KR101953012B1 - Chamber chip, blood testing device including the chamber chip and method of manufacturing the blood testing device - Google Patents

Abstract

A blood testing apparatus according to an embodiment includes: a piezoelectric substrate; A surface acoustic wave generating unit disposed on the piezoelectric substrate to generate a surface acoustic wave; And a chamber element disposed on the piezoelectric substrate, the chamber element being spaced apart from the surface acoustic wave generating part and transmitting surface acoustic waves generated from the surface acoustic wave generating part, wherein the chamber element comprises: a chamber member for holding a blood sample therein; And an internal flow can be generated in the blood sample in the chamber member by surface acoustic waves generated in the surface acoustic wave generating part.

Description

TECHNICAL FIELD [0001] The present invention relates to a chamber device, a blood testing device including the chamber device, and a method of manufacturing the blood testing device. [0002]

The present invention relates to a chamber device, a blood testing device including the chamber device, and a method of manufacturing the blood testing device, and more particularly, to a method of manufacturing a blood testing device capable of inducing microflows in a blood sample using surface acoustic waves A chamber device including the chamber device, a blood testing device including the chamber device, and a method of manufacturing the blood testing device.

Platelet function tests are often used to test bleeding disorders due to congenital or acquired platelet dysfunction and to test resistance to antiplatelet drugs. It is also widely used as a screening test to determine the preoperative bleeding tendency.

In order to measure the function of platelets, an activator to activate platelets is required, which can be divided into biochemical stimulation and biological stimulation.

Biochemical activators include thrombin in the blood, adenosine diphosphate (ADP), von Willebrand factor (vWF), and the like.

On the other hand, there is a method of applying a shearing force in the blood flow as a biological stimulus. The platelets, which are affected by the high rate of decay, are activated and adhere to the vascular endothelium and aggregate.

Recently, Platelet Function Analyzer (eg, PFA-200) and VerifyNow have been developed as a technique for measuring platelet function.

In the case of VerifyNow, blood is injected into a sample chamber containing bead coated with a biochemical activator, such as figrinoge, and mixing of the sample is performed by the movement of a mixing ball located in the chamber. This activates the platelets in the blood and binds to the fibrinogen to promote platelet aggregation. Then, the light transmittance is measured through an optical sensor to evaluate the function of platelets. However, this method, like existing turbidity measurement methods, requires an optical system for measurement and it may be difficult to measure fine changes in the sample as turbidity.

PFA-200, on the other hand, activates platelets in the blood with a high rate of decay in the long capillary and then coalesces platelets with adenosine diphosphate or epinephrine-coated orifices coadministered with collagen Measurement method is used. However, this approach is dependent on the function of the von Willebrand factor outside the platelets in the blood, and a large amount of blood may be required.

An object of the present invention is to provide a chamber device capable of effectively evaluating the degree of activation of platelets in a blood sample by inducing microfluidic flow in a blood sample using surface acoustic waves and controlling the intensity thereof, And a method for manufacturing the blood test apparatus.

The object of the present invention is to provide a chamber device capable of controlling the degree of activation of platelets according to the magnitude of the AC voltage applied to the input electrode and the time of applying the AC voltage and controlling the flow direction according to the frequency band, A blood test apparatus including a chamber element, and a method of manufacturing the blood test apparatus.

An object of the present invention is to provide a chamber device capable of uniformly activating platelets present in a blood sample and more precisely detecting the function and activity of platelets based on the minute difference in electric resistance, And a method for manufacturing the blood test apparatus.

An object of the present invention is to provide a chamber device capable of reversibly bonding on a piezoelectric substrate and capable of being joined or separated from an output electrode disposed on a piezoelectric substrate so that the chamber device can be discarded after inspection and replaced with a new product, And a method for manufacturing the blood test apparatus.

An object according to an embodiment is to provide a chamber device capable of holding a blood sample in a dome or a hemispherical channel so that a high shear force or a high surface acoustic wave (or acoustic power) can be effectively transmitted to a blood sample, , A blood test apparatus including the chamber element, and a method of manufacturing the blood test apparatus.

An object of the present invention is to provide a chamber device which can be miniaturized as a whole and which can easily control the flow of a blood sample through electrical control, a blood testing device including the chamber device, and a method of manufacturing the blood testing device will be.

An object of an embodiment is to provide a chamber device capable of performing various tests on a blood sample as well as an evaluation of the function and activity of platelets, a blood test apparatus including the chamber device, and a method of manufacturing the blood test apparatus .

