Non-contact ultrasonic pipette and method of pipetting

Abstract

The application discloses a non-contact ultrasonic liquid transfer gun and a liquid transfer method thereof. The liquid transfer gun comprises a shell, a piezoelectric focusing ultrasonic probe, semiconductor lasers, a control circuit, a power supply and a trigger button. The piezoelectric focusing ultrasonic probe, the control circuit, the power supply and the trigger button are sequentially arranged along the inner wall of the shell from the liquid taking end. The semiconductor lasers comprise two and are symmetrically distributed on both sides of the front end surface of the piezoelectric focusing ultrasonic probe. The power supply is connected with the control circuit for power supply. The trigger button is connected with the control circuit to control the two semiconductor lasers to complete optical positioning, drive the piezoelectric focusing ultrasonic probe to generate an ultrasonic field and realize near-field acoustic levitation of liquid drops on a super-hydrophobic surface. The application can realize non-contact control of liquid drops on a super-hydrophobic surface and solve the problems of traditional contact type liquid transfer guns, such as complicated operation caused by frequent replacement of the gun head, gun head consumption, reagent waste and sample pollution.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pipette, in particular to a non-contact ultrasonic pipette and a pipetting method thereof. BACKGROUND

[0002] The pipette can realize accurate sample adding or transferring, and is widely used in clinical examination, pharmaceutical, life science research, environmental protection detection, animal and plant inspection and quarantine research and the like. The traditional pipette needs to install a pipette tip for liquid suction or discharge at the inlet and outlet of the pipette. In order to avoid sample pollution in the repeated operation process, the pipette tip can only be used once and must be replaced in time after use, which causes a large consumption of the pipette tip. Moreover, in daily use, there is a situation that a liquid film is left on the inner wall of the pipette tip, which causes a large waste of valuable samples and environmental pollution when the pipette tip is discarded. In addition, the contact liquid taking is prone to sample cross contamination. Therefore, it is of great significance to design a non-contact ultrasonic pipette to reduce the consumption of the pipette tip and the waste of reagents and avoid reagent pollution.

[0003] The ultrasonic wave has been widely used in biochemical analysis and detection fields, such as ultrasonic cleaning, sample enrichment and cell sorting. In the aspect of droplet manipulation, the current main methods are based on surface acoustic wave and standing wave acoustic field suspension technology, which can realize the motion control of droplets in two-dimensional plane and three-dimensional space. However, the existing surface acoustic wave and standing wave acoustic field suspension technology has the defects of complex hardware circuit system, poor stability of acoustic field gradient and complex programming of droplet manipulation, which is difficult to be widely applied to the basic pipetting operation in conventional biochemical experiments. SUMMARY

[0004] In view of the above problems, the present application provides a non-contact ultrasonic pipette and a pipetting method thereof, which can realize non-contact pipetting in cooperation with a super-hydrophobic surface, and has no special requirements on the electromagnetic properties of the droplet, is simple to operate, and can effectively reduce or avoid the problems of large consumption of the pipette tip of the traditional pipette, easy waste and pollution of reagents.

[0005] The technical solution adopted by the present application to solve the above technical problems is as follows:

[0006] On the one hand, a non-contact ultrasonic pipette comprises a shell, a piezoelectric focusing ultrasonic probe, a semiconductor laser, a control circuit, a power supply and a trigger button; the piezoelectric focusing ultrasonic probe, the control circuit, the power supply and the trigger button are sequentially arranged along the inner wall of the shell from the liquid taking end; the semiconductor laser comprises two parts and is symmetrically distributed on both sides of the front end surface of the piezoelectric focusing ultrasonic probe; the power supply is connected with the control circuit for power supply; the trigger button is connected with the control circuit to control the two semiconductor lasers to complete light positioning, drive the piezoelectric focusing ultrasonic probe to generate an ultrasonic field, and realize near-field acoustic suspension of a droplet on a super-hydrophobic surface.

[0007] Preferably, the piezoelectric focusing ultrasonic probe, the control circuit, the power supply and the trigger button are sequentially arranged along the axial direction of the inner wall of the shell from the liquid taking end.

