CN115060849A - Modularized micro-fluidic chip - Google Patents

Abstract

The present disclosure relates to a modular microfluidic chip. The modularized micro-fluidic chip comprises a biological sample processing reaction chip and a silicon substrate biosensor module. The micro-fluidic chip is suitable for integration of various silicon substrate biosensors, the whole chip is guaranteed to be sealed and stored while sample pretreatment is completed, the samples are accurately transported to the detection unit respectively after being treated, reliable and rapid integration of the plastic injection molding micro-fluidic chip and the electrical sensing device can be realized, the method is simple and rapid, high-throughput detection can be compatible, and a solution is provided for miniaturization and light weight of on-site rapid pathogen detection equipment.

Description

Modularized micro-fluidic chip

Technical Field

The disclosure relates to the field of microfluidic chips, in particular to a modular microfluidic chip.

Background

The demand for rapid detection of pathogenic microorganisms is increasing, higher requirements are put on the sensitivity, portability, integration and automation of detection equipment and detection methods, the traditional chemiluminescence (such as a fluorescent quantitative PCR process) based on a probe labeling mode is time-consuming and labor-consuming in the labeling process, a large amount of labor cost and time cost are required, and the activity of biomolecules (such as antibodies and enzymes) is lost in the labeling process to influence the analysis effect. Therefore, the label-free biosensor is bound to become a mainstream device for future biological detection, such as a SiNW-FET biosensor, and has the advantages of rapidness, small size, high detection sensitivity, strong specificity and the like. However, most label-free biosensors only achieve stable and sensitive detection on a substance to be detected in a relatively pure processed state, and therefore, a sample pretreatment process under a professional biological laboratory condition needs to be relied on, so that the detection process is complex, the timeliness is poor, the professional requirement is strong, flexible deployment is difficult, the application scene is very limited, and the advantages of small size, high sensitivity and rapid response of the label-free biosensors cannot be exerted.

The micro-fluidic chip is a rapid analysis platform which can integrate basic operations such as sample preparation, reaction, separation, detection and the like involved in the biological, chemical and medical analysis processes. Based on the characteristics of small volume, low reagent consumption, high integration and the like, the micro-fluidic chip has great application potential in the fields of biology, chemistry, medical treatment and the like, and has gradually developed into a research field of high cross fusion of biochemistry, hydrodynamics, microelectronics, materials, machinery and the like. At present, most of detection methods of microfluidic chips are based on traditional chemiluminescent detection in a probe labeling mode, and interpretation of results is realized through changes of fluorescence intensity or color turbidity in a detection chamber. The equipment needs to introduce a precise optical detection system, so that the cost, the volume and the weight of the equipment are greatly improved.

Accordingly, there is a need for one or more methods to address the above-mentioned problems.

It is to be noted that the information disclosed in the above background section is only for enhancement of understanding of the background of the present disclosure, and thus may include information that does not constitute prior art known to those of ordinary skill in the art.

Disclosure of Invention

It is an object of the present disclosure to provide a modular microfluidic chip, thereby overcoming, at least to some extent, one or more of the problems due to the limitations and disadvantages of the related art.

According to an aspect of the present disclosure, there is provided a modular microfluidic chip comprising a biological sample processing reaction chip, a silicon substrate biosensor module, wherein:

the biological sample treatment reaction chip comprises a biological sample treatment reaction upper layer chip and a biological sample treatment reaction lower layer chip, and is used for receiving a sample to be detected, carrying out treatment based on biological reaction on the sample to be detected, and transferring and pushing the treated sample to be detected to the silicon substrate biosensor module;

the silicon substrate biosensor module comprises a detection sensing unit and a PCB substrate, wherein the detection sensing unit is used for receiving and detecting the processed sample to be detected and generating a detection result electric signal.