According to one aspect of the present invention, there is provided a blood testing apparatus including: a piezoelectric substrate; A surface acoustic wave generating unit disposed on the piezoelectric substrate to generate a surface acoustic wave; And a chamber element disposed on the piezoelectric substrate, the chamber element being spaced apart from the surface acoustic wave generating part and transmitting surface acoustic waves generated from the surface acoustic wave generating part, wherein the chamber element comprises: a chamber member for holding a blood sample therein; And an internal flow can be generated in the blood sample in the chamber member by surface acoustic waves generated in the surface acoustic wave generating part.

According to one aspect, a dome or hemispherical channel is formed in the chamber member, and the blood sample can be held in the dome or hemispherical channel.

According to one aspect, the chamber element includes: a base substrate disposed at a lower portion of the chamber member; And a detection electrode disposed on the base substrate and detecting electrical characteristics of an object to be detected in the blood sample, wherein the detection electrode is disposed under the dome or hemispherical channel.

According to one aspect of the present invention, the base substrate is reversibly bonded by the coupling liquid on the piezoelectric substrate, and surface acoustic waves generated in the surface acoustic wave generating portion are bonded to the blood sample held in the chamber member through the coupling liquid Lt; / RTI >

According to one aspect of the present invention, the piezoelectric substrate is provided with an output electrode which is electrically connected to the detection member and transmits the electrical characteristics of the blood sample detected by the detection electrode, and the end of the detection electrode and the output electrode are connected to each other May be removable.

According to one aspect of the present invention, the detection member is provided with an adsorbent material to which the detection object in the blood sample is adsorbed, and the detection target in the blood sample circulates in the chamber member by the surface acoustic wave generated in the surface acoustic wave generation unit And adsorbed on the adsorbent material.

According to one aspect of the present invention, the surface acoustic wave generating unit includes: an input electrode to which electrical energy is applied; And a transducer electrically connected to the input electrode and converting the applied electric energy into a surface acoustic wave, wherein the input electrode and the transducer are patterned on the piezoelectric substrate, and the electrical energy applied to the electrode The flow characteristics of the blood sample can be controlled by control.

According to an aspect of the present invention, there is provided a chamber device comprising: a base substrate; And a chamber member disposed on the base substrate and into which a sample is injected, wherein the chamber member has a dome or hemispherical shape, and a channel in which the sample is held therein, wherein when the external force is applied, A gradient of the hydrodynamic force may be generated in the sample due to the height difference of the sample, and an internal flow may be generated in the sample.

According to one aspect of the present invention, the chamber member includes: an injection section communicating with the channel to inject the sample; And a discharge compartment communicating with the channel and discharging the sample, the channel being disposed between the injection compartment and the discharge compartment.

According to one aspect of the present invention, there is provided an image pickup apparatus comprising: an adsorption member disposed on the base substrate to adsorb an object to be detected in the sample; And a detection member disposed between the base substrate and the adsorption member, wherein the detection member includes a plurality of detection electrodes, and the plurality of detection electrodes are disposed on the base substrate, At least one first detection electrode extending toward the other side of the base substrate; And at least one second detection electrode extending from the other side of the base substrate to a side of the base substrate through the lower portion of the channel, wherein the at least one first detection electrode and the at least one second detection electrode Can be arranged to be shifted from each other.

According to another aspect of the present invention, there is provided a method of manufacturing a blood testing apparatus, including: preparing a chamber element; And bonding the chamber element on a piezoelectric substrate, the step of fabricating the chamber element comprising: fabricating a master mold; Injecting a thermoset material into the master mold; Thermally curing the thermosetting material to form a chamber member; Separating the chamber member from the master mold; And bonding the chamber member onto the base substrate.

According to one aspect of the present invention, in the step of manufacturing the master mold, the master mold is provided with a protruding portion protruding upward, and a dome or hemispherical channel may be formed in the chamber member by the protrusion.

According to the chamber device, the blood test device including the chamber element, and the method of manufacturing the blood test device according to the embodiment, the surface acoustic waves are used to induce the micro-flow in the blood sample and control the intensity thereof, Can be effectively evaluated.

According to the chamber device, the blood testing device including the chamber device, and the method of manufacturing the blood testing device according to the embodiment, the degree of activation of the platelets can be controlled according to the magnitude of the AC voltage applied to the input electrode and the time of applying the AC voltage. And the flow direction can be controlled variously according to the frequency band.