[0008] Preferably, the front end surface of the piezoelectric focusing ultrasonic probe is a concave spherical surface with a spherical radius of 10-30 mm; the piezoelectric focusing ultrasonic probe has a cylindrical structure as a whole with a radius of 3-8 mm and a focal length of 20-40 mm.

[0009] Preferably, the two semiconductor lasers are small-power visible semiconductor lasers emitting red or green light; the beams of the two semiconductor lasers intersect at the focal point of the piezoelectric focusing ultrasonic probe.

[0010] Preferably, the control circuit comprises a single-key bistable switch module, an ultrasonic probe driving oscillation module, a power amplifier module and a laser driver module; the single-key bistable switch module is connected to the trigger button, and the ultrasonic probe driving oscillation module or the ultrasonic probe driving oscillation module is controlled to work based on the pressing time of the trigger button; the power amplifier module is connected to the ultrasonic probe driving oscillation module to amplify the oscillation signal output by the ultrasonic probe driving oscillation module and drive the piezoelectric focusing ultrasonic probe to work; the laser driver module is connected to the semiconductor laser to drive the semiconductor laser to work.

[0011] Preferably, the single-key bistable switch module comprises a single-key bistable switch, a first relay and a second relay; the trigger button is connected to the trigger end of the single-key bistable switch, the first relay is connected to the first output end and the power supply end of the single-key bistable switch, and the second relay is connected to the second output end and the power supply end of the single-key bistable switch; one pressing gives the control circuit one pulse signal through the single-key bistable switch, specifically, the first pressing controls the first relay to be on, the semiconductor laser is powered on to emit light, the second pressing controls the first relay to be off, the semiconductor laser is powered off, the third pressing controls the second relay to be on, the piezoelectric focusing ultrasonic probe is powered on, and the fourth pressing controls the second relay to be off, the piezoelectric focusing ultrasonic probe is powered off.

[0012] Preferably, the ultrasonic probe driving oscillation module comprises a 555 timer, and when the single-key bistable switch controls the second relay to be on, the oscillation frequency is adjusted by adjusting the resistance and capacitance values; the power amplifier module comprises a triode, and the oscillation signal output by the 555 timer is amplified through the triode to drive the piezoelectric focusing ultrasonic probe to work.

[0013] Preferably, the laser driver module comprises a voltage stabilizer, and when the single-key bistable switch controls the first relay to be on, the voltage stabilizer provides a stable driving voltage for the diode of the semiconductor laser.

[0014] Preferably, the power supply includes a 12V lithium battery, the positive electrode of the lithium battery is connected to the positive electrode contact piece, the negative electrode of the lithium battery is connected to the negative electrode contact piece, and the positive electrode contact piece and the negative electrode contact piece are connected to the positive and negative input ends of the control circuit, respectively.

[0015] In another aspect, a non-contact ultrasonic pipetting method based on the non-contact ultrasonic pipetting gun comprises:

[0016] Pressing the trigger button for a first preset time turns on the power supply, the control circuit and the two semiconductor lasers, and the light beams of the two semiconductor lasers converge, if two separate light spots are formed on the super-hydrophobic surface, the distance and angle of the pipetting gun to the super-hydrophobic surface are further adjusted until the two light beams of the laser converge into one point at the droplet, and the positioning is completed.

[0017] Pressing the trigger button again for a first preset time turns off the two semiconductor lasers.

[0018] Pressing the trigger button for a second preset time turns on the piezoelectric focusing ultrasonic probe to generate an ultrasonic field, and realizes near-field acoustic levitation of the droplet on the super-hydrophobic surface.

[0019] Moving the pipetting gun, the droplet is suspended and moved with the pipetting gun under the action of the gradient force, and when the droplet moves to a suitable position, the trigger button is pressed again for a second preset time, the piezoelectric focusing ultrasonic probe is turned off to release the droplet, and one non-contact ultrasonic pipetting operation is completed.

[0020] The beneficial effects of the present application are:

[0021] (1) The present application realizes the light-assisted positioning of the acoustic field focus by sending a trigger signal to the trigger button to control the semiconductor laser, and realizes the non-contact pipetting of the droplet on the super-hydrophobic surface by sending a trigger signal to the trigger button to control the piezoelectric focusing ultrasonic probe, compared with the traditional pipetting gun, a large number of gun heads are not consumed, and the waste and pollution of reagents are effectively avoided.

