Nanoparticle-Based Biosensing Assay for Universally Accessible Low-Cost TB Detection with Comparable Sensitivity as Culture
Abstract
:1. Introduction
1.1. Constraints of Current Methods
1.2. Novelty of the Paper
1.3. Novelty of the MACE Technique
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Instrumentation
2.3. Clinical Samples
2.4. Sputum Smear Microscopy (SSM) by Ziehl–Neelsen Staining
2.5. Standard Culture by the Lowenstein-Jensen Method
2.6. Nanoparticle-Based Colorimetric Biosensing Assay (NCBA)
2.7. Mathematical Modeling of the Mtb Population
2.8. GMNP-Cell Interaction for Transmission Electron Microscope (TEM) Imaging
2.9. Ethics
3. Results
3.1. GMNP
3.2. GMNP-Cells
3.3. Clinical Samples
3.4. NCBA vs. SSM vs. Culture
4. Discussion
4.1. Mechanism of GMNP-Cell Interaction
4.2. NCBA v.s SSM vs. Culture
4.3. NCBA for TB Incidence
4.4. NCBA for Detection of Early Onset of Disease
4.5. NCBA to Profile TB Population
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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City # | No. Samples | SSM | NCBA | Culture | ||||
---|---|---|---|---|---|---|---|---|
No. | Fraction | Positive | Negative | Positive | Negative | Positive | Negative | |
1 | 98 | 9% | 15 | 83 | 18 | 80 | 17 | 81 |
2 | 119 | 11% | 9 | 110 | 13 | 106 | 13 | 106 |
3 | 213 | 19% | 36 | 177 | 50 | 163 | 50 | 163 |
4 | 72 | 6% | 6 | 66 | 11 | 61 | 11 | 61 |
5 | 58 | 5% | 11 | 47 | 21 | 37 | 21 | 37 |
6 | 123 | 11% | 22 | 101 | 36 | 87 | 36 | 87 |
7 | 82 | 7% | 5 | 77 | 10 | 72 | 9 | 73 |
8 | 153 | 14% | 13 | 140 | 25 | 128 | 25 | 128 |
9 | 190 | 17% | 5 | 185 | 10 | 180 | 9 | 181 |
Total | 1108 | 100% | 122 | 986 | 194 | 914 | 191 | 917 |
Sensitivity | Specificity | PPV | NPV | Accuracy | |
---|---|---|---|---|---|
SSM | 63.9% (56.6–70.7) | 100.0% (99.6–100.0) | 100.0% | 93.0% (91.7–94.1) | 93.8% (92.2–95.1) |
NCBA | 100.0% (98.1–100.0) | 99.7% (99.1–99.9) | 98.5% (95.4–99.5) | 100.0% | 99.7% (99.2–99.9) |
End of Month | Symptoms | Est. Mtb Load in Patient, CFU/mL | Detectable by SSM and Est. Grade? | Detectable by NCBA? | Detectable by Culture? |
---|---|---|---|---|---|
1st | Not feeling well | 6.3 x100 | |||
2nd | Cough at night | 4.0 × 101 | No | Yes | Yes, result in 4th month |
3rd | Intense coughing | 2.5 × 102 | No | Yes | Yes, result in 5th month |
4th | Onset of hemoptoic cough or hemoptysis | 1.6 × 103 | No | Yes | Yes, result in 6th month |
5th | Onset of dyspnea | 9.1 × 103 | Yes, 1+ and 2+ | Yes | Yes, result in 7th month |
6th | Dyspnea | 3.9 × 104 | Yes, 3+ | Yes | Yes, result in 8th month |
7th | Dyspnea | 8.0 × 104 | Yes, 4+ | Yes | Yes, result in 9th month |
City | No. Samples | SSM+ | NCBA+ | Culture+ | ||
---|---|---|---|---|---|---|
>104 (High) | 101–103 (Low) | >104 (High) | 101–103 (Low) | >104 (High) | ||
1 | 98 | 15% | 3% | 15% | 2% | 15% |
2 | 119 | 8% | 3% | 8% | 3% | 8% |
3 | 213 | 17% | 7% | 17% | 7% | 17% |
4 | 72 | 8% | 7% | 8% | 7% | 8% |
5 | 58 | 19% | 17% | 19% | 17% | 19% |
6 | 123 | 18% | 11% | 18% | 11% | 18% |
7 | 82 | 6% | 6% | 6% | 5% | 6% |
8 | 153 | 8% | 8% | 8% | 8% | 8% |
9 | 190 | 3% | 3% | 2% | 2% | 3% |
Total | 1108 | 11% | 6% | 11% | 6% | 11% |
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Briceno, R.K.; Sergent, S.R.; Benites, S.M.; Alocilja, E.C. Nanoparticle-Based Biosensing Assay for Universally Accessible Low-Cost TB Detection with Comparable Sensitivity as Culture. Diagnostics 2019, 9, 222. https://doi.org/10.3390/diagnostics9040222
Briceno RK, Sergent SR, Benites SM, Alocilja EC. Nanoparticle-Based Biosensing Assay for Universally Accessible Low-Cost TB Detection with Comparable Sensitivity as Culture. Diagnostics. 2019; 9(4):222. https://doi.org/10.3390/diagnostics9040222
Chicago/Turabian StyleBriceno, Ruben Kenny, Shane Ryan Sergent, Santiago Moises Benites, and Evangelyn C. Alocilja. 2019. "Nanoparticle-Based Biosensing Assay for Universally Accessible Low-Cost TB Detection with Comparable Sensitivity as Culture" Diagnostics 9, no. 4: 222. https://doi.org/10.3390/diagnostics9040222