In an exemplary embodiment of the present disclosure, the biological sample processing reaction upper chip of the microfluidic chip further includes a sample inlet to be detected, an air pressure balancing port, a reaction detection interface unit, a liquid channel, and a sample processing chamber, wherein:

the structure of the sample inlet to be detected is in a standard luer structure form, and the sample inlet to be detected is used for receiving the sample to be detected;

the sample processing chamber is connected with the sample inlet to be detected through a liquid channel and is used for processing the sample to be detected based on biological reaction;

the reaction detection interface unit is connected with the sample processing chamber through a liquid channel and is used for receiving the processed sample to be detected;

the air pressure balancing port is connected with the reaction detection interface unit through a liquid channel and is used for keeping the internal sealing and air pressure balance of the biological sample processing reaction upper chip when receiving the sample to be detected or transmitting the processed sample to be detected.

In an exemplary embodiment of the present disclosure, the reaction detection interface unit of the microfluidic chip further includes a transfer chamber, a detection transfer interface:

the transfer chamber is used for receiving the processed sample to be detected and transmitting the processed sample to be detected to the detection adapter port;

the height ratio of the detection adapter port to the transfer chamber is 10:1-1:1, and the detection adapter port is used for receiving the processed sample to be detected transmitted by the transfer chamber and transmitting the processed sample to be detected to the biological sample processing reaction lower chip.

In an exemplary embodiment of the present disclosure, the biological sample processing reaction lower layer chip of the microfluidic chip further includes:

and the detection chamber upper channel is used for receiving the processed sample to be detected transmitted by the detection adapter.

In an exemplary embodiment of the present disclosure, in the biological sample treatment reaction chip of the microfluidic chip, the biological sample treatment reaction upper chip and the biological sample treatment reaction lower chip are combined by one or more of laser bonding, ultrasonic bonding, thermocompression bonding, and adhesive bonding.

In an exemplary embodiment of the present disclosure, the detection sensing unit of the microfluidic chip further includes:

the detection chamber is used for receiving the processed sample to be detected, which is transmitted by the channel on the detection chamber, and the detection chamber is of a sealing structure;

the silicon substrate biological sensing device is used for detecting the processed sample to be detected, generating a corresponding detection result electric signal and sending the detection result electric signal to an electrode;

and the electrode is used for receiving a detection result electric signal sent by the silicon substrate biosensor and is led out to the outer side of the PCB substrate through the extension pin.

In an exemplary embodiment of the present disclosure, the microfluidic chip further includes:

the biological sample processing reaction chip further comprises a reaction chip lower-layer buckle structure, the silicon substrate biosensor module comprises a sensing module buckle, the reaction chip lower-layer buckle structure and the sensing module buckle are in buckle combination, and the biological sample processing reaction chip is combined with the silicon substrate biosensor module.

In an exemplary embodiment of the present disclosure, the microfluidic chip further includes:

the biological sample processing reaction chip further comprises a sealing rubber pad, the silicon substrate biosensor module comprises a waterproof isolation structure, and the sealing rubber pad is connected with the waterproof isolation structure through the lower-layer buckle structure of the reaction chip and the buckle combination positive pressure of the sensing module to realize the sealing combination of the biological sample processing reaction chip and the silicon substrate biosensor module.

In an exemplary embodiment of the present disclosure, a modular microfluidic chip includes a biological sample processing reaction chip, a silicon substrate biosensor module. The micro-fluidic chip is suitable for integration of various silicon substrate biosensors, the whole chip is guaranteed to be sealed and stored while sample pretreatment is completed, the samples are accurately transported to the detection unit respectively after being treated, reliable and rapid integration of the plastic injection molding micro-fluidic chip and the electrical sensing device can be realized, the method is simple and rapid, high-throughput detection can be compatible, and a solution is provided for miniaturization and light weight of on-site rapid pathogen detection equipment.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosure.

Drawings

The above and other features and advantages of the present disclosure will become more apparent by describing in detail exemplary embodiments thereof with reference to the attached drawings.