[0022] (2) The present application receives the pressing information of the trigger button through the bistable switch circuit, controls the connection and disconnection of different relays according to the pressing time, and further controls the working of the semiconductor laser or the piezoelectric focusing ultrasonic probe. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 It is a front view of the overall structure of the non-contact ultrasonic pipetting gun of the embodiment of the present application.

[0024] Figure 2 It is a control circuit principle block diagram in the non-contact ultrasonic pipetting gun of the embodiment of the present application.

[0025] Figure 3The circuit schematic diagram of the single-key bistable switch of the embodiment of the present application;

[0026] Figure 4 The circuit schematic diagram of the piezoelectric focusing ultrasonic probe driving oscillation module and power amplification module of the embodiment of the present application;

[0027] Figure 5 The circuit schematic diagram of the semiconductor laser driving module of the embodiment of the present application;

[0028] Figure 6 The working flowchart of the non-contact ultrasonic liquid moving gun of the embodiment of the present application;

[0029] In the figure: 1-trigger button; 2-power supply; 3-control circuit; 4-piezoelectric focusing ultrasonic probe; 5-semiconductor laser; 6-housing; 7-ultrasonic wave, 8-laser beam, 9-liquid droplet, 10-ultrahydrophobic surface. DETAILED DESCRIPTION

[0030] The specific embodiments of the present application are described in detail below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present application, and are not used to limit the present application.

[0031] Embodiment 1

[0032] Referring to Figure 1 The non-contact ultrasonic liquid moving gun of the present application includes a trigger button 1, a power supply 2, a control circuit 3, a piezoelectric focusing ultrasonic probe 4, semiconductor lasers 5, and a housing 6. The piezoelectric focusing ultrasonic probe 4, the control circuit 3, the power supply 2, and the trigger button 1 are sequentially arranged along the inner wall of the housing 6 from the liquid taking end. The semiconductor lasers 5 include two and are symmetrically distributed on both sides of the front end surface of the piezoelectric focusing ultrasonic probe 4. The power supply 2 is connected to the control circuit 3 for power supply. The trigger button 1 is connected to the control circuit 3 to control the two semiconductor lasers 5 to complete optical positioning and drive the piezoelectric focusing ultrasonic probe 4 to generate an ultrasonic field, thereby realizing near-field acoustic levitation of liquid droplets on an ultrahydrophobic surface.

[0033] Specifically, the piezoelectric focusing ultrasonic probe 4, the control circuit 3, the power supply 2, and the trigger button 1 are sequentially arranged along the axial direction of the inner wall of the housing 6 from the liquid taking end.

[0034] In this embodiment, the power supply 2 includes a 12V lithium battery pack. The positive electrode of the lithium battery in the lithium battery pack is connected to a positive electrode connecting tab, and the negative electrode of the lithium battery is connected to a negative electrode connecting tab. The positive electrode connecting tab and the negative electrode connecting tab are respectively connected to the positive and negative input terminals of the control circuit 3.

[0035] Referring to Figure 2As shown, the control circuit 3 includes a single key bistable switch module 31, an ultrasonic probe drive oscillation module 32, a power amplifier module 33 and a laser drive module 34. The control circuit 3 is provided with a terminal connected with the power supply 2, a terminal connected with the semiconductor laser 5, a terminal connected with the piezoelectric focusing ultrasonic probe 4 and a single key bistable switch module 31 connected with the trigger button 1.

[0036] Specifically, the single key bistable switch module 31 includes a single key bistable switch KDA, a first relay KS1 and a second relay KS2. The trigger button 1 is a spring type trigger button, which is connected with the single key bistable switch KDA. The principle of the single key bistable switch module 31 is shown in Figure 3 As shown, it is connected with the control circuit 3 via the first relay KS1 and the second relay KS2. Each time the trigger button 1 is pressed, different pulse signals can be given to the control circuit 3 according to the pressing time. In this embodiment, when the pressing time is within 0.5 seconds, the first relay KS1 is controlled to be on / off. Pressing once turns it on (first pressing), and pressing again turns it off (second pressing), and the cycle continues. When the pressing time lasts more than 0.5 seconds, the second relay KS2 is controlled to be on / off. Pressing once turns it on (third pressing), and pressing again turns it off (fourth pressing), and the cycle continues. The first pressing (pressing time less than 0.5 seconds) makes the laser power on to emit light, the second pressing (pressing time less than 0.5 seconds) makes the laser power off, the third pressing (pressing time more than 0.5 seconds) makes the piezoelectric ceramic focusing ultrasonic probe power on, and the fourth pressing (pressing time more than 0.5 seconds) makes the piezoelectric ceramic focusing ultrasonic probe 4 power off.

