Auto gain Ultra low signal transimpedance amplifier for Blood Diagnostic machine.

The front-end circuit of blood diagnostic machine consists of a light source, photodiode and transimpedance amplifier (TIA). Various researchers have used separate photodiode and the TIA circuit to measure absorbance for different wavelengths that made the circuit bulky and limited its application for measurement of specific parameters. At high gain of around 4000 plus normally any amplifier, including TIA becomes unstable. We are presenting here auto gain TIA that is stable and precise even at the gain of 4000. MSP432 32 BIT Arm Cortex 4 microcontroller with inbuilt precision analog to digital convertor is used for sensing, implementing auto gain selection logic and calculating the absorbance. With this circuit, we measured the absorbance up to 4.2 and satisfactory results with maximum error of 0.04 were achieved up to the range of 3.5 on the absorbance scale. Further, the performance of TIA is tested and found satisfactory for 300nm to 800nm wavelength range.


Introduction
Blood Diagnostic Machine performs tests for determination of physiological and biochemical conditions.The blood sample is collected in vacutainer blood collecting tubes and some additives are added to settle it and then test can be performed. The blood diagnostic machine uses the principle of spectrophotometry which is based on either fluorescence principle or absorbance principle [1][2]. It uses Beer-Lambert's law, which states the relation between the absorption of light and the material property through which light is transmitted as given by eq (1) and (2) T= ூ ூ బ = 10 ି∈ * * (1) A=є*C*l= log (T) (2) Where, T is transmittance, A is Absorbance, I is the intensity of light transmitted through the sample, ‫ܫ‬ is the intensity of light incident on the sample.
Block diagram of blood diagnostic machine is given in figure 1. Here, Optical source is used to generate signals, which is detected by the photodiode. This signal is amplified using TIA and given to a data  TIA is used to convert optical signal into an appropriate voltage which is then processed by the next stage of processing circuit. TIA with high gain is required to amplify low strength optical signal, But TIA becomes unstable at high gain. Many researchers have designed TIA for different applications like measurement of glucose, hemoglobin, blood group analysis. It is observed in the literature that the proper combination of photodiode and selecting corresponding design of TIA generates accurate results of blood parameters to measure different optical strength. But it makes a circuit bulky and limits its application to measure specific parameters [3][4][5]. The Designing of TIA plays an important role, such as precision in measurement, low noise and gain stability [6][7][8][9][10]. TIA with variable gain is the best solution to measure different strength of optical signal. To amplify different optical signal different gains can be used [11][12][13][14][15]. But it is always a difficult task to match the combination of resistor and capacitor to achieve proper bandwidth as per signal. Auto gain selection is required to avoid TIA to go into saturation for high strength of optical signal. So there is a need to design stable TIA, which amplifies low optical signals in the range of a precisely.
Here, the aim is to redesign the semiautomatic blood diagnostic machine in such a way that the internal signal conditioning circuit will be capable of detecting very low optical signal in order of pA and will be able to measure absorbance up to level 3.

Proposed System
The block diagram of the proposed system is as given below in figure 2 which is divided into two parts: i) The front-end circuit consists of a photodiode and TIA with auto gain facility ii) Microcontroller, recording and display unit.
The blood sample is placed between the light source-filter assembly and photodiode.Mechanical assembly with the stepper motors with efficient design of optical filter wheel is used to automate for precise measurement which supports inhale and exhale procedure of blood samples. Light is allowed to pass through the 10 mm passage of the blood sample using the software selected optical filter. Absorbance of light at a particular wavelength is measured. A precise auto gain-controlled TIA is used to amplify the signal. Auto gain is selected by the 32-bit microcontroller. All the gain resistances used to calculate gains are connected to analog multiplexer. Then the output is displayed on the LCD screen.  This work is focused on the design of TIA with auto-gain facility as highlighted in figure 2 for the above mentioned specifications for a blood diagnostic machine.

Methodology
Light source used for this experiment is the luminance film viewer.