Fig. 1 shows a schematic overall structure of a modular microfluidic chip according to an exemplary embodiment of the present disclosure;

fig. 2 shows a top view of a biological sample processing reaction chip of a modular microfluidic chip according to an exemplary embodiment of the present disclosure;

fig. 3 shows a top-bottom cross-sectional view of a biological sample processing reaction chip of a modular microfluidic chip according to an exemplary embodiment of the present disclosure;

FIG. 4 illustrates a top view of a silicon substrate biosensor module of a modular microfluidic chip according to an exemplary embodiment of the present disclosure;

figure 5 illustrates a silicon substrate biosensor module cross-sectional view of a modular microfluidic chip according to an exemplary embodiment of the present disclosure,

the biological sample processing reaction upper chip 1 comprises a sample inlet 11, an air pressure balancing port 12, a reaction detection interface unit 13, a detection switching port 131, a transfer chamber 132, a liquid channel 14 and a sample processing chamber 15; the biological sample processing reaction lower chip 2 comprises a reaction chip lower layer buckling structure 21, a sealing rubber pad 22 and a detection chamber upper channel 23; the silicon substrate biosensor module 3 comprises a detection sensing unit 31, a silicon substrate biosensor device 311, electrodes 312, a detection chamber 313, a row-inserting type pin 314, a PCB substrate 32, a waterproof isolation structure 33 and a sensing module buckle 34.

Detailed Description

Example embodiments will now be described more fully with reference to the accompanying drawings. Example embodiments may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of example embodiments to those skilled in the art. The same reference numerals denote the same or similar parts in the drawings, and thus, a repetitive description thereof will be omitted.

Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided to give a thorough understanding of embodiments of the disclosure. One skilled in the relevant art will recognize, however, that the embodiments of the disclosure can be practiced without one or more of the specific details, or with other methods, components, materials, devices, steps, and the like. In other instances, well-known structures, methods, devices, implementations, materials, or operations are not shown or described in detail to avoid obscuring aspects of the disclosure.

The block diagrams shown in the figures are functional entities only and do not necessarily correspond to physically separate entities. That is, these functional entities may be implemented in the form of software, or in one or more software-hardened modules, or in different networks and/or processor devices and/or microcontroller devices.

In the present example embodiment, there is first provided a modular microfluidic chip; referring to fig. 1, the modular microfluidic chip comprises a biological sample processing reaction chip, a silicon substrate biosensor module 3, wherein:

the biological sample treatment reaction chip comprises a biological sample treatment reaction upper layer chip 1 and a biological sample treatment reaction lower layer chip 2, and is used for receiving a sample to be detected, carrying out biological reaction-based treatment on the sample to be detected, and transferring and pushing the treated sample to be detected to a silicon substrate biosensor module 3;

the silicon substrate biosensor module 3 comprises a detection sensing unit 31 and a PCB substrate 32, wherein the detection sensing unit 31 is used for receiving and detecting the processed sample to be detected and generating a detection result electric signal.

A modular microfluidic chip in an exemplary embodiment of the present disclosure, wherein the modular microfluidic chip includes a biological sample processing reaction chip, a silicon substrate biosensor module 3. The micro-fluidic chip is suitable for integration of various silicon substrate biosensors, the whole chip is guaranteed to be sealed and stored while sample pretreatment is completed, the samples are accurately transported to the detection unit respectively after being treated, reliable and rapid integration of the plastic injection molding micro-fluidic chip and the electrical sensing device can be realized, the method is simple and rapid, high-throughput detection can be compatible, and a solution is provided for miniaturization and light weight of on-site rapid pathogen detection equipment.

Next, a modular microfluidic chip in the present exemplary embodiment will be further described.

The first embodiment is as follows:

the microfluidic chip biological sample treatment reaction chip and the silicon substrate biosensor module 3 are characterized in that:

the biological sample treatment reaction chip comprises a biological sample treatment reaction upper layer chip 1 and a biological sample treatment reaction lower layer chip 2, and is used for receiving a sample to be detected, carrying out biological reaction-based treatment on the sample to be detected, and transferring and pushing the treated sample to be detected to a silicon substrate biosensor module 3.

In the embodiment of the present example, as shown in fig. 1 and 2, the biological sample processing reaction upper layer chip 1 of the microfluidic chip further includes a sample inlet 11 to be detected, an air pressure balancing port 12, a reaction detection interface unit 13, a liquid channel 14, and a sample processing chamber 15, wherein:

the structure of the sample inlet 11 to be detected is in a standard luer structure form, and is used for receiving the sample to be detected;

the sample processing chamber 15 is connected with the sample inlet 11 to be detected through a liquid channel 14, and is used for processing the sample to be detected based on biological reaction;

the reaction detection interface unit 13 is connected to the sample processing chamber 15 through a liquid channel 14, and is configured to receive the processed sample to be detected;

the air pressure balancing port 12 is connected with the reaction detection interface unit 13 through a liquid channel 14, and is used for keeping the internal sealing and air pressure balance of the biological sample processing reaction upper chip 1 when receiving the sample to be detected or transmitting the processed sample to be detected.

