WO2023212860A1

WO2023212860A1 - Terahertz near-field audio modulation and demodulation nano-probe array system and method, and storage medium

Info

Publication number: WO2023212860A1
Application number: PCT/CN2022/090954
Authority: WO
Inventors: 常天英; 魏东山; 崔洪亮
Original assignee: 中国科学院深圳先进技术研究院
Priority date: 2022-05-05
Filing date: 2022-05-05
Publication date: 2023-11-09

Abstract

A terahertz near-field audio modulation and demodulation nano-probe array system and method, and a storage medium. On the basis of a terahertz near-field audio modulation and demodulation nano-probe array, the system mixes terahertz wave signals, and demodulates the terahertz wave signals to acquire biomacromolecule information. By means of a terahertz near-field audio modulation and demodulation nano-probe array, fast and dynamic microscopic imaging of biomacromolecules under testing can be realized.

Description

Terahertz near-field acoustic frequency modulation and demodulation nanoprobe array system, method and storage medium

Technical field

The invention relates to the field of microscopic imaging, and in particular to a terahertz near-field acoustic frequency modulation and demodulation nanoprobe array system and method and a storage medium.

Background technique

Terahertz waves have great application potential in the field of biomedical spectral imaging due to their fingerprint spectrum of biological macromolecules, good penetration, and no ionization damage, and have become a research hotspot at home and abroad. For conventional far-field terahertz imaging based on traditional lens focusing, since the terahertz spot is much larger than the size of biomolecules, the physical diffraction limit causes a serious scale mismatch. What is obtained by far-field detection is the average effect of the entire spot covering biomolecules. At present, nanoprobes are used to super-diffract terahertz waves and focus them on the probe tip, forming a terahertz local enhanced field that is equivalent to the curvature radius of the probe tip. By controlling the curvature radius of the probe tip, the focused spot size reaches the nanometer level. , obtain super-diffraction focused terahertz waves and achieve nanoscale imaging spatial resolution, that is, terahertz near-field imaging.

However, current research related to terahertz near-field imaging focuses on static or slow imaging. Even with sufficient spatial resolution, it can only image specific states of interaction between biological macromolecules and cannot show the relationship between terahertz radiation and biological systems. All the information that the interaction process can reveal.

Contents of the invention

In order to solve the problems existing in the existing technology, the present invention provides a terahertz near-field acoustic frequency modulation and demodulation nanoprobe array system and method and a storage medium. The technical solution of the present invention is as follows.

A nanoprobe array device, including a directional coupler, a radio frequency mixer, a subharmonic mixer, an IQ mixer, a lock-in amplifier, a signal generator and a nanoprobe array;

The directional coupler and the subharmonic mixer cooperate with each other to transmit the terahertz wave signal scattered back by the nanoprobe array to the IQ mixer; the radio frequency mixer is used to transmit the vibration source signal to the IQ mixer; the IQ mixer is used to mix the terahertz wave signal; the lock-in amplifier demodulates the terahertz wave signal to obtain biological macromolecule information.

Preferably, the signal of the first local oscillator source is input into the directional coupler after power amplification and frequency multiplication, and is output to the nanoprobe array through the directional coupler; the terahertz frequency scattered back by the nanoprobe array The wave signal enters the RF end of the sub-harmonic mixer through the directional coupler; the signal of the second local oscillator source enters the LO end of the sub-harmonic mixer after power amplification and frequency multiplication;

And, the signals of the first local oscillator source and the second local oscillator source are respectively input to the radio frequency mixer, and the output of the radio frequency mixer is input to the LO end of the IQ mixer after power amplification and frequency multiplication. ; The RF end of the IQ mixer is connected to the IF end of the sub-harmonic mixer; the IQ mixer is used to achieve terahertz wave signal mixing; the quadrature phase component of the IQ mixer and in-phase components are input into the lock-in amplifier respectively.

Preferably, the nanoprobe array includes several signal generators, and each signal generator generates vertical vibration modulation signals at different frequencies.

Preferably, the lock-in amplifier reference input is provided by a signal generator, and the number of lock-in amplifier reference inputs matches the number of signal generators.