According to the chamber device, the blood test device including the chamber element, and the method of manufacturing the blood test device according to the embodiment, it is possible to uniformly activate the platelets present in the blood sample, It is possible to more precisely detect the function and the degree of activation.

According to the chamber device, the blood test device including the chamber element, and the method of manufacturing the blood test device according to the embodiment, it is possible to perform reversible bonding on the piezoelectric substrate, It is possible to discard it after inspection and replace it with a new product.

According to the chamber element, the blood test apparatus including the chamber element, and the method of manufacturing the blood test apparatus according to the embodiment, the blood sample is held in the dome or hemispherical channel so that a high shear force or a high surface The acoustic waves (or sound power) can be effectively transmitted and the platelets can be rapidly concentrated.

According to the chamber element, the blood test apparatus including the chamber element, and the method of manufacturing the blood test apparatus according to the embodiment, the entire body can be downsized and the flow inside the blood sample can be easily controlled through electrical control.

According to the chamber device according to one embodiment, the function and activity of the platelet in the blood sample can be evaluated, as well as concentration and DNA amplification and concentration in various samples can be performed.

1 shows a blood testing apparatus according to an embodiment.
Fig. 2 is a sectional view of Fig. 1. Fig.
3A and 3B show a case where a transducer is provided as a parallel IDT.
4 shows a case where a transducer is provided as a slanted IDT.
Figures 5a and 5b illustrate the movement of particles in a sample by a gradient of hydrodynamic force.
6 is a flowchart showing a method of manufacturing a blood test apparatus according to an embodiment.
7 is a flowchart showing a method of manufacturing a chamber element.
8A to 8F show the manufacturing process of the chamber element.
9 is a flowchart illustrating a platelet function testing method using the blood testing apparatus according to an embodiment.
10A and 10B show the internal flow control of the blood sample by the control of the surface acoustic wave generating portion.
Figs. 11A to 11D show the state before and after activation of platelets.

Hereinafter, embodiments will be described in detail with reference to exemplary drawings. It should be noted that, in adding reference numerals to the constituent elements of the drawings, the same constituent elements are denoted by the same reference numerals even though they are shown in different drawings. In the following description of the embodiments, detailed description of known functions and configurations incorporated herein will be omitted when it may make the best of an understanding clear.

In describing the components of the embodiment, terms such as first, second, A, B, (a), and (b) may be used. These terms are intended to distinguish the constituent elements from other constituent elements, and the terms do not limit the nature, order or order of the constituent elements. When a component is described as being "connected", "coupled", or "connected" to another component, the component may be directly connected or connected to the other component, Quot; may be "connected," "coupled," or "connected. &Quot;

The components included in any one embodiment and the components including common functions will be described using the same names in other embodiments. Unless otherwise stated, the description of any one embodiment may be applied to other embodiments, and a detailed description thereof will be omitted in the overlapping scope.

1 is a cross-sectional view of FIG. 1, FIGS. 3A and 3B show a case where a transducer is provided as a parallel IDT, FIG. 4 is a cross- And Figures 5A and 5B illustrate the movement of particles in a sample by a gradient of hydrodynamic force.

1 and 2, a blood testing apparatus 10 according to an embodiment may include a piezoelectric substrate 100, a surface acoustic wave generator 200, a chamber element 300, and a cover 400.

Hereinafter, the case of measuring the activation or coagulation characteristics of platelets present in a blood sample, which is one of biomaterials, using the blood test apparatus 10 according to one embodiment will be described as an example.

At this time, an object to be detected in the blood sample may be platelets activated (or aggregated) by the platelet activating factor, and the degree of activation or aggregation of the platelets can be evaluated through the blood testing device 10 according to one embodiment .

The piezoelectric substrate 100 is a substrate provided with a piezoelectric material so that it can be converted into mechanical energy such as vibration when electric energy is applied. The piezoelectric material may be, for example, lithium niobate (LiNbO 3) or quartz . At this time, the piezoelectric substrate 100 may mechanically shrink or expand by applying electrical energy.

For example, the piezoelectric substrate 100 can be divided into two sections. In the first section of the piezoelectric substrate 100, the surface acoustic wave generating part 200 is disposed. In the second section of the piezoelectric substrate 100, (300) may be disposed.