[0037] Referring to Figure 4 As shown, the ultrasonic probe drive oscillation module 32 includes a 555 timer. When the switch K2 is turned on by the second relay KS2, the oscillation frequency is related to the resistance R1, R2 and the capacitance C1 in the circuit, and the oscillation frequency The frequency of the ultrasonic wave can be adjusted by adjusting the resistance and capacitance values.

[0038] Specifically, the switch K2 is the output terminal of the second relay KS2. The input terminal of the second relay KS2 is connected with the trigger button 1 (see Figure 3 When the trigger button 1 receives a pulse signal with a pressing time more than 0.5 seconds, the second relay KS2 controls the on / off of its output terminal K2, thereby realizing the functions of controlling the piezoelectric focusing ultrasonic probe drive oscillation module 32 and the power amplifier module circuit 33.

[0039] Referring to Figure 4 As shown, the power amplifier module 33 includes a high-power triode Q1, which amplifies the oscillation signal output by the 555 timer, thereby driving the piezoelectric ceramic focusing ultrasonic probe to work.

[0040] Referring to Figure 5 As shown, the laser driver module 34 includes a LM317 adjustable voltage regulator, which can provide a stable driving voltage for the red or green laser diode when the switch K1 is turned on by the first relay KS1, and the output stable driving voltage is related to R5 and R6, and the output voltage Vout = 1.25*(1+R5 / R6), and the adjustable voltage output can be achieved by adjusting the resistance of the potentiometer R5.

[0041] Specifically, the switch K1 is the output terminal of the first relay KS1, the input terminal of the first relay KS1 is connected to the trigger button 1 (see Figure 3 As shown), and the output terminal is connected to the switch K1. When the trigger button 1 receives a pulse signal with a pressing time less than 0.5 seconds for the first time, the signal will be input to the first relay KS1 from the input terminal, so that the first relay KS1 is turned on, and then the output terminal K1 is turned on, so that the semiconductor laser driver module 34 circuit is turned on. When the trigger button 1 receives a pulse signal with a pressing time less than 0.5 seconds for the second time, the signal will be input to the first relay KS1 from the input terminal, so that the first relay KS1 output terminal K1 is turned off, and then the semiconductor laser driver module circuit is turned off.

[0042] In this embodiment, the piezoelectric focusing ultrasonic probe 4 is a cylindrical body with a radius of 3-8 mm, the piezoelectric ceramic transducer head is a spherical concave surface with a radius of 10-30 mm, the focal length is 20-40 mm, and the tail is provided with a wiring terminal connected to the control circuit 3. Based on the inverse piezoelectric effect of the piezoelectric transducer (i.e. Figure 2 , the spherical concave surface piezoelectric ceramic vibration is driven to form a focused sound field, so as to generate an acoustic pressure gradient force to realize near-field acoustic levitation of liquid droplets on a super-hydrophobic surface.

[0043] In this embodiment, the piezoelectric ceramic transducer head is provided as a spherical concave surface, which has the effect of making the ultrasonic waves emitted from the concave spherical surface converge at the center of the sphere after being energized, so that the liquid droplets to be removed receive the maximum lift at the center of the sphere. The spherical radius of 10-30 mm has the effect of allowing different pipetting heights to be selected according to the concave spherical radius in actual use. In addition, the piezoelectric focusing ultrasonic probe is provided as a cylindrical structure, which has the effect of facilitating the design of a handheld cylindrical structure. Let the concave spherical radius be a mm, the cylindrical radius be b mm, and the focal length be c mm. The relationship among them can be expressed as a*a = b*b + c*c.