Preferably, the probe length and tip curvature radius of each nanoprobe of the linear array are the same.

A terahertz near-field imaging system, the terahertz near-field dynamic imaging system includes the above-mentioned nanoprobe array device.

A terahertz near-field audio modulation and demodulation method based on the above-mentioned nanoprobe array device, including:

The nanoprobe connected to the tuning fork is vibrated with nanometer amplitude at acoustic or ultrasonic frequency, and the modulation frequency range and frequency interval are selected, and the near-field signal is modulated using the mechanical vibration of the nanoprobe;

The detected near-field signal is phase-locked and amplified at the fundamental frequency or high harmonic frequency of the mechanical vibration, so that the unmodulated background signal scattered back from the tuning fork and the probe cone body is discarded;

The nanoprobe array is synchronously scanned with the terahertz near-field detection time period as the scanning period, so that the nanoprobe array reads the terahertz near-field signal detected by the detector every time it steps on the stage.

Preferably, the spatial coordinates of the nanoprobe and the detected terahertz signal are stored as the same node data, which is used as the terahertz near-field detection time period of a nanoprobe array imaging pixel.

Preferably, individual nanoprobes are labeled by identifying the terahertz near-field scattering signal from the nanoprobe to achieve localized demodulation of the terahertz scattering signal of each nanoprobe.

A storage medium includes a computer program that executes the above terahertz near-field audio modulation and demodulation method when running.

Compared with the existing technology, the beneficial technical effect of the present invention is that: the present invention is based on the terahertz near-field acoustic frequency modulation and demodulation nanoprobe array, and on the basis of breaking through the diffraction limit and having nanoscale spatial resolution, it improves the imaging speed and achieves Rapid dynamic microscopy imaging of tested biological macromolecules.

Description of drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required to be used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present application and therefore do not It should be regarded as a limitation of the scope. For those of ordinary skill in the art, other relevant drawings can be obtained based on these drawings without exerting creative efforts.

Figure 1 is a schematic diagram of a terahertz near-field imaging system based on a nanoprobe array.

Figure 2 is a schematic diagram of the nanoprobe array structure.

Figure 3 is a schematic diagram of the probe array arrangement and scanning.

Figure 4 is a schematic diagram of the probe signal demodulation process.

Figure 5 is a schematic diagram of signal phase-locked amplification.

Detailed ways

In order to make the purpose, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only These are part of the embodiments of this application, but not all of them.

As shown in Figure 1, this embodiment provides a terahertz near-field acoustic frequency modulation and demodulation nanoprobe array system and its imaging system, including a local oscillator source, a beam splitter, a power amplifier, several frequency multipliers, and directional coupling amplifier, horn antenna, off-axis parabolic mirror, RF mixer, subharmonic mixer, IO mixer, lock-in amplifier, signal generator.

The local oscillator sources S1 and S2 both use phase-locked sources as low-frequency transmission signals. For example, the signal frequency of the phase-locked source S1 is 27.5GHz. In order to obtain higher output power, a high-gain power amplifier is used to amplify the transmit power of the signal source before frequency multiplication; the transmitted signal passes through a four-fold After the frequency is combined with a frequency doubler, the frequency becomes a 220GHz point frequency signal, which is used as the radio frequency (RF) signal of the system. It is finally emitted by the nanoprobe array through the directional coupler, horn antenna and off-axis parabolic mirror. The nanoprobe array scatters The terahertz wave signal carrying biological macromolecule information enters the RF input end of the subharmonic mixer through the directional coupler. Phase-locked source S2 serves as the system local oscillator signal generator with a frequency of 27.475GHz. After passing through the power amplifier, it passes through a quadruple frequency as a local oscillator signal and enters the sub-harmonic mixer.

The schematic diagram of the nanoprobe array structure is shown in Figure 2. Each nanoprobe of the linear array structure has the same length and tip curvature radius. For example, the radius of curvature of the tip is about 10 nm, and the distance between two adjacent nanoprobes is controlled in the range of 20-60 nm. Use a focused ion beam to modify the structure or radius of curvature of the probe to obtain a probe tip with a radius of curvature of approximately 100 nm; then use vacuum coating or thermal evaporation metallization to process the tip to prepare a probe array with a radius of curvature of approximately 10 nm to achieve Terahertz near-field imaging at the single-molecule level.