At this time, on the outside of the surface acoustic wave generating part 200 in the first compartment of the piezoelectric substrate 100, an output member (not shown) for transmitting information on the electrical characteristics of the blood sample (BD in FIG. 2) measured in the chamber element 300 110 may be further disposed and the output member 110 may include a first output electrode 112 and a second output electrode 114, for example. The first output electrode 112 and the second output electrode 114 will be described in detail below.

As described above, on the piezoelectric substrate 100, a surface acoustic wave generating part 200 for generating surface acoustic waves may be disposed.

The surface acoustic wave generating unit 200 may include an input electrode 210 to which a voltage is applied and a transducer 220 that is electrically connected to the input electrode 210 and converts a voltage applied to the surface acoustic wave into a surface acoustic wave.

At this time, the input electrode 210 and the transducer 220 may be patterned on the piezoelectric substrate 100. For example, the input electrode 210 and the transducer 220 can be patterned on the piezoelectric substrate 100 in a desired form through a semiconductor etching process.

The plurality of input electrodes 210 may be formed to extend from one end of the piezoelectric substrate 100 toward the other end and may be disposed between the first output electrode 112 and the second output electrode 114. have.

Although not shown in detail, an input electrode 210 for generating surface acoustic waves and a first output electrode 112 or a second output electrode 114 for detecting the degree of activation or coagulation of platelets are connected to an electric control unit (not shown) Or a blood analysis unit (not shown), and the electric control unit or the blood analysis unit may be disposed on the piezoelectric substrate 100 or outside the piezoelectric substrate 100.

Since the input electrode 210 and the output member 110 do not interfere with the transducer 220 and the chamber element 300, the surface acoustic wave can be effectively controlled and the degree of activation or cohesion of platelets can be effectively measured.

A transducer 220 may be connected to the end of the input electrode 210.

For example, the transducer 220 may be an interdigital transducer. The transducer 220 may be designed in such a manner that electrodes with staggered fingers are disposed concentrically, and patterned on the piezoelectric substrate 100. [ can do. This can be referred to as an F-type transducer, which can be advantageous in that it can generate a concentrated surface acoustic wave that can apply a higher energy to the chamber element 300.

At this time, the number of electrode pairs constituting the transducer 220, the shape of the electrodes, the arrangement of the electrodes, and the like can be variously designed, so that the blood test apparatus 10 according to the embodiment can be optimized .

For example, as shown in FIG. 3A, the transducer 220 may be provided with a parallel IDT. The electrodes may be designed so that the electrodes with the staggered fingers arranged parallel to each other may be patterned on the piezoelectric substrate 100 have. This can be referred to as a P-type transducer, thereby generating a surface acoustic wave propagating toward the chamber element 300.

Alternatively, as shown in FIG. 3B, the transducer 220 may be provided as a plurality of parallel IDTs, and a plurality of parallel IDTs may be spaced apart from each other with the chamber element 300 therebetween, A surface acoustic wave can be generated.

1 and 2, one transducer 220 is illustrated as being disposed on the piezoelectric substrate 100. However, as shown in FIG. 3B, a pair of transducers or a plurality of pairs of transducers Lt; / RTI > can be arranged symmetrically or asymmetrically.

4, a transducer 220 may be provided as a slanted IDT, and an electrode of a shape in which fingers are staggered may be designed to be inclined toward the chamber element 300, and may be formed on the piezoelectric substrate 100 Patterning can be performed. This can be referred to as an S-type transducer, thereby generating a surface acoustic wave propagating toward the chamber element 300.

As described above, the shape or arrangement of the transducer 220 can be variously configured. When an AC voltage having a frequency corresponding to the shape or arrangement of the transducer 220 is applied to the input electrode 210, The surface acoustic wave propagating toward the chamber element 300 along the surface of the piezoelectric substrate 100 can be generated through the energy conversion of the piezoelectric material in the piezoelectric substrate 100.

At this time, the flow generated in the blood sample BD can be controlled by controlling the surface acoustic wave according to the magnitude of the AC voltage applied to the input electrode 210 and the time for applying the AC voltage, BD) can be controlled. The position where the surface acoustic wave is generated or the flow direction of the blood sample BD can be variously controlled according to the operating frequency of the electric energy applied to the input electrode 210 or the shape of the transducer 220.

Since the position of the surface acoustic wave generated by the surface acoustic wave generating part 200 can be predicted theoretically, the surface acoustic wave can be detected by positioning the chamber element 300 at a position corresponding thereto on the piezoelectric element 100, (BD).

