A portable ultrasonic device has been designed for the purpose of individual daily self-checking and early detection of breast cancer. In 2023, we have completed the design and setting-up of the hardware and associated software.

Ultrasound refers to the sound with a frequency above 20,000 Hertz (Hz) that is undetectable by the human ear. Medical ultrasound that is often called as sonography or diagnostic medical sonography uses much high frequencies between 1 and 20 megahertz (MHz) or even up to 75 MHz for diagnostic and therapeutic purposes.^1-3 By the detection of acoustic echo waves, ultrasound creates deeper real-time pictures or video of internal organs or soft tissues such as blood vessels than other light-based techniques because of the better penetration capabilities of ultrasound into solid tumors.⁴ When the ultrasonic longitudinal wave is transmitted into the body, reflections are generated from tissue interfaces with different acoustic properties, such as speed and density that can be recorded by the same transmitting transducer for the generation of diagnostic images. The medical application of ultrasound echo signals in combination with the implementation of statistic distribution analysis can reveal diverse structures of tissues and organs.⁵ In addition to mammography and MRI, ultrasound has become a major technique for breast cancer screening.^6-10 In order to help people with early detection of breast cancer, we take the advantage of ultrasound wave for the development of a portable and individually affordable device that can be used in regular daily self-checking.¹¹ A rubber model has been used for proof-of-principle demonstration.

Lots of ultrasonic systems have been developed and applied in clinical medicine.¹² There are mainly two types of medical ultrasound including diagnostic and therapeutic ultrasound. Diagnostic ultrasound can be further sub-divided into anatomical and functional ultrasound, which produces static images or dynamic information maps with the movement and velocity or other physical characteristics, respectively.¹³ Therapeutic ultrasound does not produce images but modify or destroy tissues such as moving or heating tissues, dissolving blood clots, and even delivering drugs to specific organs.¹⁴ It is aimed to destroy diseased or abnormal tissues such as tumors.¹⁵ The distinguished advantage of ultrasonic therapies is the non-invasive feature.¹⁶ Although there is a fundamental resolution limit resulting from the diffraction of sound wave, a super-resolution ultrasound Doppler imaging beyond the acoustic diffraction limit has been achieved by which the microvasculature can be detected with the aid of microbubbles and compounded plane-wave ultrasound transmissions.^1,17 To tackle with the problem of low temporal resolution that usually requires a large number of imaging frames, improved deconvolution and spatio-temporal-interframe-correlation based data acquisition have been developed.18 A diameter down to 41 μm, 5 times higher spatial resolution than the acoustic diffraction limit at 7.7 MHz, and a temporal resolution that allows for imaging vessels over cardiac motion have been reported.¹⁸ We have designed a dual mode portable ultrasonic device that is based on the A-mode ultrasound penetration and the near infrared irradiation with low cost but technologic advancements. It is in accordance with the proposed manganese dioxide nano immunomodulators that can in situ generate O2 in acidic tumor microenvironment. The oxygen nanobubbles may function as a contrast agent guiding for tumors in addition to the designed nano-immunomodulator function. We are describing the detailed design of the hardware, including the main controller module, the excitation and reception circuit of ultrasonic signals, echo processing and positioning calculation module.

The proposed portable ultrasonic device includes 3 major processes: (1) emission of ultrasound wave; (2) acoustic wave propagation. (3) echo detection. As shown in Figure 1, A-mode ultrasound is based on the reflection characteristics of ultrasound to acquire relevant information within tissues for diseases diagnosis. Reflection echoes are generated at interfaces that have different acoustic properties. When the ultrasound beam propagates in tissues and encounters adjacent media interfaces, an echo is generated and displayed in amplitudes on the oscilloscope screen. The larger the acoustic impedance difference between the two sides, the higher the amplitude of its echo wave. If ultrasound propagates in a uniform medium without any interfaces, the acoustic impedance difference is zero and the medium is anechoic. The physiological status can be assessed with the amplitude, size, shape, and position on the timeline of echo waves.

Figure 1. Ultrasound propagation and echo detection.

