A method for signal enhancement and restoration in biological experiments of a terahertz near-field system

Abstract

The application discloses a signal enhancement and restoration method for a terahertz near-field system biological test, belongs to the field of terahertz near-field imaging, and mainly solves the problems of small terahertz signal value and unclear internal imaging of a terahertz near-field system in biological sample imaging. First, it is judged whether the signal can be restored; second, vibration is performed to realize signal restoration; and finally, mechanical treatment is performed to realize signal enhancement. The method effectively solves the problem of gradually small signal in biological imaging of the terahertz near-field system. The method has the characteristics of simple operation and cost saving, and is favorable for popularization and application of the terahertz near-field system in biological imaging.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of terahertz near-field system imaging, and particularly relates to a signal enhancement and repair method for biological experiments of a terahertz near-field system. BACKGROUND

[0002] The terahertz near-field imaging system is based on an atomic force microscope system and is composed of a terahertz source, a terahertz light path, a parabolic mirror, a probe platform and the like. Terahertz waves are emitted by the terahertz source, pass through the terahertz light path, are focused by the parabolic mirror to the front end of the probe needle in the atomic force microscope, the probe needle is above the sample, the terahertz waves reflected by the probe carry the near-field information of the sample and return to the terahertz light path through the parabolic mirror, and then reach the signal processing system of the atomic force microscope to realize the high-resolution imaging function of the terahertz near field. The imaging accuracy is generally nanometer-level accuracy, and the accuracy can be tens of nanometers or even a few nanometers.

[0003] When the terahertz near-field system imaging is used for biological experiments, the front end of the probe needle needs to be placed above the biological sample with high water content, and the nanometer-level needle tip at the lower end of the probe will contact the surface of the biological sample by using interatomic force. Due to the high water content of the biological sample, the surface is not uniform, such as the liquid solidification of the fixing agent during cell fixation and the different heights of the internal biological tissue sections. The probe tip will adsorb water or biological tissue containing water, which directly causes the electric field of the metal probe needle tip to change, affects the transmission of the terahertz near-field signal, and causes the effective signal value of the terahertz near-field system to become smaller. When imaging, the internal image has low clarity or even no clarity due to weak signal, which leads to poor internal imaging effect of the terahertz near-field imaging system. When this problem occurs, the current solution is to replace the probe of the terahertz near-field system, re-adjust the signal light path, and finally select a probe with small adsorption force. This method is easy to damage the nanometer-level probe needle tip, has high cost, and is complicated and time-consuming to operate, which limits the application of the terahertz near-field system in biological imaging. SUMMARY

[0004] The summary of the present application is to remove the attachments on the probe needle tip by adopting probe vibration and combining with specific process methods such as mechanical friction of the probe needle tip when it is judged that there are attachments on the position of the metal probe needle tip, so as to increase the signal at the probe needle tip and achieve the purpose of signal enhancement and repair. A signal enhancement and repair method for biological experiments of a terahertz near-field system is provided.

[0005] In order to solve the problem that the terahertz near-field system is in the biological sample imaging, the nanometer needle tip and the biological sample take the atomic force to contact, the water and the water-containing tissue of the biological sample are adsorbed at the needle tip part, the signal transmission at the needle tip is affected, the terahertz signal value is small, and the internal imaging is not clear, the present application mainly aims at removing the adhesion under the condition that the probe needle tip is not damaged and the needle tip exists the adhesion, and then the purpose of improving the signal is achieved. The adhesion is removed by changing the probe vibration amplitude and increasing the mechanical friction force, and finally the signal enhancement and repair are realized. The present application provides a probe signal repair method, effectively increases the service life of the probe in the biological imaging of the terahertz near-field system, avoids the cost increase and complex operation caused by frequent probe replacement, realizes the enhancement and repair of the terahertz signal, and provides a specific process for the popularization of the terahertz near-field system in the biological sample internal imaging.

[0006] The technical scheme adopted by the present application to solve the technical problems is: a signal enhancement and repair method for a terahertz near-field system in biological test, aiming at the phenomenon that the probe tip adsorbs the adhesion and affects the terahertz signal to be weak in the biological sample imaging of the terahertz near-field system, first, judging whether the needle tip is damaged and not repairable and the needle tip adsorbs the adhesion, observing the morphology by an optical microscope; second, realizing signal repair by vibration, increasing the recorded voltage of the probe to suddenly increase the probe amplitude, removing the adhesion to realize the repair of the terahertz signal; and finally, realizing signal increase by mechanical treatment, adjusting the voltage to control the distance between the needle tip and the non-biological sample, reducing the distance to scan in a large range and increase the friction force between the needle tips, removing the adhesion to realize the enhancement of the terahertz signal.

[0007] The present application has the advantages that the terahertz signal can be repaired and enhanced without replacing the probe, the cost increase and complex operation caused by replacing the probe can be avoided, the working life of one probe in the biological test is increased, a specific process is provided for the popularization of the terahertz near-field system in the biological sample internal imaging, and the operation is simple and the cost is low. BRIEF DESCRIPTION OF DRAWINGS

[0008] The present application will be further described below in combination with the drawings and examples.

[0009] Figure 1 is a schematic diagram of the probe under an optical microscope;

[0010] Figure 2 is a schematic diagram of the vibration of the probe under excitation voltage;

[0011] Figure 3 is a schematic diagram of the interatomic van der Waals force.