[0044] In this embodiment, the semiconductor laser 5 is a small power visible light semiconductor laser 5 emitting red or green light, the number is 2, symmetrically arranged on both sides of the front end surface of the piezoelectric focusing ultrasonic probe 4, so that the light beams emitted by the two semiconductor lasers 5 intersect at the acoustic focal point position, thereby realizing the light positioning function. Specifically, when the semiconductor laser 5 is powered on, the light beams of the two semiconductor lasers 5 converge. If there are two separate light spots on the super-hydrophobic surface, it indicates that the distance between the pipette and the liquid surface is too far or too close, and the height or angle of the pipette needs to be adjusted until the two light beams converge into a point at the liquid droplet, and the acoustic wave focuses on the liquid droplet position.

[0045] Specifically, the head of the housing 6 of the pipette is a thin cylindrical shape, and the inner wall of the head is provided with semiconductor laser clamping grooves, piezoelectric focusing ultrasonic probe clamping grooves and the like. The tail is provided with a hanging hook, and the inner wall of the tail is provided with control circuit clamping grooves, 12V lithium battery pack clamping grooves and the like. The inside of the housing 6 is integrally provided with a through wiring slot.

[0046] Embodiment 2

[0047] Referring to Figure 6 The embodiment is a non-contact ultrasonic pipetting method of the pipette of embodiment 1. By pressing the trigger button 1 once (the pressing time is less than 0.5 seconds), the power supply 2, the control circuit 3 and the semiconductor laser 5 are turned on, and the laser beams 8 of the two semiconductor lasers 5 converge. If two separate light spots are formed on the super-hydrophobic surface 10, it indicates that the distance and angle of the pipette to the super-hydrophobic surface 10 need to be adjusted until the two light beams of the semiconductor laser 5 converge into a point at the liquid droplet 9, that is, the positioning is completed. At this time, press the trigger button 1 again (the pressing time is less than 0.5 seconds), and the semiconductor laser 5 is powered off. At this time, press the trigger button 1 (the pressing time is greater than 0.5 seconds), and the piezoelectric focusing ultrasonic probe 4 is powered on to generate ultrasonic waves 7, so that the near-field acoustic levitation of the liquid droplet 9 on the super-hydrophobic surface 10 can be realized. At this time, move the pipette, and the liquid droplet 9 will move with the pipette due to the action of the acoustic pressure gradient force. When the liquid droplet 9 moves to the appropriate position, press the trigger button 1 again (the pressing time is greater than 0.5 seconds), and the piezoelectric focusing ultrasonic probe 4 is powered off to release the liquid droplet 9, thereby completing a non-contact ultrasonic pipetting operation.

[0048] In summary, the light-assisted positioning of the acoustic field focal point can be realized by sending a trigger signal to the semiconductor laser 5 through the trigger button 1, and the non-contact pipetting of the liquid droplet 9 on the super-hydrophobic surface 10 can be realized by sending a trigger signal to the piezoelectric focusing ultrasonic probe 4 through the trigger button 1. Compared with the traditional pipette, a large number of gun heads do not need to be consumed, and the waste and pollution of reagents can be effectively avoided.

[0049] The above examples are only used to illustrate the technical solutions of the present application, and are not intended to limit the present application; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that the technical solutions recorded in the foregoing examples can be modified, or some or all of the technical features can be replaced by equivalents; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A non-contact ultrasonic pipette, characterized in that, The device includes a housing, a piezoelectric focused ultrasound probe, a semiconductor laser, a control circuit, a power supply, and a trigger button. The piezoelectric focused ultrasound probe, control circuit, power supply, and trigger button are arranged sequentially along the inner wall of the housing, starting from the liquid extraction end. The semiconductor laser includes two components, symmetrically distributed on both sides of the front end face of the piezoelectric focused ultrasound probe. The power supply is connected to the control circuit to provide power. The trigger button is connected to the control circuit to control the two semiconductor lasers to complete optical positioning and drive the piezoelectric focused ultrasound probe to generate an ultrasonic field, thereby achieving near-field acoustic levitation of droplets on a superhydrophobic surface.