Detection of pulsed echoes is essential for ultrasound diagnosis and imaging. Pulse echo testing (pulse reflection) is the most commonly used technique in the field of ultrasound. A pulse wave, or a sine, triangular, and square wave with several cycles can be used for ultrasound device. Because the wave source vibrates for a very short time (usually on the order of microseconds), the amplitude can only exist for a short period of time (intermittent emission). The time differences can be used to extract the reflected ultrasound signals. The main workflow of A-type ultrasound device is described in Figure 2. Firstly, a short high-frequency signal is generated by the main controller. Then the high-frequency signal is amplified by the amplification circuit to form a pulse wave with a certain power, which drives the ultrasound probe to produce ultrasound. Ultrasound waves reflect when pass through different acoustic impedance interfaces. The reflected ultrasound waves are received by the probe and converted into electrical signals. The distance between the acoustic impedance interface and the probe can be calculated by the time when the echo reaches the probe.

Figure 2. Localization of masses based on echo time.

When the incident wave I propagates to the interface between medium 1 and medium 2, a portion of the sound wave T will transmit into medium 2, and another portion of the reflected wave R will re-enter medium 1 and propagate backwards. On the boundary, if the total displacement of each medium is equal, equation 1 is obtained.

ξ_T ,ξ_i and ξ_R represents the displacement of transmitted, incident, and reflected waves, respectively. Similarly, since the pressures on both sides of two media are equal, equation 2 is obtained.

P_T ,P_i and P_R are also potential function of the pressures, and their relationship with displacement is described in equation 3:

In which ρ and c represent the density and sound propagation velocity of the medium, respectively. Define . From the above formula, we obtain equation 4.

The acoustic impedance Z=ρc of the medium is defined here. From equations (1) and (3), we obtain equation 5 and 6.

Similarly, the similarity relationship between the pressure of incident sound waves and reflected sound waves can be obtained. The incident sound waves reflect a portion of their energy at the interface of the two media, and the proportion of reflected energy is related to the ratio of the acoustic impedance of the two media. For a plane boundary with a size much larger than wavelength λ, the reflection coefficient R is defined as the ratio of the amplitude of the sound wave reflected from the boundary to the amplitude of the incident sound wave, and the relationship is described as equation 7.

Similarly, the transmission coefficient T is equal to the ratio of the amplitude of the sound wave transmitted from the boundary to the amplitude of the incident wave.

According to equation (7), the larger the difference in acoustic impedance between the two media at the interface, the stronger the sound waves reflected from the interface, and the weaker the sound waves transmitted into the other interface.

The overall diagram and picture of the hardware based on A-mode ultrasound is shown in Figure 3. The main controller ESP32 and its peripheral circuits provide low voltage control signals to the ultrasonic excitation circuit through I/O pins. The low voltage control signal is not sufficient to drive the ultrasonic probe to generate ultrasound. The ultrasonic signal excitation circuit is designed to amplify the signal and the amplified signal drive the ultrasonic probe to generate ultrasound. Once the frequency of the ultrasonic signal is recognized, it will send a signal to the main controller. The time difference between the emission signal and the received signal is calculated by the main control panel based on the sound propagation speed. Tumors are localized from the data generated from the ultrasound array. The ESP32 main controller is connected to the phone and the location information can be sent to individuals. The infrared light generation module is designed for the clearance of engineered bacteria as well as tumors once the mission is completed.

Figure 3. The overall design of the hardware

The schematic diagram of the A-mode ultrasound unit is shown in Figure 4. Due to the fact that ultrasound examination requires the ultrasound probe to be tightly pressed against the object in order to obtain a good signal, we have designed a device that uses gears and sliders to push the ultrasound probe tightly against the object. The probe is connected with a sliding rheostat to push the probe forward and backward. A pressure sensor is used to determine whether the probe is tightly attached to the object. Based on the changes in resistance value of the sliding rheostat, we can calculate the relative position of the probe and the slider. In order to better fit the object, the probe is designed as a movable part. The angle sensor records the angle of the probe relative to the connecting rod, and proceed to the next step. With this unit, we can obtain parameters such as ultrasonic echo time, angle relative to the connecting rod, and the distance of the slider movement. The schematic diagram and the picture of the A-mode ultrasound unit are shown in Figure 4.

Figure 4. The schematic diagram and the picture of the A-mode ultrasound unit

In order to better mimic the shape of the object, A-mode ultrasound array is shown in Figure 5. In a plane, the curve of the shell can be considered as a parabola, and the position of each ultrasonic unit is perpendicular to the tangent at that point of the parabola. The position coordinates of the ultrasonic probe can be calculated by distances. The edge position information of the lump can be obtained from four ultrasound units. In the case of three-dimensional space, a three-dimensional ultrasound array is formed by orthogonalizing two planar ultrasound units. The edge position is extended from the plane to space, and the line connecting the edge position information can roughly form the shape of the tumor.

