CN211591312U - Local modification biochemical molecular layer device for micro sensor - Google Patents
Local modification biochemical molecular layer device for micro sensor Download PDFInfo
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- CN211591312U CN211591312U CN201920368914.1U CN201920368914U CN211591312U CN 211591312 U CN211591312 U CN 211591312U CN 201920368914 U CN201920368914 U CN 201920368914U CN 211591312 U CN211591312 U CN 211591312U
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Abstract
The invention discloses a local modification biochemical molecular layer device for a micro-sensing device. The method is characterized in that: the same or different biochemical molecules are printed in a specific area by a micro-ink-jet method, and the surface of the sensor is subjected to local biochemical functional modification, so that the sensor meets the biochemical detection requirement. The device for local biochemical molecular layer modification comprises: the piezoelectric micro-nozzle can control the size of the printing liquid drop through voltage; the two cameras are used for three-dimensionally observing the positions of the micro-nozzles and the devices; the XY displacement table is used for placing the device on the workbench and moving in a horizontal plane along with the XY displacement table; a closed container for holding the printed biochemical molecules; an air pressure controller for adjusting the air pressure in the closed container; an XY displacement table data acquisition and control system, which can accurately control the XY direction movement displacement of the displacement table; the piezoelectric micro-nozzle control system is used for adjusting and controlling the size, the number and the state of printing liquid drops; an environmental control and measurement unit for measuring ambient environmental conditions.
Description
Technical Field
The invention belongs to the fields of semiconductors, biochemistry and engineering, and particularly relates to a device for locally modifying a biochemical molecular layer of a micro sensor.
Background
Along with the continuous expansion of the application of biochemical sensors in the fields of food, medicine, environment, process monitoring and the like[1-2]Higher requirements are put on the performance of biochemical sensors: high sensitivity, high stability, low cost, etc. In addition, the development of biochemical sensors presents the following trend according to the application requirements in the fields of disease diagnosis, food detection, environmental monitoring and the like: multi-functionalization: by using interference, three-dimensional high-speed stereo ink-jet[3]The self-assembly and other technologies develop multifunctional sensors, and as many sensors as possible are arranged on the smallest area as possible; and (3) miniaturization: the advent of various portable biochemical sensors has made it possible for people to diagnose diseases at home and to detect food directly on the market; integrate and intelligent: the sensor with the functions of detection, judgment, information processing and the like is developed to realize an automatic detection system, and a biochip system taking a chip as a structural characteristic realizes the integration and intellectualization of the detection process; low cost, high sensitivity, high accuracy and high stability: in order to go to the market, the cost of the biochemical sensor needs to be reduced, and the detection sensitivity, accuracy and stability need to be improved. Therefore, it is urgently needed to provide a micro sensor for detecting a biochemical molecule sensitive layerThe device for locally modifying the biochemical molecule layer of the piece.
The method aims at the problem that measurement errors are easily caused by adsorption and non-precise modification of a large number of biochemical molecules, and is always a research hotspot of high-sensitivity biochemical detection. The research on the aspect is not interrupted and is a technical difficulty which researchers always want to break through. For example, in 1995, t.thundat pioneered studies on the effect of surface adsorption on mechanical microcantilever frequency[4]. An Au film is evaporated on a V-shaped SiN micro-cantilever beam and is used for specifically adsorbing Hg vapor. Research shows that in addition to the change of the effective mass of the micro-cantilever in the specific adsorption process, the stiffness coefficient k of the V-shaped micro-cantilever is also changed under the action of surface stress, so that the resonance frequency is not reduced but continuously increased along with the extension of the reaction time. When the Au thin film is evaporated only on the portion of the surface of the micro-cantilever near the free end, the resonance frequency of the micro-cantilever is decreased as expected as the reaction time is prolonged, since the change of the stiffness coefficient k caused by the change of the surface stress after the reaction of Hg with Au is avoided. This finding is of great interest for research to eliminate large detection errors due to adsorption of large amounts of biochemical molecules and non-precise modification.
