Application of automatic range control in DNA electrochemical signal acquisition instrument

DNA electrochemical signal acquisition instrument is a diagnostic instrument designed based on electrochemical analysis technology. Electrochemical analysis technology is currently a hot topic in determining DNA sequences. It has great advantages over surface analysis technology, gel electrophoresis technology, microcalorimetry, capillary electrophoresis, electrochemical analysis technology and chemiluminescence analysis technology. This design uses cyclic voltammetry to detect the current generated by DNA biochemical reactions, thereby making early diagnosis of acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML). The acquisition instrument has the characteristics of miniaturization, integration, in-situ, in-vivo, real-time and online detection.

The detection system of the electrochemical method is generally a three-electrode system: the working electrode is a gold electrode, on which DNA fragments and electroactive hybridization indicators used for detection are fixed; the reference electrode is a silver/silver chloride electrode; and the auxiliary electrode is a platinum electrode.

Generally, when using CHI660C and selecting cyclic voltammetry for electrochemical experiments, you need to set its sensitivity. Once the sensitivity is set inappropriately, it will affect the detection effect. Therefore, in order to improve the detection accuracy of the current signal, the DNA electrochemical signal acquisition instrument needs to have the function of automatically controlling the sensitivity.

This paper first briefly introduces the overall framework, functions and performance of the homemade DNA electrochemical signal acquisition instrument, then elaborates on the application of the automatic range control system in the signal acquisition module, and gives the corresponding hardware and software design solutions.

1 System Design

The entire DNA electrochemical signal acquisition instrument is mainly composed of four modules, as shown in Figure 1.

The processor module adopts TI's DSP processor TMS320F2806, which is mainly responsible for controlling the signal generation module and the signal acquisition module. At the same time, it processes the collected signals and sends them to the host computer.

The signal generation module includes 16-bit D/A, low-pass filter and constant potential instrument. Under the control of DSP, this module generates corresponding waveform signal according to the selected electrochemical detection method.

The signal acquisition module includes I/V conversion circuit, automatic range control circuit, voltage adjustment circuit, low-pass filter circuit and 16-bit A/D. Its function is to collect the current signal in the electrochemical reaction cell.

The electrochemical reaction cell module provides a place for the electrochemical reaction of the three-electrode system and transmits the current signal generated in the reaction to the signal acquisition module.

2 Design of automatic range control system

2.1 Design requirements for automatic range control systems

Considering that the current signal generated by general electrochemical reactions ranges from 1.0×10-7 to 1.0×10-3A, the circuit of the signal acquisition part in the DNA electrochemical signal acquisition instrument is required to be able to detect current signals in this range, and have strong anti-interference ability, low noise and signal distortion. In addition, the signal acquisition circuit also needs to have the function of digital control fast and accurate gear adjustment, and can automatically adjust the sensitivity according to certain conditions, that is, automatically upshift or downshift.

In general, the converted quantity should be within the A/D conversion linear region, and the analog quantity should be converted as much as possible in the area from 1/2 full scale to close to full scale, that is, the appropriate sensitivity is automatically selected according to the range of the unknown parameter value.

2.2 Design of automatic range control system

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The intelligent DNA electrochemical signal acquisition instrument realizes I/V conversion by automatically switching the range. Its principle is as follows:

Where: Imeasurement represents the current signal to be measured; K represents the sampling sensitivity; Vbias represents a constant bias voltage; VREF represents the reference voltage of A/D; S represents the digital signal value sampled by A/D; and n represents the number of conversion bits of the A/D converter.

Before designing the circuit, you can determine the range and conditions for switching the range based on actual needs, and then check whether the current range and accuracy meet the requirements under this condition.

2.2.1 Determination of measuring range

According to the design requirements of the automatic range control system, it is decided to set the instrument's range to 4 levels, and the sensitivity K between adjacent levels differs by 10 times. The I/V conversion resistors corresponding to the 4 levels are 1 MΩ, 100 kΩ, 10 kΩ and 1 kΩ respectively. The specific design is shown in Table 1.

2.2.2 Determination of switching range conditions

Since the current to be measured has positive and negative, that is, different directions, the voltage after I/V conversion also has positive and negative differences. In this design, the acquisition voltage range of the 16-bit A/D is 0~4.096 V, so a 2.5 V bias voltage is added to change the voltage range of the A/D acquisition to -2.5~+1.596 V. The conditions for the upper and lower limit shifts are determined below.