In the embodiment of the present example, the reaction detection interface unit 13 of the microfluidic chip further includes a transfer chamber 132, a detection transfer interface 131:

the transfer chamber 132 is configured to receive the processed sample to be detected, and transmit the processed sample to be detected to the detection adapter 131;

the height ratio of the detection adapter 131 to the transfer chamber 132 is 10:1-1:1, and the detection adapter is used for receiving the processed sample to be detected transmitted by the transfer chamber 132 and transmitting the processed sample to be detected to the biological sample processing reaction lower chip 2.

In the embodiment of the present example, the first part is a biological sample processing reaction chip, and is composed of a biological sample processing reaction chip upper layer and a biological sample processing reaction chip lower layer, respectively; the second part is a silicon substrate biosensor module 3, the biosensor outputs electrical signals and is integrated on a PCB. The upper layer of the biological sample processing reaction chip comprises a sample inlet 11 and an air pressure balancing port 12, and the air pressure balancing port 12 has a water-blocking and air-permeable function; the sample inlet 11 and the air pressure balance port 12 are combined and connected by a liquid channel 14, a sample processing chamber 15 and a reaction detection interface unit 13, and can be freely combined according to the requirements of different biological reaction steps; the sample inlet 11 structure adopts a standard luer interface form, and improves the property of a universal interface. The reaction detection interface unit 13 comprises a transfer chamber 1321 and a detection adapter 131, wherein the height of the transfer chamber 132 is higher than that of the detection adapter 131, and the ratio is 10:1 to 1: 1.

In the present exemplary embodiment, the biological sample processing reaction lower chip 2 of the microfluidic chip further includes:

a channel 23 on the detection chamber 313, wherein the channel 23 on the detection chamber 313 is used for receiving the processed sample to be detected transmitted by the detection adapter 131.

In the present exemplary embodiment, in the biological sample processing reaction chip of the microfluidic chip, the biological sample processing reaction upper chip 1 and the biological sample processing reaction lower chip 2 are bonded by one or more of laser bonding, ultrasonic bonding, thermocompression bonding, and adhesive bonding.

In the embodiment of the present example, the lower layer of the reaction chip for processing biological samples includes the channel 23 on the detection chamber 313, the sealing rubber pad 22 and the snap structure 21 on the lower layer of the reaction chip for processing biological samples.

The silicon substrate biosensor module 3 comprises a detection sensing unit 31 and a PCB substrate 32, wherein the detection sensing unit 31 is used for receiving and detecting the processed sample to be detected and generating a detection result electric signal.

In the embodiment of the present example, the detection sensing unit 31 of the microfluidic chip further includes:

the detection chamber 313 is used for receiving the processed sample to be detected, which is transmitted by the channel 23 on the detection chamber 313, and the detection chamber 313 is in a sealing structure;

the silicon substrate biological sensing device 311 is used for detecting the processed sample to be detected, generating a corresponding detection result electric signal and sending the detection result electric signal to the electrode 312;

and the electrode 312 is used for receiving a detection result electric signal sent by the silicon substrate biosensor 311 and leading out to the outer side of the PCB substrate 32 through a pin 314.

In an embodiment of the present example, the microfluidic chip further comprises:

the biological sample processing reaction chip further comprises a reaction chip lower-layer buckle structure 21, the silicon substrate biosensor module 3 comprises a sensing module buckle 34, the reaction chip lower-layer buckle structure 21 and the sensing module buckle 34 are in buckle combination, and the biological sample processing reaction chip is combined with the silicon substrate biosensor module 3.

In an embodiment of the present example, the microfluidic chip further comprises:

biological sample handles reaction chip still includes sealed cushion 22, silicon substrate biosensor module 3 includes waterproof isolating structure 33, sealed cushion 22 with waterproof isolating structure 33 passes through reaction chip lower floor buckle structure 21 with sensing module's buckle combination malleation is connected, realizes biological sample handles reaction chip with silicon substrate biosensor module 3's sealed combination.