Part of the output of the two phase-locked sources enters the two RF ends of the RF mixer respectively. After the intermediate frequency output passes through the power amplifier, it is changed to 219.8GHz by a quadruple frequency and a double frequency multiplier, and then enters the I-Q mixing The local oscillator input end is mixed with the terahertz wave signal scattered back by the nanoprobe array.

Exemplarily, the nanoprobe array is set to eight, and the eight-channel signal generator gives vertical vibration modulation signals of different frequencies. The vertical vibration modulation frequencies are respectively set to Ω _n =10KHz, 11KHz...17KHz, n=1. ,2...7, the interval is 1KHz, then the I and Q outputs of the IQ mixer contain DC signals and harmonic components of Ω _n , which enter the I and Q input terminals of the eight-way lock-in amplifier respectively; the eight-way lock-in amplifier corresponds to The reference inputs are respectively provided by the above-mentioned eight signal generators, so that the IQ demodulation of the biological macromolecule information obtained by the eight nanoprobes corresponding to the modulation frequencies can be realized simultaneously.

This embodiment provides a terahertz near-field acoustic frequency modulation and demodulation nanoprobe array method, which includes: modulating N linear probe arrays. Use a lock-in amplifier to perform lock-in amplification of the detected near-field signal at the fundamental frequency of mechanical vibration or high-order harmonic nΩ (n=2, 3, 4...) frequency, thereby discarding the unmodulated slave probe Strong background signals scattered back from the surroundings such as tuning forks and probe conical bodies. Before phase-locked amplification, the Michelson interferometer in the terahertz optical path module is also used for interference amplification to improve detection sensitivity.

Signal demodulation of nanolinear multiprobe arrays. In order to demodulate the terahertz scattering signal of each nanoprobe, the natural vibration frequency identification of the tuning fork probe system is used to determine the terahertz wave scattered from the nth nanoprobe, and the terahertz wave is demodulated through the vibration frequency and its harmonics Near field signal. The natural frequency of the tuning fork is used to give the nanoprobe an acoustic frequency modulation vibration signal to cause it to vibrate up and down, thereby achieving corresponding modulation of different probes by vibration signals of different frequencies.

For example, the nanoprobe connected to the tuning fork is vibrated with nanometer amplitude at the acoustic or ultrasonic frequency Ωn. The natural resonant frequency of a tuning-fork nanoprobe is typically between 10kHz and 30kHz, with enough room for dozens or hundreds of individual resonant frequencies and enough frequency difference between adjacent frequencies to avoid crosstalk. For example, you can choose 10 tuning fork nanoprobes at 10kHz, 11kHz,...19kHz to form an array of 10 elements. Among them, ΔΩ=1kHz is the frequency interval between adjacent channels, and each channel corresponds to a single tuning fork nanoprobe. After selecting the modulation frequency range and spacing, the near-field signal can be modulated using the mechanical vibration of the probe. For the control of the nanoprobe, it is planned to use a motor to drive the probe to move in the Z direction with an accuracy of less than 10 nanometers and a stroke of 10 microns, so as to ensure safe and effective contact between the nanoprobe and the sample.

The synchronization control of probe array arrangement scanning is shown in Figure 3. It is realized through the cooperative control of software and hardware. The hardware timing is controlled by software so that the nanoprobe array steps one step on the stage, that is, the terahertz near-field signal detected by the corresponding detector is read; at the same time, in order to reduce the This terahertz signal is the result of phase-locked amplification through the up and down vibration of the nanoprobe due to the interference of the small probe's tapered body and the scattered signal of the tuning fork. Finally, the spatial coordinates of the nanoprobe and the detected terahertz signal are regarded as the same Node data is stored as a time period for terahertz near-field detection of an array of imaging pixels. After completing this series of actions, the next time period is entered through software control to detect the next array of pixels. Considering that there is a spacing of m*20 (m=1,2,3) nanometers between the tips of two adjacent nanoprobes, (m-1) more intersections are required when scanning each row or column. Scan to complete a panoramic scan of an entire row or column. The multi-probe synchronously controlled cross-scanning method enables complete panoramic scanning of the entire row or column without omission.