Selection of Sensor
Si photodiode is selected because it offers very low dark current and allows reliable measurements in visible to near infrared range from low light to high light intensities.

Design of Transimpedance amplifier
TIA is used for amplifying the light dependent current of a photodiode. A small bias voltage derived to the op amp's non-inverting input so that the output will not go in saturation in the absence of input current. The photocurrent which needs to be amplified is applied to the inverting input, causing the output voltage to change according to the eq (3).
Iin is input photo current, Rf is feedback resistor. Cf is Feedback capacitor is used to maintain stability when gain changes.
TIA as shown in figure 3 is designed for low optical signal amplification. It is designed such that it will not lead to saturation for high strength of optical signal. So microcontroller based auto gain selection facility is provided. To provide different gains of 250, 750, 1000 and 4000, the values of the feedback resistances and capacitances are calculated by using eq. (4) and (5) respectively. The Rf values were selected for this design, one to ensure a range of maximum output voltage, with low-intensity absorbed signals and to ensure that the output voltage does not exceed the analog to digital convertor (ADC) reference voltage, with the highest intensity signals. The range of output generated is between few mV to 2.5V (ADC reference voltage) where, Vo (max) is maximum output voltage, Vo (min) is minimum output voltage, Iin (max) is maximum input current of photodiode.
A capacitor is placed in parallel with feedback resistor Rf to stabilize the transimpedance amplifier. The value of feedback capacitor is calculated using eq. (5).
where, CT is the total capacitance of the photodiode and op-amp, fGBW is a gain bandwidth product of op-amp

Selection of Microcontroller
MSP 432P401R micro-controller of Texas Instruments is selected because it has in-build 14-bit SAR ADC. It has low power Processor i.e active: 80 µA/MHz. It is used to select the gain as per the program fed to it.
The feedback resistors of TIA are connected to the channels of analog multiplexer which is interfaced with the precision microcontroller. As per channel selection program, specific feedback resistor is selected and absorbance is calculated. For different intensity of light, the absorbance is measured as per flowchart shown in figure 4. Initially the threshold voltages are fed to the microcontroller as largest value (Y) and smallest value (X) of the measured voltage. The output of transimpedence amplifier is compared with these threshold voltages. The initial reading of the incident light without filter is noted as P0. Then, as per selected filter the equivalent voltage for light after absorption is noted as P. The absorbance is calculated for each filter action as per formaula fed to it and it is displayed on LCD display.

Result
The front-end circuit of the semiautomatic blood diagnostic machine, as shown in figure 2 was designed, constructed and tested at different light intensities. The PCB for the same circuit was designed in Altium Software and the schematic is as shown in figure 5.  The performance of TIA was tested at different intensities of light and its output is compared with the transmission density step wedge film, i.e. absorber film available with 4 to 14 levels along with certificate as shown in figure 6.   Table 2 shows that the results observed in light intensity of 80Kcd/m 2 when the output of the TIA is given to the microcontroller.

Conclusion
Here, an ultra low signal TIA with auto-gain selector circuit is designed for blood diagnostic machine. The suitable TIA with auto gain facility is designed with selected photodiode for 300nm to 900nm wavelength which calculate absorbance precisely in the case of low optical signal. The front end circuit of the blood diagnostic machine is constructed and tested at different light intensities. Microcontroller MSP432P401R 32 BIT Arm Cortex 4 microcontroller with 14 bit inbuilt precision ADC is used to facilitate auto-gain selection, such that TIA is prevented to go into saturation. The experimental results showed that the designed TIA is stable and accurate up to gain 4000 at highest absorbance level. It is also observed that the photocurrent decreases as absorbance level increases. The photocurrent at the highest absorbance level is calculated which is approximately equal to16 µA. It is found that the absorbance measured with this circuit is up to the range of 3.5 on the absorbance scale from 80 to 130Kcd/m 2 . The results are found satisfactory with maximum error of 0.04 when compared with absorbance scale of transmission strip i.e. approximately 98.9% is achieved.