A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording
Abstract
:1. Introduction
- A microfluidic device allowing stable, reliable and automatic BLM formation.
- A fast low-noise electronic interface ables to acquire pA currents.
- A compact, robust and scalable system containing an array of microfluidic devices and electronic interface.
2. Proposed Transimpedance Amplifier
2.1. Ion Channel Recording Platform
- Three disposable microfluidic devices manufactured on a glass substrate holding 4 BLMs each [12].
- A small PCB hosting two CMOS 2-channel low-noise current-to-digital amplifiers that can measure pA currents.
- A motherboard with a digital control unit implemented in a Field Programmable Gate Array (FPGA) [11].
- Read the front-end output voltage VOUT;
- Compare VOUT with the reference voltage VCM;
- Change DC voltage VOFF so that it becomes equal to VCM + Voff,ele. (Note reference electrode is tight to VCM).
2.2. Microfluidic Device
2.3. Sensing Frontend Rationale
- Active phase. During this phase where Req is the equivalent trans-resistance of the amplifier, which is given by:
- Reset phase. During this phase the output voltage is kept constant while the rest of the circuit reset.
2.4. ADC
2.5. Stimulus Generation and Offset Compensation
2.6. Subtractor
2.7. Noise Analysis
- all the stages prior to the sampling are treated as linear time-invariant systems;
- node x takes into account low-pass filtering done by the Sallen-Key but not the sampling; there is not a direct correspondence of node x in the schematic diagram (Figure 5b).
- node OUT is renamed into y to get more compact equations.
- -
- The most direct method of reducing folding noise is lowering the USR, which defines how many times the noise folds back into the baseband. This can be easily done by lowering fp, but this directly affects the bandwidth of the system and the sampling error [14]. Moreover, if 1/fp becomes greater than the reset pulse duration τR then Equations (18) and (19) are no longer valid, since cross-correlation power computed from Equation (17) must be taken into consideration.
- -
- Another important parameter is the period TR, which appears in both USR and pre-factor. It should be small to lower USR while it should be big to lower the pre-factor (τR/TR)2. Since TR is squared in the pre-factor term then it is better to make it as high as possible. This relation between noise and parameter TR is confirmed by periodic-steady-state noise (pss-noise) analysis and it is predicted by our mathematical model, see Figure 10.
- -
- Another way of reducing the folding noise is to keep Gx(f) as low as possible. This directly translates into using a low-noise OTA and lowering the input capacitance CIN as well as the feedback capacitance C1, creating a noise-bandwidth trade-off.
3. Experimental Results
3.1. Implementation
3.2. Noise Measurements
3.3. Offset Compensation Loop and Subtractor
3.4. Ion Channel Recording
3.4.1. Gramicidin-A
3.4.2. α-Haemolysin
3.4.3. KcsA Potassium Channel
3.5. State-of-the-Art Comparison
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Component | C1 | C2 | C3 | C4 | R4 | R3 | TR | τR |
---|---|---|---|---|---|---|---|---|
Value | 1 pF | 22 pF | 1 pF | 102.4 pF | 1 MΩ | 2.2 kΩ | 102.4 μs | 4.8 μs |
Theory (18) | Simulation | Measure | |
---|---|---|---|
RMS NOISE at 10 kHz | 380 fA | 400 fA | 420 fA |
Conditions | CIN = CP = 3 pF | CIN = CP = 3 pF | Open-input |
Paper | Noise floor @ Room Temperature | Embedded ADC | Analog Power Consumption | Digital Power Consumption | Input Capacitance for Characterization of Noise Floor | Operating Bandwidth [kHz] | Gain [GΩ] | Technology Node |
---|---|---|---|---|---|---|---|---|
[21] | 12 fA/√Hz | NO | - | - | - | 10.000 | <1 | CMOS 0.13 μm |
[20] | 2 fA/√Hz | NO | 3 μW | - | - | 6 | >1 | CMOS 0.13 μm |
[37] | 0.5 fA/√Hz | NO | - | - | 1 pF | 1000 | *1 | - |
[39] | 6 fA/√Hz | NO | 1.5 mW | - | 7 pF | 50 | - | CMOS 0.5 μm |
[38] | 4 fA/√Hz | NO | 45 mW | - | 800 fF | 10,000 | 0.06 | CMOS 0.35 μm |
[40] | 11.6 fA/√Hz | NO | 5.22 mW | - | - | 1400 | 0.01 | CMOS 0.18 μm |
[13] | 3 fA/√Hz@B = 625 Hz 12 fA/√Hz @B = 10 kHz | YES | 20 mW | 20 mW | 3 pF | 10 | 2.25 | CMOS 0.35 μm |
This work | 4 fA/√Hz*2 @B = 7.5 kHz 6 fA/√Hz *2 @B = 175 kHz | YES | 21 mW | 20 mW | 3 pF | 100 | 2.25 | CMOS 0.35 μm |
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Crescentini, M.; Bennati, M.; Saha, S.C.; Ivica, J.; De Planque, M.; Morgan, H.; Tartagni, M. A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording. Sensors 2016, 16, 709. https://doi.org/10.3390/s16050709
Crescentini M, Bennati M, Saha SC, Ivica J, De Planque M, Morgan H, Tartagni M. A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording. Sensors. 2016; 16(5):709. https://doi.org/10.3390/s16050709
Chicago/Turabian StyleCrescentini, Marco, Marco Bennati, Shimul Chandra Saha, Josip Ivica, Maurits De Planque, Hywel Morgan, and Marco Tartagni. 2016. "A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording" Sensors 16, no. 5: 709. https://doi.org/10.3390/s16050709
APA StyleCrescentini, M., Bennati, M., Saha, S. C., Ivica, J., De Planque, M., Morgan, H., & Tartagni, M. (2016). A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording. Sensors, 16(5), 709. https://doi.org/10.3390/s16050709