In the embodiment of the present example, as shown in fig. 3 and 4, the silicon substrate biosensor module 3 includes a PCB substrate 32, a detection sensing unit 31, a waterproof isolation structure 33 and a sensing module buckle 34 matched with the lower layer buckle structure 21 of the biological sample processing reaction chip; the detection sensing unit 31 comprises a silicon substrate biosensor 311, an electrode 312, a detection chamber 313 and a patch type pin 314, wherein the sensor and the electrode 312 are electrically connected in a metal wire bonding mode and are led out to the patch type pin 314 on the back surface of the sensor through a PCB (printed circuit board) through hole, an electrical excitation signal and a device output electrical signal are connected with the outside through the pin, the detection chamber 313 is formed by a waterproof isolation structure 33 and the silicon substrate biosensor 311 together, and it is required to ensure that a sensitive interface of the silicon substrate biosensor 311 is exposed in the chamber.

The biological sample treatment reaction chip can be made of hard polymer thermoplastic materials such as PP, PC, PET, PTFE, COC and the like, and is processed by methods such as injection molding and the like. The upper layer of the biological sample treatment reaction chip and the lower layer of the biological sample treatment reaction chip can be realized by laser bonding, ultrasonic bonding, hot-press bonding, glue bonding and the like; the sealing rubber pad 22 can be made of liquid silica gel, TPE, TPU, PDMS and the like, and the integration mode of the sealing rubber pad and the lower layer of the biological sample processing reaction chip can be integrated by encapsulation molding, double-color injection molding or adhesive bonding and the like. The silicon substrate biosensor module 3 may be implemented by a conventional PCB fabrication bonding process.

The biological sample treatment reaction chip and the silicon substrate biosensor module 3 are physically connected through a buckle structure, and the sealing rubber pad 22 is deformed and extruded through interference fit to seal a liquid cavity.

Example two:

in the embodiment of the present invention, taking rapid detection of a virus sample as an example, the module of the present invention mainly involves the following steps:

putting the collected sample into a special syringe filled with sample processing liquid, carrying out sample cracking, connecting the special syringe with a sample inlet 11 luer after the processing is finished, pushing the sample into a chip, stopping the flow of liquid at the downstream of a cavity due to the fact that the sample amount is the same as the volume of the cavity, pre-embedding a corresponding biological reaction reagent in a sample processing cavity 15, and carrying out a pre-amplification process at a preset temperature.

After the pre-amplification process is completed. The sample is continuously pushed into the transfer chamber 132 by the special syringe, and because the detection chamber 313 is a closed chamber, the sample stops at the air pressure balance port 12 after filling all the transfer chambers 132 according to the flow resistance and air pressure action rule, and does not enter the chamber in the detection chamber 313.

After the liquid stops at the air pressure balancing port 12, the liquid rotates along the radial direction (the transfer chamber 132 is towards the detection adapter 131) through the rotating device of the device, and the centrifugal force will make the sample in the transfer chamber 132 finally enter the detection chamber 313 through the detection adapter 131 to contact with the sensing unit of the biosensor device. The centrifugal device can be manually swung without rotating the centrifugal device, and the swinging direction is the direction from the transfer chamber 132 to the detection adapter 131.

It should be noted that although in the above detailed description several modules or units of a modular microfluidic chip are mentioned, this division is not mandatory. Indeed, the features and functionality of two or more modules or units described above may be embodied in one module or unit, according to embodiments of the present disclosure. Conversely, the features and functions of one module or unit described above may be further divided into embodiments by a plurality of modules or units.

Furthermore, the above-described drawings are only schematic illustrations of processes included in an apparatus according to an exemplary embodiment of the present invention, and are not intended to be limiting. It will be readily understood that the processes shown in the above figures are not intended to indicate or limit the chronological order of the processes. In addition, it is also readily understood that these processes may be performed synchronously or asynchronously, e.g., in multiple modules.

Other embodiments of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. This application is intended to cover any variations, uses, or adaptations of the disclosure following, in general, the principles of the disclosure and including such departures from the present disclosure as come within known or customary practice within the art to which the disclosure pertains. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the disclosure being indicated by the following claims.