To date, research on biochemical sensors at home and abroad has made breakthrough progress, but many technical problems still exist, such as: when the biochemical sensor carries out large-area modification on biochemical molecules, large-area adsorption causes large measurement errors. Therefore, it is highly desirable to provide a locally modified bio-molecular layer device for micro-sensing devices. The method has the advantages of realizing high sensitivity, high stability and high-flux real-time detection on the biochemical molecules to be detected, realizing accurate printing and large-scale local modification on devices needing local modification and reducing the modification cost of trace biochemical molecules.
Reference to the literature
[1]C.N.Jayarajah and M.Thompson，″Signaling of transcriptionalchemistry in the on-line detection format，″Biosensors and Bioelectronics，vol.17，pp.159-171，2002.
[2]J.Kirsch，C.Siltanen，Q.Zhou，et al.，″Biosensor technology：recentadvances in threat agent detection and medicine，″Chemical Society Reviews，vol.42，pp.8733-68，2013.
[3]S.Salomon，T.
D.Dezest，et al.，″Arrays ofnanoelectromechanical biosensors functionalized by microcontact printing，″Nanotechnology，vol.23，p.495501，2012.
[4]T.Thundat E.A.Wachter，S.L.Sharp，et al.，″Detection of mercury vaporusing resonating microcantilevers，″Applied Physics Letters，vol.66，pp.1695-1697，1995.
SUMMERY OF THE UTILITY MODEL
Technical problem to be solved
In order to realize high sensitivity, high stability and high flux real-time detection of biochemical molecules to be detected and complete micro-precise modification of the biochemical molecules, technical breakthroughs are needed to be made in aspects of detection errors and the like of the biochemical molecules to be detected caused by adsorption and non-precise modification of a large number of biochemical molecules, and the invention provides a local modified biochemical molecular layer device for a micro sensor. In addition, the local modification is carried out by a micro ink-jet printing method, the modified area and the dosage can be accurately controlled, and the printing cost of the biochemical molecules is reduced by the local modification.
(II) technical scheme
In order to realize real-time high-sensitivity, high-stability and high-flux detection of molecules to be detected, realize accurate printing of devices needing local modification and reduce the modification cost of trace biochemical molecules, the invention provides a device for locally modifying biochemical molecule layers of a micro sensor, which is suitable for printing devices of various specifications and large-scale local modification schemes, and comprises the following steps: the piezoelectric micro-nozzle is used for printing the modified biochemical molecules; the air pressure controller is used for controlling and adjusting the air pressure in the closed container; the closed container is used for containing a solution containing biochemical molecules to be printed and is respectively connected with the air pressure controller and the piezoelectric micro-sprayer through the guide pipe to realize the liquid level control of the piezoelectric sprayer; the piezoelectric micro-nozzle control system is used for adjusting and controlling the size, the number and the state of printing liquid drops; a two-dimensional or three-dimensional table for placing the device to be printed and controlling the rotation of the device at the home position; the two-dimensional or three-dimensional workbench is placed on the XY displacement platform with high precision displacement and can move in a horizontal plane along with the XY displacement platform; an XY displacement table data acquisition and control system, which can accurately control the XY direction movement displacement of the displacement table through a software program; the two cameras are used for respectively observing the positions of the micro-nozzles and the devices in X and Y directions and the printing condition of liquid drops in a three-dimensional mode; and the environment control and measurement unit is used for controlling and detecting the appropriate environment conditions required in the biochemical molecule printing process, wherein the environment conditions comprise temperature and humidity.
Among the above-mentioned scheme, two cameras are fixed in on an inverted U type support through L type foot rest, and X direction is observed to one of them camera, and Y direction is observed to another camera, places a light source in two cameras just opposite orientation respectively and does benefit to the observation when observing, and two cameras can all carry out the perpendicular to horizontal plane internal rotation through revolution mechanic to and also can carry out regulation about and about to the camera through the displacement platform.