When the voltage signal is close to the full scale of A/D, or the signal is small, the A/D sampling will be distorted. Therefore, this design uses (2.5±1.5)V as the upper limit of A/D input, that is, 1.0 V and 4.0 V, which are the upper limits of negative and positive measurable voltages respectively. If the A/D sampling voltage value is less than 1.0 V or greater than 4.0 V, it exceeds the range of this gear and needs to be raised to a higher gear.

The ratio of the sensitivity between the lower limit shift gears is 10, so theoretically, the lower limit of the shift should be (2.5±1.5／10)V, but in order to prevent the measurement system from frequently switching the range, this design adds a 0.1 V wide shift connection area, so its lower limit is (2.5±(1.5-0.1)／10)V, that is, 2.36 V and 2.64 V, which are the negative and positive lower limits of the measurable voltage respectively. If the voltage value is between 2.36 and 2.64 V, it exceeds the range of this gear and needs to be downgraded.

From the perspective of the A/D sampling value S, its shifting conditions can be summarized as shown in Table 2.

2.2.3 Calculation of measurement current range and accuracy

In this design, a 16-bit A/D chip is used, so n=16, VREF=4.096 V, and Vbias=2.5 V. Therefore, from equation (1), it can be seen that there must be a corresponding relationship between I measurement and S:

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From Table 2, we know that the range of S is 0x3E80～0x9380 and 0xA500～0xFA00. Then, the range of I measurement in each level and its corresponding current accuracy can be obtained by formula (2), as shown in Table 3. From this table, we can see that the range and accuracy of the measured current basically meet the requirements of the instrument.

2.3 Hardware Circuit Design

This design uses a processor to control two digital potentiometers to adjust the sensitivity of I/V conversion, thereby realizing automatic range control of signal acquisition. Digital potentiometers are also called digitally controlled resistors. In any occasion where resistors are needed for parameter adjustment, calibration or control, digital potentiometers can be used to form programmable analog circuits. This design uses AD5242 as a coarse adjustment potentiometer, with a maximum resistance of 1 MΩ and a total of 256 taps. At the same time, AD5254 is used as a fine adjustment potentiometer, with a maximum resistance of 10 kΩ and a total of 256 taps. The circuit design block diagram of AD5242 and AD5254 is shown in Figure 2.

For these two types of digital potentiometers, the resistance between W and B is: RWB(D)=(D/256)RAB+RW, where D represents the input 8-bit binary code, ranging from 0 to 255; RAB refers to the resistance between A and B; and RW is the resistance of the sliding end caused by the internal switch.

As shown in Figure 2, for AD5242, RW1B1=(D/256)×1+60; for AD5254, RW2B2=(D/256)×10+75; the resistance between W1 and W2, RW1W2=RW1B1+RW2B2. The specific design of each range is shown in Table 4.

2.4 Software Design

The software design of the automatic range control system is shown in Figure 3. The specific working process is as follows:

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When the A/D sampling value S exceeds the upper or lower limit of the range, first determine whether the current range has reached the highest or lowest range. If not, shift up or down and then resample; otherwise, it means that the signal exceeds the detection range.

If S is within the current range, the processor will save the sampled value and send it to the host computer, ending a sampling.

3 Experimental results and analysis

For the small current of microampere level, the test results of each range are shown in Figure 4. When K=1e-006 A/V (1st range), the linearity of the data is the best and most accurate; and as the range gradually increases, the linearity of the data becomes worse and worse. Therefore, this instrument automatically sets the sensitivity K to 1st range, and the test results are consistent with 1 in Figure 4, thus achieving the effect of automatic range control without manual sensitivity setting. In the figure, I is the current; U is the scanning voltage.

For milliampere current, the detection results at each range are shown in Figure 5. When K=1e-003 A/V (4th range), all current signals can be collected, and the data is relatively accurate; as the range decreases, the current signal gradually exceeds the detection range, but the linearity is good within the detectable range. For this signal, as the current signal approaches zero, the sensitivity K of this instrument will gradually change from 4th range to 1st range, and then gradually change to 1st range as the current increases, thereby realizing automatic range control, and the effect is shown in 4 in Figure 5.

It can be seen from the experiment that the automatic range control system avoids manual setting of sensitivity, realizes automatic adjustment of the range, and achieves accurate detection of current signals in a wide range.

4 Conclusion

This paper introduces the DNA electrochemical signal acquisition instrument with DSP as the core, focusing on the design of the automatic range control system. The automatic range control method expands the detection range of the current signal caused by the DNA biochemical reaction and improves the accuracy of sampling, meeting the performance requirements of the instrument such as wide detection range and high precision.