Figure 5. A-mode ultrasound array

In this module, an ultrasonic excitation circuit is designed. We adopt a direct drive method by which a high-power switch is used to directly supply power to the ultrasonic transducer. A DC power supply and six square wave signals are emitted from the I/O port of ESP32. As shown in Figure 6, they are amplified into driving signals through TC4426 driver.

Figure 6. The generation of excitation signal. Blue: TC4426 output signal. Yellow: input signal.

Ultrasonic probe matching circuit has been designed. The piezoelectric transducer has a static capacitor C₀ and a static inductance L₀. In the resonant state of the transducer, there is a phase angle^ᶲ between the voltage V_RL and the current I_RL on the transducer.， Because of the presence of^ᶲ, the output power cannot reach its maximum value. In order to make the voltage V_RL on the transducer be in phase with the current I_RL, it is necessary to parallel a phase canceling inductive reactance (or capacitive reactance) on the transducer.⁶ Ultrasonic transducers can be described using the Butterworth Van Dyke (BVD) model in Figure 7 (A), where C₀ and Rs represent the equivalent capacitance and radiation or mechanical losses, respectively. Ls and Cs simulate the resonant performance of the transducer. When an inductor is connected in series to the transducer and the inductor L satisfies equation 9, the reactance of the matching inductor can be eliminated from the reactance of the static capacitor.

Several filter circuits have been designed and established for echo receiving. The electrical signal from the probe contains a lot of noise components that cannot be directly processed. It should be filtered, reshaped, and amplified to extract the echo signal. Figure 7(B) shows an RC low-pass filter that can effectively suppress high-frequency components when multiple signals of different frequencies are mixed together. Figure 7 (C) shows a high-pass filter with a significant suppression effect on low-frequency signals. The effective ultrasonic echo signal frequency is around 40 KHZ and the noise spectrum is widely distributed. Therefore, it is necessary to simultaneously remove the noise that deviates from the main lobe. By seting appropriate parameters for the two filters in series, a bandpass filter can be formed. The cutoff frequency of the bandpass filter is described in equation 10 and Figure 7(D).

In which R, C and f represents the resistance value, the capacitance value, and the frequency at which the output signal is reduced to 0.707 times the maximum value, respectively.

Figure 7. Electronic circuits. (A) Butterworth Van Dyke model. (B) Low pass filter. (C) High pass filter. (D) Bandpass filter

Figure 8 (A-C) show the input signals at 10KHZ, 40KHZ and 100KHZ frequencies. It is shown that the signal at 40 KHZ frequency is less suppressed by using the bandpass filter. The final obtained signal is obtained with a bandpass filter with a center frequency of 40kHz.

Figure 8. Input signals at different frequencies. (A) 10 KHZ. (B) 40 KHZ. (C) 100 KHZ.

Operational amplifier circuit has been designed and established. A dual operational amplifier chip LM358 has been chosen. It includes two independent and compensated operational amplifiers. Under recommended operating conditions, the power supply current is independent of the power supply voltage. Figure 9 (A) shows the electronic circuit and Figure 9 (B) shows the established amplifier circuit can amplify a 20 mV sine signal by approximately 25 times. This amplifier circuit has been used to test signals from the ultrasound probe. Figure 9 (C) and (D) represent the original signal and the amplified signal, respectively. It was found that the probe signal can be efficiently amplified with the established circuit.

Figure 9. Operational amplifier circuit. (A) Electronic circuit. (B) Amplified 20 mV signal. (C) Original probe signal. (D) Amplified probe signal.

Detection circuit has been designed and established. A preamplifier Cx20106a is used in the detection circuit. It consists of a preamplifier, limiting amplifier, bandpass filter, detector, integrator, and shaping circuit. The circuit connection is shown in Figure 10 (A) by which a falling pulse at pin 7 can be generated when pin 1 has a 40kHz signal input as shown in Figure 10 (B). It means the echo can be received.

Figure 10. Detection circuit. (A) Electronic circuit. (B) Detection of the echo.

The main controller circuit has been developed with ESP 32 and other associated circuit as shown in Figure 11. It is designed for the control and the communication among different units. The localization of the rubber object should be calculated from the collected echo time. In the near future, more complicated algorithm will be developed to compute echo time, localize masses and construct ultrasound imaging with more complicated ultrasound array.

Figure 11. ESP 32 board.

We have completed one related computer program for the control of ultrasound control (Ultrasound Control Code, UCC). We hope make some contributions to the IGEM community and those computer programs is open for download.

Please Click here to download UCC program.

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