Among the above-mentioned scheme, airtight container and little shower nozzle together are fixed in a draw-in groove, the draw-in groove is fixed in same type of falling U support through the connecting piece again with the camera is the same, little shower nozzle just perpendicular to horizontal plane, and this connecting piece passes through the screw fixation and on a displacement bench, can carry out the removal about and, X direction camera and little shower nozzle are in the coplanar, and Y direction camera also need adjust to in the coplanar with little shower nozzle, be favorable to observing the printing state when printing more, adjust little shower nozzle from top to bottom can be in the observable within range of camera with the shower nozzle end, adjust little shower nozzle about and can adjust camera focus distance.
In the scheme, the printed device is arranged on a two-dimensional or three-dimensional workbench, and the surface to be printed is opposite to the micro-spray head.
In the above scheme, two-dimentional or three-dimensional workstation, through the screw fixation on XY displacement platform, and the workstation center is just to little shower nozzle, three-dimensional workstation's rotatable platform is clear glass, clear glass can improve luminance around the device, be favorable to the camera to observe more and the high definition is got looks, perhaps install a strobe light below two-dimensional workstation, make strobe light and little shower nozzle when adjusting the liquid drop or printing, high definition camera is on a line, be convenient for observe the liquid drop state, observe the surface printing condition by printing the device, and do benefit to the high definition and get for instance.
In the above scheme, the two-dimensional or three-dimensional workbench is provided with a waste liquid tank, and a culture dish is placed below the waste liquid tank and used for containing waste liquid generated when liquid drops are regulated, so that other areas of the device are prevented from being polluted.
In the scheme, the piezoelectric micro-nozzle control system controls and adjusts the state of liquid drops through a voltage signal loaded on the micro-nozzle, and controls the micro-nozzle to generate continuous liquid drops when constant voltage is loaded; when the pulse signal is loaded, the frequency and time of the pulse signal are used for controlling the interval time between the printing drop numbers, namely the printing frequency is controlled, the voltage amplitude is used for controlling the size of the printing drop, and the requirement of a printing device is met by adjusting the loading voltage signal.
In the scheme, the air pressure controller adopts positive air pressure and negative air pressure, the micro ink-jet device adopts positive air pressure to facilitate the printing of liquid drops when in normal work, and negative air pressure is used for suck back when the micro spray head is blocked, so that impurities are sucked out of the micro spray head; when the micro-spray head is cleaned, positive pressure and negative pressure are alternately combined for use.
In the scheme, the closed container is provided with a sealing cover which can be rotatably opened and screwed, when biochemical molecular liquid is filled and printed, the sealing cover is rotatably opened, the sealing cover is screwed after the liquid is filled, the sealing cover is provided with two guide pipes which are communicated with the closed container and the micro-spray head and the air pressure control system, wherein the guide pipe connected with the air pressure control system only extends to the bottle mouth of the sealing cover, and the other guide pipe connected with the micro-ink-jet printing system extends to the bottom of the closed container.
In the above scheme, the environment control and measurement unit is configured to control and detect a suitable environment condition required in the biochemical molecule printing process, where the environment condition includes temperature and humidity, the temperature is controlled by a heating plate, and the humidity is controlled by a humidifier.
The scheme comprises the following steps:
1) initializing the XY displacement table, and moving the center of the two-dimensional or three-dimensional workbench to a position right facing the micro-sprayer;
2) the environment control and measurement unit is used for accurately controlling and measuring the temperature and the humidity of the printing environment to achieve the most suitable conditions of the modified biochemical molecules;
3) filling biochemical molecular liquid to be printed into a closed container, enabling the pressure in the closed container to be far higher than the external pressure through an air pressure controller, enabling the biochemical molecules to flow through a micro-nozzle through a guide pipe to form continuous flow, closing the air pressure controller to enable the pressure in the closed container to be the same as the external pressure, enabling the liquid level at the tail end of the micro-nozzle to be static at the moment, and finely adjusting the liquid level to be parallel to the tail end of the micro-nozzle;
4) adjusting the position of the spray head, observing the spray head in the observation camera, taking a phase, and adjusting the distance between the camera and the spray head to adjust the focal length to obtain a clear image;
5) placing the surface of a printed device on a two-dimensional or three-dimensional workbench upwards, finely adjusting a camera and a nozzle to obtain a clear image, accurately moving the printed position to be opposite to the nozzle by controlling an XY displacement table, and adjusting the size and the number of droplets by setting voltage signal parameters to finish the printing modification process;
6) when large-scale array type local modification is carried out, the moving distance of each time and the printing drop number of each position can be set through a software program, and the large-scale local modification is quickly realized;
7) and taking out the printed device to complete the local decoration process.