2. The non-contact ultrasonic pipette according to claim 1, characterized in that, The piezoelectric focused ultrasound probe, control circuit, power supply, and trigger button are arranged sequentially along the axial direction of the inner wall of the housing, starting from the liquid extraction end.

3. The non-contact ultrasonic pipette according to claim 1, characterized in that, The front end face of the piezoelectric focused ultrasound probe is a concave spherical surface with a radius of 10-30 mm; the piezoelectric focused ultrasound probe has an overall cylindrical structure with a radius of 3-8 mm and a focal length of 20-40 mm.

4. The non-contact ultrasonic pipette according to claim 1, characterized in that, The two semiconductor lasers are low-power visible light semiconductor lasers that emit red or green light; the beams of the two semiconductor lasers intersect at the focal point of the piezoelectric focusing ultrasound probe.

5. The non-contact ultrasonic pipette according to claim 1, characterized in that, The control circuit includes a single-button bistable switch module, an ultrasonic probe drive oscillation module, a power amplifier module, and a laser drive module. The single-button bistable switch module is connected to the trigger button and controls the operation of the ultrasonic probe drive oscillation module based on the pressing time of the trigger button. The power amplifier module is connected to the ultrasonic probe drive oscillation module and amplifies the oscillation signal output by the ultrasonic probe drive oscillation module to drive the piezoelectric focusing ultrasonic probe. The laser drive module is connected to a semiconductor laser to drive the semiconductor laser.

6. The non-contact ultrasonic pipette according to claim 5, characterized in that, The single-button bistable switch module includes a single-button bistable switch, a first relay, and a second relay. The trigger button is connected to the trigger terminal of the single-button bistable switch. The first relay is connected to the first output terminal and the power supply terminal of the single-button bistable switch. The second relay is connected to the second output terminal and the power supply terminal of the single-button bistable switch. Each press sends a pulse signal to the control circuit through the single-button bistable switch. Specifically, the first press controls the first relay to open, energizing the semiconductor laser; the second press controls the first relay to close, de-energizing the semiconductor laser; the third press controls the second relay to open, energizing the piezoelectric focused ultrasound probe; and the fourth press controls the second relay to close, de-energizing the piezoelectric focused ultrasound probe.

7. The non-contact ultrasonic pipette according to claim 6, characterized in that, The ultrasonic probe drive oscillation module includes a 555 timer. When the second relay is turned on by a single-button bistable switch, the oscillation frequency is adjusted by adjusting the resistor and capacitor values. The power amplification module includes a transistor, which amplifies the oscillation signal output by the 555 timer to drive the piezoelectric focused ultrasonic probe.

8. The non-contact ultrasonic pipette according to claim 6, characterized in that, The laser driving module includes a voltage regulator. When the single-button bistable switch controls the first relay to turn on, the voltage regulator provides a stable driving voltage for the diode of the semiconductor laser.

9. The non-contact ultrasonic pipette according to claim 1, characterized in that, The power supply includes a 12V lithium battery pack. The positive terminal of the lithium battery in the lithium battery pack is connected to a positive terminal connector, and the negative terminal of the lithium battery is connected to a negative terminal connector. The positive terminal connector and the negative terminal connector are respectively connected to the positive and negative input terminals of the control circuit.

10. A pipetting method using a non-contact ultrasonic pipette, characterized in that, The non-contact ultrasonic pipette according to any one of claims 1 to 9 includes: Press the trigger button for the first preset time to connect the power supply, control circuit and two semiconductor lasers. The beams of the two semiconductor lasers converge. If two separate light spots are formed on the superhydrophobic surface, further adjust the distance and angle of the pipette to the superhydrophobic surface until the two laser beams converge at the droplet to a single point to complete the positioning. Press the trigger button again for the first preset time, and the two semiconductor lasers will be powered off. Press the trigger button for the second preset time, and the piezoelectric focused ultrasonic probe will be powered on to generate an ultrasonic field, achieving near-field acoustic levitation of droplets on a superhydrophobic surface; As the pipette is moved, the droplet is subjected to a gradient force and moves in the air with the pipette. When the droplet moves to the appropriate position, the trigger button is pressed again for the second preset time. The piezoelectric focused ultrasonic probe is then de-energized and releases the droplet, completing one non-contact ultrasonic pipetting operation.

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