Specifically, the acoustic output generated by the surface acoustic wave propagates a shear force to the blood sample BD injected into the chamber element 300 to generate an internal flow, whereby the blood sample BD is injected into the chamber element 300 Mixed, and concentrated in a < / RTI > At this time, the intensity of the surface acoustic wave may be determined by the shape or arrangement of the transducer 220, and may be finely controlled by controlling the electrical input value applied to the input electrode 210.

Therefore, in the blood test apparatus 10 according to the embodiment, it is not necessary to use an agitator for activating the platelets present in the blood sample BD, and the platelets can be more effectively activated using the surface acoustic waves.

Particularly, even when a plurality of chamber elements 300 are arranged on the piezoelectric substrate 100, the surface acoustic wave generating part 200 activates the platelets in the blood sample BD injected into the plurality of chamber elements 300 It is possible to miniaturize and simplify the blood test apparatus 10 according to one embodiment.

On the other hand, the chamber element 300 may be disposed on the piezoelectric substrate 100 to be spaced apart from the surface acoustic wave generating part 200.

The chamber element 300 may include a base substrate 310, a chamber member 320, a detection member 330, and an adsorption member 340.

The base substrate 310 may be reversibly bonded to the piezoelectric substrate 100.

For example, the base substrate 310 may be bonded to the piezoelectric substrate 100 with a coupling liquid CL such as water or an ultrasonic gel, and the base substrate 310 may be bonded to the piezoelectric substrate 100 Can be separated.

The base substrate 310 is bonded to the piezoelectric substrate 100 through the coupling liquid CL so that surface acoustic waves generated in the surface acoustic wave generating part 200 are transmitted to the chamber device 300 along the piezoelectric substrate 100, And can be transmitted from the piezoelectric substrate 100 to the base substrate 310 through the coupling liquid CL. The surface acoustic waves transmitted to the base substrate 310 may eventually be transmitted to the chamber member 320 and the blood sample BD injected into the chamber member 320.

In addition, the chamber member 320 may be disposed on the base substrate 310.

The injected blood sample BD may be retained in the chamber member 320 and the blood sample BD may be removed from the chamber member 320 after the blood test is completed.

Specifically, the chamber member 320 may include a channel 322, an injection compartment 324, and an exhaust compartment 326.

The channel 322 may be provided in a dome or hemispherical shape, for example, to be retained in the channel 322 implanted in the injection section 324.

Thereby, even when a strong surface acoustic wave or a strong acoustic output is transmitted, the blood sample BD can be stably maintained without being detached from the chamber element 300, effectively causing an internal flow in the blood sample BD. This can help to effectively activate the platelets present in the blood sample (BD).

The platelets present in the blood sample BD are generated by the shear stress generated when the surface acoustic wave generated in the surface acoustic wave generating part 200 flows near the wall surface of the channel 322 or the area where the surface acoustic wave is introduced into the chamber member 320 Lt; RTI ID = 0.0 > biophysical < / RTI >

Since the channel 322 is provided in the form of a dome or a hemisphere, the plasma 322 can be exposed for a longer time in the shear stress near the wall surface of the channel 322, so that the degree of activation of platelets can be evaluated more quickly.

More specifically, when an external force such as a surface acoustic wave acts on the sample, as shown in FIGS. 5A and 5B, the difference in hydrodynamic force acting on the particles in the sample (for example, P ₂ -P ₁ , P ₄ -P ₃ ), for example, particles may be generated where the hydrodynamic force acting on the particles is large (e.g., P ₂ , P ₄ ) (e.g., P ₁ , P ₃ ).

In order to induce a gradient of the hydrodynamic force for moving the particles as the particle size becomes smaller, it is necessary to induce a higher internal flow than when handling the micro-sized particles. In this case, If an external force such as a surface acoustic wave is strongly applied to the sample, the interface of the sample becomes unstable and it may be difficult to obtain a stable hydrodynamic force gradient.

On the other hand, if a sample, e.g., a blood sample BD, is held in the chamber member 320, and particularly in the channel 322 of the chamber member 320, a stable interface is created in the blood sample BD, A gradient in the hydrodynamic force can be induced for the blood sample BD due to the height difference of the blood sample BD.

Thus, in the process of inducing a fast velocity field or a fast internal flow to the blood sample BD by the surface acoustic wave or the like by the dome or hemispherical channel 322 in the chamber element 300, the gradient of stable interface and stable hydrodynamic force .

The injection section 324 may be formed to penetrate from the upper surface to the lower surface of the chamber member 320 and then communicate with one side of the channel 322. The injection compartment 324 may be spaced outwardly from directly above the top of the channel 322.