(III) advantageous effects
According to the technical scheme, the beneficial effects of the invention are as follows:
1. the device for locally modifying the biochemical molecule layer for the micro sensor realizes local modification through the micro ink jet printing system, and realizes high-sensitivity, high-stability and high-flux real-time detection of biochemical markers on the premise of larger errors caused by large-scale biochemical molecule adsorption and non-precise modification detection.
2. According to the device for locally modifying the biochemical molecule layer for the micro sensor, provided by the invention, the biochemical molecule required for modification is sprayed in the region of the device to be modified by adopting micro ink-jet printing equipment for local modification, and the local modification is carried out by adopting a micro ink-jet printing method, so that the modification region and the dosage can be accurately controlled, and the modification cost of the biochemical molecule is greatly reduced.
3. The local modification biochemical molecular layer device for the micro sensor adopts micro ink jet printing equipment for local modification, and can select two working modes of single-drop printing and continuous printing, thereby realizing micro modification and large-scale local modification of devices with various specifications.
4. According to the device for locally modifying the biochemical molecular layer for the micro sensor, provided by the invention, the micro ink-jet printing equipment can accurately position the printing area by observing and adjusting the XY displacement table, the moving step length of the displacement table can be set on software of a control end as required, and the modified area is finally accurately positioned by adjusting the size step length.
5. According to the device for locally modifying the biochemical molecular layer for the micro sensor, the size of printing liquid drops can be controlled by adjusting the pressure intensity in the sealed bottle and the voltage loaded on the piezoelectric diaphragm of the micro sprayer, and the number of the printing liquid drops and the printing frequency can be controlled by the frequency and time of voltage pulses on the piezoelectric diaphragm in the micro sprayer.
6. The device for locally modifying the biochemical molecule layer for the micro sensor provided by the invention can respectively regulate and control the appropriate temperature and humidity environmental conditions required in the biochemical molecule printing process through the heating flat humidifier. Thereby providing a good environment for the whole modification process of the biochemical molecule layer.
Drawings
For the purposes of promoting a clear understanding of the objects, aspects and advantages of the invention, reference will now be made in detail to the following description, taken in conjunction with the accompanying drawings, wherein:
FIG. 1 is a schematic view of the overall structure of a micro-inkjet system of a device for locally modifying a biochemical molecular layer for a micro-sensor device according to the present invention;
FIG. 2 is a schematic structural diagram of an XY displacement stage and a three-dimensional or two-dimensional stage of the micro-inkjet printing apparatus according to the present invention;
FIG. 3 is a schematic structural diagram of a closed container and a piezoelectric micro-nozzle of the micro-inkjet printing apparatus according to the present invention;
description of reference numerals:
1. a pneumatic controller; an XY displacement stage; 3. a camera; 4. piezoelectric micro-spray head and closed container; 5, an XY displacement table data acquisition and control system and an environment control and measurement unit; 6. a two-dimensional or three-dimensional table; 7. a piezoelectric micro-nozzle control system; a waste liquid tank; 9. a strobe light; 10. a closed container; 11. piezoelectric micro-nozzle
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to specific embodiments and the accompanying drawings.
The invention provides a device for locally modifying a biochemical molecular layer for a micro sensor, which realizes local modification of the biochemical molecular layer by adopting micro ink jet printing equipment with a piezoelectric micro spray head 4, an XY displacement table 2 and a two-dimensional or three-dimensional workbench 6.
