A Protein Concentration Measurement System Using a Flexural Plate-Wave Frequency-Shift Readout Technique
Abstract
:1. Introduction
2. Design and Fabrication of the Proposed FPW Biosensor
2.1. Biosensor Microfabrication Technology
- Low energy loss of acoustic transmission in liquid medium
- Low design complexity of the oscillator
- Isolating the electrical circuit from the liquid medium
2.2. FPW Allergy Biosensor Structure and Characteristics
- Step 1: The chip is treated with a cystamine solution (0.02 M) for 1 h, washed with DI water three times and air-dried.
- Step 2: The chip is dipped into 2.5 wt% aqueous glutaraldehyde cross-linking reagent for 1 h and washed with DI water three times and air-dried.
- Step 3: After the highly purified, the IgE antibody layer is coated on the surface of the backside glutaraldehyde layer, and injecting Tween-20 wash buffer three times.
- Step 4: A diluted bovine serum albumin (BSA) layer is used for blocking and incubating the IgE antibody-coated surface to avoid nonspecific absorption and injecting diluted human IgE antigen.
2.3. FPW Allergy Biosensor with Frequency-Shift Readout IC Microsystem
3. Frequency-Shift Readout Circuit
Frequency Shift Readout Circuit Design
Linear Frequency Generator
Peak Detector
- Step 1: Initially, RESET1, RESET2, and RESET3 are biased at high to discharge C3, C4 and reset the D flip-flop.
- Step 2: The sine wave from FPW allergy biosensor's output is fed to VIN (vpeak_in1 or vpeak_in2 in Figure 8). When VIN is higher than VPEAK_new, OPA1 will turn on MN604. Then, C3 is charged until VPEAK_new = VIN.
- Step 3: MN603 is off to isolate VPEAK_new from VPEAK_max. If VPEAK_new is higher than VPEAK_max, OPA2 will trigger the D flip-flop. Then, EN (En1 or En2 in Figure 8) is pulled high to turn MN603 on. Hence, VPEAK_max is pulled close to VPEAK_new through MN603. If VPEAK_new is not higher than VPEAK_max, VPEAK_$max keeps the prior high voltage value.
- Step 4: When VPEAK_max is equal to VPEAK_new, RESET3 will be pulled up high to resetthe D flip-flop to set EN = 0. VPEAK_new and VPEAK_max are isolated again by MN603.
4. Implementation and Measurement
5. Conclusions
Acknowledgments
References
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ELSA | CLIA | Abbot AxSYM (FPIA) | FPW-based Microsystem | |
---|---|---|---|---|
Method | Enzyme Immunoassay Colorimetric | Enzyme Immunoassay, Chemiluminescence | Automated Latex Enhanced Immunoassay | Acoustic/piezoelectric Microsensor |
Principle | Streptavidin Biotin Based Sandwich Assay | Streptavidin Biotin Based Sandwich Assay | Polystyrene Latex Agglutination | Flexural Plate-wave Based Mass Sensing |
Calibrators (IU·mL−1) (in human serum) | 0, 5, 25, 50, 150 (IRP 75/502) | 0, 5, 25, 50, 150, 400 (IRP 75/502) | 0, 50, 100, 200, 500, 1,000 | 0, 73.6, 147.2, 294.4, 588.8, 1,177.6 |
Sample (μL/well) | 25 | 25 | 1,500 | <5 |
Total operation time (min) | 120–150 | 120–150 | 60–120 | <10 |
Sensitivity (IU·mL−1) | 1.0 | 1.0 | 1.0 | 1.0 |
Safety | No radioactive or toxic waste | No radioactive or toxic waste | No radioactive or toxic waste | No radioactive or toxic waste |
Equipment cost (USD) | ∼10,000 | ∼23,000 | ∼100,000 | ∼150 |
Dimension (cm3) | ∼40 × 30 × 11 | ∼40 × 30 × 33 | ∼160 × 85 × 152 | <25 × 10 × 5 |
Disposable | Yes | Yes | Yes | Yes |
Chip size | 9.6 mm × 6.8 mm |
---|---|
Wavelength (Periodicity) | Enzyme Immunoassay Colorimetric |
No. of finger pairs | 25 |
Finger width/finger spacing | 20 μm/20 μm |
Acoustic aperture | 3.2 mm |
Acoustic path length | 3.58 mm |
Center frequency | 9.1 MHz |
Proposed | [31] | |
---|---|---|
Implementation technique | system on chip | PCB discretes |
Measurement method | peak detection | phase detection |
Process (μm) | 0.18 | N/A |
Supply voltage (V) | 1.8 | +5, −5, and 3.3 |
Frequency (MHz) | 0.1 | 4.2 |
Power (mW) | 48 | N/A |
Year | 2012 | 2008 |
© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Wang, C.-C.; Sung, T.-C.; Hsu, C.-H.; Tsai, Y.-D.; Chen, Y.-C.; Lee, M.-C.; Huang, I.-Y. A Protein Concentration Measurement System Using a Flexural Plate-Wave Frequency-Shift Readout Technique. Sensors 2013, 13, 86-105. https://doi.org/10.3390/s130100086
Wang C-C, Sung T-C, Hsu C-H, Tsai Y-D, Chen Y-C, Lee M-C, Huang I-Y. A Protein Concentration Measurement System Using a Flexural Plate-Wave Frequency-Shift Readout Technique. Sensors. 2013; 13(1):86-105. https://doi.org/10.3390/s130100086
Chicago/Turabian StyleWang, Chua-Chin, Tzu-Chiao Sung, Chia-Hao Hsu, Yue-Da Tsai, Yun-Chi Chen, Ming-Chih Lee, and I-Yu Huang. 2013. "A Protein Concentration Measurement System Using a Flexural Plate-Wave Frequency-Shift Readout Technique" Sensors 13, no. 1: 86-105. https://doi.org/10.3390/s130100086
APA StyleWang, C.-C., Sung, T.-C., Hsu, C.-H., Tsai, Y.-D., Chen, Y.-C., Lee, M.-C., & Huang, I.-Y. (2013). A Protein Concentration Measurement System Using a Flexural Plate-Wave Frequency-Shift Readout Technique. Sensors, 13(1), 86-105. https://doi.org/10.3390/s130100086