Due to the physical spacing of the probes, cross scanning needs to be set up to complete a panoramic scan of the entire row or column without missing any traces. Label individual nanoprobes by identifying different modulation frequencies of the terahertz near-field scattering signal from the nanoprobe, thereby achieving positional demodulation of the terahertz scattering signal of each nanoprobe; using synchronously controlled probe array arrangement Scan so that the entire row or column can be scanned without blind spots.

As shown in Figure 4-5, taking one of the modulation frequencies Ω as an example, the signal processing process is as follows:

hypothesis

represents the incident field signal emitted by the nanoprobe,

represents the backscattered field signal, E _n is the near-field signal, then

where eta is the reflection coefficient of the detected sample; F _m is the Fourier coefficient of the harmonic component,

|F _m |and

are the amplitude and phase of the Fourier coefficient respectively; ω _i is the frequency of the terahertz wave (as shown in Figure 1, which is 220GHz); θ ₀ is the phase of the incident terahertz wave; θ ₁ is the phase of the scattered terahertz wave.

Inevitably, the signal reflected back to the directional coupler includes not only the near-field signal received by the probe, but also the backscattered signal reflected by the tip and sample surface, so the signal entering the RF end of the subharmonic mixer can Expressed as E _RF =E _n +E _b , specifically:

Let E _LO represent the signal entering the local oscillator end of the subharmonic mixer,

Then the subharmonic mixer output E _IF can be expressed as

It can be seen that the output signal of the subharmonic mixer includes two frequency components ω _i -2ω _r and ω _i -2ω _r +mΩ; ω _r is the signal frequency entering the local oscillator end of the subharmonic mixer (such as Figure 1, which is 109.95GHz). In order to eliminate useless frequency component signals, the harmonic mixer output enters the RF end of the IQ mixer for further mixing. Since the local oscillator input of the IQ mixer

θ ₃ is the phase difference between the outputs of the two phase-locked sources, then the mixing signal E _if can be expressed as

After filtering out the DC component, E _if only contains the AC component of Ω harmonics, which can be expressed as

in,

F _m is the Fourier coefficient of the harmonic component,

|F _m |and

are the amplitude and phase of the Fourier coefficients respectively, which are determined by the complex dielectric properties of the sample and are the near-field signal amplitude and phase information that need to be demodulated.

set up

Then its two orthogonal outputs E _IF-i and E _IF-Q can be expressed as

Enter the I and Q input terminals of the lock-in amplifier respectively. Assuming that the initial phase of the reference input of the lock-in amplifier is zero, it can be expressed as

After phase-locked amplification processing, the outputs are respectively

In order to obtain the amplitude and phase of the lock-in amplifier input signal, a phase-locked loop (PLL) is designed at the reference input end of the lock-in amplifier to rotate the phase of the reference input signal by 90° to generate two orthogonal reference signals, which are respectively with The two input signals are multiplied together. Therefore, the m-order Ω frequency signal is phase-locked and demodulated, and the two orthogonal signals output are:

After phase-locked amplification processing, the corresponding amplitude and phase information can be obtained from its output signal as follows:

Ultimately, the required amplitude and phase information is obtained from the above formula:

This embodiment also provides a storage medium, including a computer program. When the computer program is run, the terahertz near-field audio modulation and demodulation method of this embodiment is executed.

This embodiment uses an audio frequency modulation and demodulation nanoprobe array device that combines a nanoprobe array with a fast scanning mechanism, combined with terahertz all-solid-state emission and reception coherent detection, completely getting rid of the limitations of the terahertz source and detector on the imaging speed, and improving It has improved the terahertz near-field imaging speed and met the requirements of real-time observation of the dynamic speed of interactions between biological macromolecules.