As shown in fig. 1, fig. 1 is a schematic structural diagram of a micro-inkjet printing apparatus for a device for locally modifying a biochemical molecular layer for a micro-sensing device according to an embodiment of the present invention. It mainly comprises: the piezoelectric micro-nozzle 4 is used for printing modified biochemical molecules; the air pressure controller 1 is used for controlling and sealing the air pressure of the container; the closed container 4 is used for containing a solution containing biochemical molecules to be printed and is respectively connected with the air pressure controller and the piezoelectric micro-sprayer through the guide pipe to realize the liquid level control of the piezoelectric sprayer; the piezoelectric micro-spray head control system 7 is used for adjusting and controlling the size, the number and the state of printing liquid drops; a two-dimensional or three-dimensional table 6 for placing a device to be printed; the XY displacement table 2 is placed on a high-precision displacement XY displacement table, and can move in a horizontal plane along with the XY displacement table; two cameras 3 for three-dimensionally observing the positions of the micro-nozzles and the devices and the printing condition of liquid drops from the X direction and the Y direction respectively; the XY displacement table data acquisition and control system can accurately control the movement displacement of the displacement table in each XY direction and set the movement step length through a software program, and the environment control and measurement unit is used for controlling and detecting proper environment conditions required in the biochemical molecule printing process, wherein the environment conditions comprise temperature and humidity.
In order to ensure the high precision of the micro-ink-jet printing device, the micro-ink-jet printing system of the local modification biochemical molecular layer device for the micro-sensor device adopts a device to be printed placing device as shown in fig. 2, the surface of the device to be printed is placed upwards on a two-dimensional or three-dimensional workbench 6, the position to be printed is accurately moved to the position right opposite to a nozzle by controlling an XY displacement table 2, a camera 3 and the nozzle 4 are finely adjusted to obtain a clear image, and the size, the number and the state of liquid drops are adjusted by setting voltage signals and pulse signal parameters through a piezoelectric micro-nozzle control system 7, so that the printing modification process is completed.
As shown in fig. 3, fig. 3 is a schematic structural diagram of a closed container and a piezoelectric micro-nozzle of a micro-inkjet printing device, wherein the closed container and the micro-nozzle are fixed in a clamping groove, the clamping groove is fixed on a same inverted U-shaped bracket through a connecting piece and a camera, and the micro-nozzle is perpendicular to a horizontal plane. And the connecting piece is fixed on a displacement table through screws and can move up and down and left and right. The biochemical molecular liquid to be printed is filled into a closed container, the pressure in the closed container is far higher than the external pressure through an air pressure controller, the biochemical molecules flow through the micro-spray head through a guide pipe to form continuous flow, an air pressure control system is closed to enable the pressure in the closed container to be the same as the external pressure, and the liquid level at the tail end of the micro-spray head is static and finely adjusted until the liquid level is parallel to the tail end of the micro-spray head. The position of the spray nozzle is adjusted until the observation camera takes the phase, the spray nozzle can be observed, and then the distance between the camera and the spray nozzle is adjusted to adjust the focal length to obtain a clear image.
Local modification is carried out by using a micro ink-jet printing method, a modification area and a dosage are accurately controlled, a printing area is accurately positioned, and high-precision local modification of a device is realized.
The above-mentioned embodiments, to the purpose, technical solution and beneficial effects of the present invention have been described in detail, it should be understood that the above-mentioned is only the embodiments of the present invention, and is not intended to limit the present invention, and any modifications, equivalent substitutions, improvements, etc. made within the spirit, concept and principle of the present invention should be included in the scope of the present invention.