It will be understood that the present disclosure is not limited to the precise arrangements that have been described above and shown in the drawings, and that various modifications and changes may be made without departing from the scope thereof. The scope of the present disclosure is to be limited only by the terms of the appended claims.

Claims (8)

1. A modular microfluidic chip, comprising a biological sample processing reaction chip, a silicon substrate biosensor module, wherein:

the biological sample treatment reaction chip comprises a biological sample treatment reaction upper layer chip and a biological sample treatment reaction lower layer chip, and is used for receiving a sample to be detected, carrying out treatment based on biological reaction on the sample to be detected, and transferring and pushing the treated sample to be detected to the silicon substrate biosensor module;

the silicon substrate biosensor module comprises a detection sensing unit and a PCB substrate, wherein the detection sensing unit is used for receiving and detecting the processed sample to be detected and generating a detection result electric signal.

2. The microfluidic chip according to claim 1, wherein the upper chip for biological sample processing reaction of the microfluidic chip further comprises a sample inlet to be detected, an air pressure balancing port, a reaction detection interface unit, a liquid channel, and a sample processing chamber, wherein:

the structure of the sample inlet to be detected is in a standard luer structure form, and the sample inlet to be detected is used for receiving the sample to be detected;

the sample processing chamber is connected with the sample inlet to be detected through a liquid channel and is used for processing the sample to be detected based on biological reaction;

the reaction detection interface unit is connected with the sample processing chamber through a liquid channel and is used for receiving the processed sample to be detected;

the air pressure balancing port is connected with the reaction detection interface unit through a liquid channel and is used for keeping the internal sealing and air pressure balance of the biological sample processing reaction upper chip when receiving the sample to be detected or transmitting the processed sample to be detected.

3. The microfluidic chip according to claim 2, wherein the reaction detection interface unit of the microfluidic chip further comprises a transfer chamber, a detection transfer interface:

the transfer chamber is used for receiving the processed sample to be detected and transmitting the processed sample to be detected to the detection adapter port;

the height ratio of the detection adapter port to the transfer chamber is 10:1-1:1, and the detection adapter port is used for receiving the processed sample to be detected transmitted by the transfer chamber and transmitting the processed sample to be detected to the biological sample processing reaction lower chip.

4. The microfluidic chip according to claim 3, wherein the lower chip for biological sample processing reaction of the microfluidic chip further comprises:

and the detection chamber upper channel is used for receiving the processed sample to be detected transmitted by the detection adapter.

5. The microfluidic chip according to claim 1, wherein the upper chip of the biological sample processing reaction layer and the lower chip of the biological sample processing reaction layer of the microfluidic chip are bonded by one or more of laser bonding, ultrasonic bonding, thermocompression bonding, and adhesive bonding.

6. The microfluidic chip according to claim 1, wherein the detection sensing unit of the microfluidic chip further comprises:

the detection chamber is used for receiving the processed sample to be detected, which is transmitted by the channel on the detection chamber, and the detection chamber is of a sealing structure;

the silicon substrate biological sensing device is used for detecting the processed sample to be detected, generating a corresponding detection result electric signal and sending the detection result electric signal to an electrode;

and the electrode is used for receiving a detection result electric signal sent by the silicon substrate biosensor and leading out to the outer side of the PCB substrate through the extension pin.

7. The microfluidic chip according to claim 1, further comprising:

the biological sample processing reaction chip further comprises a reaction chip lower-layer buckle structure, the silicon substrate biosensor module comprises a sensing module buckle, the reaction chip lower-layer buckle structure and the sensing module buckle are in buckle combination, and the biological sample processing reaction chip is combined with the silicon substrate biosensor module.

8. The microfluidic chip of claim 7, wherein the microfluidic chip further comprises:

the biological sample processing reaction chip further comprises a sealing rubber pad, the silicon substrate biosensor module comprises a waterproof isolation structure, and the sealing rubber pad is connected with the waterproof isolation structure through the lower-layer buckle structure of the reaction chip and the buckle combination positive pressure of the sensing module to realize the sealing combination of the biological sample processing reaction chip and the silicon substrate biosensor module.

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