The above-mentioned embodiments are only specific implementation modes of the present application, and are used to illustrate the technical solutions of the present application, but not to limit them. The protection scope of the present application is not limited thereto, although the present application has been carried out with reference to the foregoing embodiments. Detailed description: Those of ordinary skill in the art should understand that any person familiar with the art can still make modifications to the technical solutions recorded in the foregoing embodiments or can easily think of changes within the technical scope disclosed in this application. Or make equivalent substitutions for some of the technical features; however, these modifications, changes or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present application. All are covered by the protection scope of this application. Therefore, the protection scope of this application should be subject to the protection scope of the claims.

Claims

A nanoprobe array device, characterized by including a directional coupler, a radio frequency mixer, a subharmonic mixer, an IQ mixer, a lock-in amplifier, a signal generator and a nanoprobe array;

The directional coupler and the subharmonic mixer cooperate with each other to transmit the terahertz wave signal scattered back by the nanoprobe array to the IQ mixer; the radio frequency mixer is used to transmit the vibration source signal to the IQ mixer; the IQ mixer is used to mix the terahertz wave signal; the lock-in amplifier demodulates the terahertz wave signal to obtain biological macromolecule information.
The nanoprobe array device according to claim 1, characterized in that, the signal of the first local oscillator source is input into the directional coupler after power amplification and frequency multiplication, and is output to the nanoprobe via the directional coupler. Needle array; the terahertz wave signal scattered back by the nanoprobe array enters the RF end of the subharmonic mixer through the directional coupler; the signal of the second local oscillator source enters after power amplification and frequency multiplication The LO terminal of the sub-harmonic mixer;

And, the signals of the first local oscillator source and the second local oscillator source are respectively input to the radio frequency mixer, and the output of the radio frequency mixer is input to the LO end of the IQ mixer after power amplification and frequency multiplication. ; The RF end of the IQ mixer is connected to the IF end of the sub-harmonic mixer; the IQ mixer is used to achieve terahertz wave signal mixing; the quadrature phase component of the IQ mixer and in-phase components are input into the lock-in amplifier respectively.
The nanoprobe array device according to claim 2, wherein the nanoprobe array includes a plurality of signal generators, and each signal generator generates vertical vibration modulation signals at different frequencies.
The nanoprobe array device according to claim 3, wherein the lock-in amplifier reference input is provided by a signal generator, and the number of reference inputs of the lock-in amplifier matches the number of signal generators.
The nanoprobe array device according to claim 4, wherein the probe length and tip curvature radius of each nanoprobe of the linear array are the same.
A terahertz near-field imaging system, characterized in that the terahertz near-field dynamic imaging system includes the nanoprobe array device according to any one of claims 1-5.
A terahertz near-field audio modulation and demodulation method based on the nanoprobe array device according to any one of claims 1 to 5, characterized in that it includes:

The nanoprobe connected to the tuning fork is vibrated with nanometer amplitude at acoustic or ultrasonic frequency, and the modulation frequency range and frequency interval are selected, and the near-field signal is modulated using the mechanical vibration of the nanoprobe;

The detected near-field signal is phase-locked and amplified at the fundamental frequency or higher harmonic frequency of the mechanical vibration, so that the unmodulated background signal scattered back from the tuning fork and the tapered body of the probe is discarded;

The nanoprobe array is synchronously scanned with the terahertz near-field detection time period as the scanning period, so that the nanoprobe array reads the terahertz near-field signal detected by the detector every time it steps on the stage.
The terahertz near-field audio modulation and demodulation method according to claim 7, characterized in that the spatial coordinates of the nanoprobe and the detected terahertz signal are stored as the same node data, thereby serving as a nanoprobe array Terahertz near-field detection time period for imaging pixels.
The terahertz near-field audio modulation and demodulation method according to claim 8, characterized in that, by identifying the terahertz near-field scattering signal from the nanoprobe, a single nanoprobe is marked to achieve the terahertz frequency of each nanoprobe. Localization demodulation of scattered signals.
A storage medium, characterized in that it includes a computer program that executes the terahertz near-field audio modulation and demodulation method described in any one of claims 7-9 when the computer program is run.