Claims (8)
1. A device for locally modifying a biochemical molecular layer for a micro-sensing device, which is suitable for devices of various specifications and for large-scale local modification schemes, comprises:
the piezoelectric micro-nozzle is used for printing the modified biochemical molecules;
the air pressure controller is used for controlling and adjusting the air pressure of the closed container;
the closed container is used for containing a solution containing biochemical molecules to be printed and is respectively connected with the air pressure controller and the piezoelectric micro-sprayer through the guide pipe to realize the liquid level control of the piezoelectric sprayer;
the piezoelectric micro-nozzle control system is used for adjusting and controlling the size, the number and the state of printing liquid drops;
a two-dimensional or three-dimensional table for placing the printed device and controlling the rotation of the device at the home position;
the two-dimensional or three-dimensional workbench is placed on the XY displacement platform with high precision displacement and can move in a horizontal plane along with the XY displacement platform;
an XY displacement table data acquisition and control system, which can accurately control the XY direction movement displacement of the displacement table through a software program;
the two cameras are used for respectively observing the positions of the micro-nozzles and the devices in X and Y directions and the printing condition of liquid drops in a three-dimensional mode;
and the environment control and measurement unit is used for controlling and detecting the appropriate environment conditions required in the biochemical molecule printing process, wherein the environment conditions comprise temperature and humidity.
2. The apparatus according to claim 1, wherein the two cameras are fixed on an inverted U-shaped bracket through L-shaped stands, one camera is used for observing the X direction, the other camera is used for observing the Y direction, a light source is respectively arranged in the direction opposite to the two cameras during observation to facilitate observation, the two cameras can be rotated in a direction perpendicular to the horizontal plane through the rotating structure, and the cameras can be adjusted up and down and left and right through the displacement table.
3. The device according to claim 1, wherein the closed container and the micro-nozzle are fixed in a slot, the slot is fixed on a reversed U-shaped bracket through a connector, the micro-nozzle is perpendicular to the horizontal plane, the connector is fixed on a displacement table through screws, the connector can move up and down and left and right, the X-direction camera and the micro-nozzle are in the same plane, and the Y-direction camera is adjusted to be in the same plane as the micro-nozzle, thereby being more beneficial to observing the printing state during printing, the end of the nozzle can be in the observation range of the camera by adjusting the micro-nozzle up and down, and the focusing distance of the camera can be adjusted by adjusting the micro-nozzle left and right.
4. The apparatus of claim 1, wherein the printed device is placed on a two-dimensional or three-dimensional table, and the surface to be printed is opposite to the micro-nozzle.
5. The device for locally modifying a biochemical molecule layer for a micro sensor device according to claim 1, wherein the two-dimensional or three-dimensional worktable is fixed on the XY displacement table through screws, and the center of the worktable is opposite to the micro nozzle, the rotatable platform of the three-dimensional worktable is made of transparent glass, the brightness around the device can be improved by the transparent glass, which is more beneficial for the observation of a camera and high-definition image taking, or a strobe lamp is installed below the two-dimensional worktable, and the strobe lamp, the micro nozzle and the high-definition camera are in a line when adjusting liquid drops or printing, so that the state of the liquid drops can be conveniently observed, the surface printing condition of the printed device can be observed, and high-definition image taking is facilitated.
6. The apparatus according to claim 1, wherein the two-dimensional or three-dimensional stage has a waste liquid tank, and a culture dish is disposed below the waste liquid tank for containing waste liquid generated by the conditioning liquid drop so as to prevent contamination of other areas of the apparatus.
7. The apparatus according to claim 1, wherein the air pressure controller is configured to apply positive and negative air pressures.
8. The apparatus of claim 1, wherein the closed container has a sealing cap which can be opened and closed by rotation, the sealing cap is opened by rotation when a liquid containing biochemical molecules is printed, and the sealing cap is closed by rotation after the liquid is printed, the sealing cap has two conduits for communicating the closed container with the micro-nozzle and the air pressure controller, wherein the conduit connected to the air pressure controller extends only to the mouth of the sealing cap, and the conduit connected to the micro-ink-jet printing system extends to the bottom of the closed container.
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| CN109822882A (en) * | 2019-03-20 | 2019-05-31 | 天津工业大学 | A kind of part modification biochemical molecular layer method for micro sensor devices |
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