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Chapter 5: Readout system development

5.2 Readout system automation

5.2.6 Excitation and readout

Since the Lab On Chip approach aims to realize portable, cheap and easy to use devices for point of care diagnostics, it is useful to miniaturize also the control interface. Of course, in prototyping phase it is fine to use very expensive and configurable instrumentation to characterize the sample and to optimize the parameters, but at the end, simpler and cheaper systems, also with pre-imposed optimal and fixed values for structures excitation and readout are preferable. In this framework, with the final aim to feed the structure with a sinusoidal current, but without using a standard and expensive laboratory generator, we exploited two different options.

94

Figure 5.12: Sinewave obtained with ICL8038 (a) and specific picture of the device.

The first one is to find into the market some prototypal low-cost signal generator, but there are few available at the moment, since the ones made on board with integrated circuits and passive components are usually simple TTL oscillators. After a deep research we’ve found the ICL 8038 (Figure 5.12), which is very cheap (few euros) and not very cumbersome (several centimeters in planar view and few in section).

The advantage of this device is the analogic output with programmable frequency in the range 10 𝐻𝑧 – 450 𝑘𝐻𝑧. It can be set up through some screws to define the signal amplitude (12 𝑉 – 15 𝑉) and frequency, but also to change the shape of the signal from triangular to rectangular or sine wave. The disadvantages are the impossibility of obtaining always the same signal on different devices, since it depends on the skills of the operator and to further reduce its dimensions.

The second option is based on a digital approach: the use of STM32 Nucleo also as a voltage source (Figure 5.13) in parallel with its control function over the system described above. This way of feeding the PHE sensors is a little different respect to the one employed during the characterization phase, since in that case the current was maintained constant in amplitude and the structures show an AMR in longitudinal direction. Basically, a current generator is a voltage source having a feedback network that let the voltage on the terminals change according to the measured resistance of the charge in real time.

(a) (b)

95 To avoid this further complexity, we checked that there is no appreciable difference in the planar Hall effect measured on our structures while changing the source from current to voltage, of course with the same working point at zero field, because the AMR effect poorly changes the resistance of the device and, consequently the current density remains almost constant.

Figure 5.13: Sinewave obtained with STM32 Nucleo L152RE.

Since this platform has several pins able to provide voltage in the range GND – 5 V, we let it calculate and store a “sine table” on start-up and then to set this different values on an output pin continuously, which is connected with the PHE based sensors’ array on one side (the other is grounded). The advantages of this approach are the chance to have the excitation “for free”

into the device, since the wave is driven by an already present module and the versatility of the amplitude. The bigger disadvantage is that the frequency is strongly related to the sine wave resolution: after a code optimization, we were able to obtain a wave of 1.2 𝑘𝐻𝑧 with 100 points for period, which fell down to 120 𝐻𝑧 if we construct a 1000 points sine table.

Regarding the readout, in literature there are reported some open source electronics sketch for making a home-made lock-in amplifier89 with few tenths of euros of integrated amplifiers available on the market and standard components as resistors and capacitance, as shown in the electrical scheme reported Figure 5.14. Specifically, it consists of a pre-amplification stage, where the signal coming from a BNC cable pass through an operational amplifier which gain depends on the selected feedback resistance. Then, its output passes through a demodulator, to be multiplied by a reference signal to choose the frequency to be filtered. The signal passes through a low-pass filter, where the cut-off frequency is chosen by connecting a specific

96 capacitor to system ground and further amplified with constant gain before arriving at the output BNC. Starting from this reference, it’s possible to easily produce a lock-in amplifier to be integrated in the final device with the other components after some simplification: SMA connections (instead of BNC) and the removal of switching between resistors (in first stage) and capacitance (in low pass filter), but choosing the optimized parameters for sensitivity and time constant employed during the measurement with our instrument SR830.

Figure 5.14: Electrical scheme of the device described in 89.

Considering the actual need of automation, the proposed solution can easily be integrated in a single portable device, because it’s possible to industrialize the sensing circuit’s production through some microelectronic supplier able to produce and assemble it on a single printed board. Furthermore, the STM32 Nucleo has the chance to provide the system with many voltage outputs that can be easily used for driving a stepper motor able to move the magnets needed for the aggregation and introduction chambers and also to control some fluidics valves. The magnetic field control is also integrated by exploiting the Oersted field for this goal (patent pending).

Conclusions and future works

First results of this PhD research work were the fabrication of state of the art magnetoresistive structures with high performances. Specifically, GMR based junctions with magnetoresistive ratio 𝐺𝑀𝑅 = 4.1% and sensitivity 𝑆 = 6 %/𝑚𝑇, TMR junctions showing the value 𝑇𝑀𝑅 = 103% and 𝑆 = 11.8 %/𝑚𝑇 and PHE based sensors with a constructed magnetoresistive ratio of 𝑃𝐻𝑅 =100% (which is not indicative in this case, but in any case the signal excursion was of 64 𝑚Ω) with sensitivity 𝑆 = 47 %/𝑚𝑇 (8 𝜇𝑉/𝑂𝑒). The comparison among these parameters led us to choose the PHE structures as the best candidates for our purpose. Furthermore, the microfluidics simulation performed led us to choose a good micro-channels arrangement useful for the dynamic sensing of magnetic nanoparticles freely diffusing above the sensing area of a device containing and array of such a structure. The realization of the platform containing the developed modules showed encouraging results during the preliminary tests performed and should be carried on obtaining the final complete and integrated device as the output of the European project MADIA with the other modules developed throughout the consortium. The dynamic concept developed can change the actual state of the art about the biosensing, since it has several advantages with respect to the standard detection method, allowing easier and faster devices fabrication, less dependence on statistical events and the perfect reusability of the device after one measurement. Further enhancements can be achieved with the optimization of the array geometry by changing the pitch of the sensors and eventually moving to a circular layout instead of a linear one and with the introduction of reference structures to take into account the changes in the environmental condition, always having a baseline of the response without the analyte to be revealed.

The parallel exploitation of the Electrochemical Impedance technique, appliable to a range of analyte from particles, peptides, DNA strands until bacteria and cells, to the sensing of tau protein opened up to us large perspectives for several applications, leading to a publication already available and two more actually in preparation.

98 The development of integrated interface for the readout, performed during the 6 months internship at the laboratories of the industrial partner STMicroelectronics, led us to obtain a versatile platform to characterize different types of Lab On Chip devices. Notably, the good agreement between the calculated coupling between the signal lines with the experimental one measured with the LCR meter suggested us to employ that simulation model to further optimize the interface or to develop a new one with solid basis before proceeding in the fabrication, avoiding to waste time and money for this purpose. Finally, the employment of the microcontroller STM32 Nucleo L152 RE and the multiplexer MAXIM Integrated MAX14661 with their evaluation boards and the consequent development of the driving script in both C++

and LabView allowed us to obtain a powerful platform for fast prototyping the implementation of several interfaces to be applied for unexploited sensing technologies and then the realization of the corresponding integrated device.

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