Designing Paper-Based Immunoassays for Biomedical Applications
Abstract
:1. Introduction
1.1. Paper-based Immunoassays
1.2. Commercial Applications
1.3. Disadvantages
2. Components of Paper-Based Assays
2.1. Paper-Based Assay Formats: Dipstick and Lateral Flow Configurations
2.2. Paper Assay Components
2.2.1. Paper Substrate
2.2.2. Reporters
- Surface bound antibodies are able to bind antigens, i.e., their epitope is still accessible and functional.
- Immunoprobes interact with the environment in a way which does not impede the antibody’s ability to bind the antigen, e.g., particles do not aggregate in relevant conditions.
- Immunoprobes interact with the paper medium weakly and without undesirable precipitation, and can diffuse through the paper strip while producing minimal background.
2.2.3. Antibodies that Bind to the Target
3. Metrics for Paper Assay Performance
3.1. Description of Target-Antibody Binding
3.2. Sensitivity and Specificity
4. Factors Impacting Paper Assay Performance
4.1. Fluidic Properties of The Paper Strip
4.2. Sample Preparation
5. Novel Modifications of Paper-Based Assays
5.1. Modifications and Improvements of Paper-Based Assays
5.1.1. Paper Enhancements
5.1.2. NP Enhancements
5.1.3. Application of External Readout or Quantification Devices
6. Challenges of Paper-Based Assays
6.1. Challenges Associated with the Biological Reagents
6.2. Substrate Related Challenges
6.3. Probe Related Challenges
6.4. Environment Related Challenges
6.5. Sample Related Challenges
7. Conclusions and Future Prospects
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Sensitivity [73] Probability of Detecting the Target Molecule when Present | Specificity [73] Probability of not Detecting the Target Molecule when Absent | ||
(4) | (5) | ||
: The number of times the test detected the target molecule in a sample when it was present. : The number of times the test failed to detect the target molecule when it was present. | : The number of times the test did not detect the target molecule in a sample when it was not present. : The number of times the test detected the target molecule when it was not present. |
Classification | LOD | Linear Range | Advantages | Limitations | References |
---|---|---|---|---|---|
Optical readout | ng/mL range | ng/mL to ug/mL | Quick Single step run Inexpensive Easy to operate anywhere | Low sensitivity for certain applications | [82] |
Optical enhancers | |||||
- Isotachophoresis | 60–400 fold improvement | 0.1–10 mg/L | Improved sensitivity Easy to operate | Signal depletion over time | [94] |
- NP aggregation | 1000 fold improvement | 0.5 pM–50 nM | Additional operation step, less robust to climate conditions | [44] | |
- secondary probe | 51 (96), 100 (95), 1000 (97) fold improvement | 0.01–30 ng/mL | Additional binding event | [95,96,97] | |
- probe growth | 100-fold (99,100) | 1010–1013 RNA copies | Less control in probe growth between samples | [98,99,100] | |
Fluorescence readout | ng-pg/mL range | ng/mL to 10 μg/mL | Up to 1000-fold improvement (94) | Special equipment required, access to electricity | [94,101,102] |
SERS | ng/mL (81,105) | 1–100 ng/mL, 102–106 cfu/mL | Up to 10000-fold improvement (105) | Expensive equipment and trained personnel | [82,103,104] |
Electrochemical | ng-μg/mL | 0.1–1.0 ng/mL | [105,106] | ||
Thermal contrast | nM range | 10−7 to 10−2 titer | [107,108] |
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Hristov, D.R.; Rodriguez-Quijada, C.; Gomez-Marquez, J.; Hamad-Schifferli, K. Designing Paper-Based Immunoassays for Biomedical Applications. Sensors 2019, 19, 554. https://doi.org/10.3390/s19030554
Hristov DR, Rodriguez-Quijada C, Gomez-Marquez J, Hamad-Schifferli K. Designing Paper-Based Immunoassays for Biomedical Applications. Sensors. 2019; 19(3):554. https://doi.org/10.3390/s19030554
Chicago/Turabian StyleHristov, Delyan R., Cristina Rodriguez-Quijada, Jose Gomez-Marquez, and Kimberly Hamad-Schifferli. 2019. "Designing Paper-Based Immunoassays for Biomedical Applications" Sensors 19, no. 3: 554. https://doi.org/10.3390/s19030554