | − | − | No for T cells and yes for RBCs | [185] |
Microorganism Separated from Blood | Sample Initial Concentration Volume (CFU/mL) | Separation Method | Separation Efficiency (%) | Purity (%) | Flow Rate (μL/min) | Cell Throughput (Cells/mL) | Label-Free (Y/N) | Ref. |
---|---|---|---|---|---|---|---|---|
Malaria | − | Passive: detecting by light | − | − | − | − | No | [83] |
Listeria monocytogenes Staphylococcus aureus (Quickly sepsis clinical diagnostics) | from to | Active: Magnetic separation | 93.14 | 90 | − | − | Yes | [186] |
Sepsis S. aureus, E. coli, P. aeruginosa, and Methicillin-resistant S. aureus | Electrostatic and hydrophobic interactions | from to | − | − | − | Yes | [162] | |
Sepsis S. aureus, P. aeruginosa, and E. coli | 1.42 | Active: Magnetic separation and micro-Raman spectroscopy | 60–70 | − | − | Yes | [187] | |
E. coli | Active: dielectrophoresis | 97 | − | from to | No | [169] | ||
S. enteritidis and E. coli | and | Electrophoresis | Reduce time and equipment | − | − | − | Yes | [188] |
HIV RNA | Whole blood | Passive: filtration and flourescent | Depends on particle size, from 47.6% to 81.9% | virus copies per mL | − | No | [87] | |
E. coli | – | Electrophoresis by gel | 0.3–0.6 | − | − | − | Yes | [88] |
RBC | − | Magnetophoresis | 100 | − | − | − | No | [164] |
E. coli | – | Magnetophoresis | − | − | from to | − | Yes | [163] |
Sepsis | Fluorescence | 100 | − | − | Yes | [85] | ||
E. coli and RBCs | and | Flourescence | 54 and 97 | − | Yes | [86] | ||
P. aeruginosa, S. aureus, and E. coli | DEP | 94.8 | − | 1 | − | Yes | [166] | |
E. coli and RBCs | and | Acousto-phoresis | − | 96.0 and 95.85 | 9 and 7 | − | Yes | [177] |
Salmonella and RBCs | Acoustophoresis | 60 and 90 | − | 10–30 and 10–70 | − | Yes | [178] | |
E. coli | DEP | milk: 90 buffer: 70.7 human blood: 80.2 | − | 5 | − | Yes | [171] | |
E. coli | DEP | 87.2 | − | 1.8 | − | Yes | [167] | |
E. coli and C. albicans | DEP (+/−) | 97 (DEP+), 94 (DEP−) and 92 (DEP+), 56 (DEP−) | − | − | − | Yes | [168] |
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Torres-Castro, K.; Acuña-Umaña, K.; Lesser-Rojas, L.; Reyes, D.R. Microfluidic Blood Separation: Key Technologies and Critical Figures of Merit. Micromachines 2023, 14, 2117. https://doi.org/10.3390/mi14112117
Torres-Castro K, Acuña-Umaña K, Lesser-Rojas L, Reyes DR. Microfluidic Blood Separation: Key Technologies and Critical Figures of Merit. Micromachines. 2023; 14(11):2117. https://doi.org/10.3390/mi14112117
Chicago/Turabian StyleTorres-Castro, Karina, Katherine Acuña-Umaña, Leonardo Lesser-Rojas, and Darwin R. Reyes. 2023. "Microfluidic Blood Separation: Key Technologies and Critical Figures of Merit" Micromachines 14, no. 11: 2117. https://doi.org/10.3390/mi14112117
APA StyleTorres-Castro, K., Acuña-Umaña, K., Lesser-Rojas, L., & Reyes, D. R. (2023). Microfluidic Blood Separation: Key Technologies and Critical Figures of Merit. Micromachines, 14(11), 2117. https://doi.org/10.3390/mi14112117