[0012] Among them Figure 1 In the figure, 1 is a probe, and 2 is a sample. DETAILED DESCRIPTION

[0013] In order to make the objectives, technical solutions, and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are intended only to illustrate the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other. To achieve the above-mentioned objectives, the present invention adopts the following technical solutions.

[0014] A method for signal enhancement and repair in biological experiments using a terahertz near-field system addresses the problem of atomic contact between the nanoprobe tip and the biological sample during terahertz near-field imaging. This problem can cause water and hydrated tissue in the biological sample to adsorb onto the nanoprobe tip, impacting signal transmission at the tip and resulting in a reduced terahertz signal and unclear internal imaging. To address the problem of probe tip adsorption affecting terahertz signal degradation, a specific process for removing adsorbed material from the probe tip without replacing the probe was investigated. The method involves three steps: step 1, identification and repair; step 2, vibration repair; and step 3, mechanical treatment. Ultimately, this method removes adsorbed material from the probe tip, achieving terahertz signal enhancement and repair.

[0015] Step 1: Determine whether it is repairable. Use the optical microscope in the terahertz near-field system to observe the changes at the tip of the nanoprobe. The microscope magnification is rotated to the maximum position. The probe 1 is located in the middle of the optical imaging position, and the biological sample 2 is below the probe tip. Figure 1 Fine-tune the focus to ensure the needle tip is as clear as possible for easier evaluation. Use optical imaging to determine if the needle tip is damaged, such as by deformation, tilt, or bending. If there is no damage and only an opaque attachment is present at the tip, it can be removed for signal repair and enhancement. Observe the location and shape of the attachment at the needle tip to facilitate comparison during subsequent operations.

[0016] Step 2: Repair the vibration signal. In the terahertz near-field system, perform needle withdrawal to separate the probe tip from the biological sample. Set the tapping excitation voltage of the probe. The magnitude of the excitation voltage mainly controls the vibration amplitude of the needle tip, such as Figure 2 As shown, changes in voltage will cause the probe's vibration position to change. For example, during normal operation, the excitation voltage is 0.05 volts. During repair, the voltage should be amplified by at least 20 times. Here, the voltage is increased by 20 times 0.05 volts to 1 volt, causing the probe to vibrate. Simultaneously, observe the image of the probe tip and the attached object under the optical microscope for changes. Repeat this process three or more times. Then, after automatically advancing the probe, observe the change in the terahertz signal value. Generally, small attachments are removed, and the terahertz signal can be restored.

[0017] Step 3: Increase the mechanical signal. Move the probe to a substrate without biological samples. The substrate is usually a conductive substrate such as gold, coated silicon wafer, graphene, etc., which should be higher than the biological sample. The voltage is 0 volts when the needle is inserted automatically. Figure 3 Then set the scanning range and perform a large-scale scan. The large-scale scan is 20-50 times the normal scanning range. For example, if the normal scanning range is 20 microns, then the large-scale scan is at least 20 times 400 microns, which is 20 times of 20 microns. The probe is moved quickly. Then single-step the needle, with a voltage of around -50 volts. Figure 3 In the medium repulsive force range, the distance between the probe tip and the substrate is reduced, increasing the friction between them as the probe tip moves. A wide range of rapid scans is performed in four directions: front, back, left, and right, repeating at least three times in each direction. During the scan, the shape of the attachment and changes in the terahertz signal value are simultaneously observed under the microscope, especially changes in the signal value. If movement in a certain direction (front, back, left, or right) increases the signal value, the number of movements in that direction is increased. Generally, large attachments are already removed through mechanical processing, thus achieving both attachment removal and signal enhancement.

[0018] This method removes deposits from the probe tip through three steps: detection repair, vibration repair, and mechanical treatment. This method enhances and repairs the terahertz signal, effectively resolving the problem of gradually diminishing signals during terahertz near-field biological imaging. Repairing and enhancing the terahertz signal without replacing the probe avoids the increased cost and complexities of probe replacement, extending the probe's lifespan in biological experiments. This provides a simple, low-cost, and specific process for promoting the use of terahertz near-field systems for imaging within biological samples.

Claims

1. A method for signal enhancement and repair in biological experiments using a terahertz near-field system, characterized in that: To address the phenomenon that adsorption on the probe tip weakens the terahertz signal, a method for removing adsorbents on the probe tip without replacing the probe is proposed. The method includes the following three steps: Step 1: Determine whether the needle tip is irreparably damaged and whether there is any adsorbent on the needle tip by observing its morphology under an optical microscope; Step 2: Next, vibration is performed to achieve signal repair. By increasing the excitation voltage of the probe, the probe amplitude is suddenly increased, and the attachment is removed to achieve terahertz signal repair; Step 3: Mechanical processing is performed to increase the signal. The distance between the needle tip and the non-biological sample is controlled by adjusting the voltage. The probe position is moved to the substrate position without the biological sample. The distance is reduced to perform a large-scale rapid scan to increase the friction between the needle tip and remove the attachments to enhance the terahertz signal. The specific implementation method of step 1 is that the probe is located in the middle position of the microscope optical imaging, the probe is not damaged in the optical imaging, and an opaque attachment appears on the tip of the probe; The specific implementation method of step 2 is that the tapping excitation voltage of the probe is more than 20 times the normal excitation voltage value, and the above operation is repeated more than 3 times; The specific implementation method of step 3 is to perform a large-range scan, which is 20-50 times the normal scanning range; the voltage is -50 volts; scan in four directions of front, back, left, and right, and repeat each direction more than 3 times.

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