A blood sample BD mixed with a biochemical platelet activating inducer or a platelet activating factor (for example, ADP or the like) may be injected into the injection section 324, for example, A blood sample (BD) mixed with platelet activating factor can be injected into the platelet rich plasma. Further, the blood sample (BD) may be in a state of blood droplet.

The discharge compartment 326 may be formed so as to communicate with the other side of the channel 322 after being formed to penetrate from the upper surface to the lower surface of the chamber member 320 like the injection compartment 324. At this time, the discharge compartment 326 may be spaced outwardly from directly above the channel 322. Thus, the channel 322 may be disposed between the injection compartment 324 and the discharge compartment 326.

Further, the blood sample BD may be discharged to the outside after the blood test is completed through the discharge compartment 326. It is a matter of course that the blood sample BD held in the channel 322 can be discharged to the outside by disposing a vacuum suction device (not shown) in the discharge compartment 326 at this time.

The detection member 330 may be disposed on the base substrate 310.

The detecting member 330 is for detecting the degree of activation or coagulation of platelets present in the blood sample BD, for example.

Here, the case where the detecting member 330 detects a change in electrical characteristics due to activation or aggregation of the platelets present in the blood sample BD will be described as an example.

The detecting member 330 may be provided as an impedance electrode for measuring electrical resistance, for example.

Specifically, the detecting member 330 may include a plurality of detecting electrodes. For example, the plurality of detecting electrodes may include at least one first detecting electrode 332 and at least one second detecting electrode 334 can do.

The at least one first detection electrode 332 may extend from one side of the base substrate 310 toward the other side of the base substrate 310 and at least one second detection electrode 324 may extend from the base substrate 310 to the other side of the base substrate 310, The base substrate 310 and the base substrate 310 may be formed of the same material.

At this time, the at least one first detection electrode 332 and the at least one second detection electrode 334 may be spaced apart from one another. For example, at least one first detection electrode 332 and at least one second detection electrode 334 may be provided in a staggered manner.

In particular, at least one first detection electrode 332 and at least one second detection electrode 334 may be disposed below the dome or hemispherical channel 326 provided in the chamber member 320.

However, the configuration and arrangement of the plurality of detection electrodes are not limited to this, and if the characteristics of the blood sample (BD) can be measured, for example, a change in electrical characteristics due to activation or aggregation of platelets present in the blood sample (BD) Either is possible.

The plurality of detection electrodes are connected to the ends of at least one first detection electrode 332 and include a third detection electrode 336 extending toward the end of the chamber member 320 on the base substrate 310 and at least one And a fourth detection electrode 338 connected to an end of the second detection electrode 334 of the chamber member 320 and extending toward the end of the chamber member 320 on the base substrate 310.

The third detection electrode 336 and the fourth detection electrode 338 are electrically connected to at least one first detection electrode 332 and at least one second detection electrode 334, To the output member (110) disposed on the piezoelectric substrate (100).

Specifically, the end of the third detection electrode 336 may be connected to the first output electrode 112 and the end of the fourth detection electrode 338 may be connected to the second output electrode 114.

The third detection electrode 336 and the fourth detection electrode 338 may be coupled to or separated from each other with respect to the first output electrode 112 and the second output electrode 114.

This is for facilitating the replacement of the chamber element 300 on the piezoelectric substrate 100, whereby the chamber element 300 can be used in a disposable type.

For example, a hinge H may be connected to the end of the third detecting electrode 336 and the end of the fourth detecting electrode 338, and the end of the hinge H may be connected to the first output electrode 112 and the second The end of the hinge H can be lifted after disengaging from the output electrode 114 to completely separate the chamber element 300 from the piezoelectric substrate 100. [

A protrusion is formed on an end of the third detecting electrode 336 and an end of the fourth detecting electrode 338. The first output electrode 112 and the second output electrode 114 are provided with grooves into which the protrusions can be inserted So that the third detection electrode 336 and the fourth detection electrode 338 can be coupled to or separated from the first output electrode 112 and the second output electrode 114.

Alternatively, the third detecting electrode 336 and the fourth detecting electrode 338 may be connected to the outer surface of the piezoelectric substrate 100 separately from the first output electrode 112 and the second output electrode 114, It is a matter of course that the member of the present invention can be mounted.

The chamber element 300 may be electrically connected to the piezoelectric substrate 100. The chamber element 300 may be electrically connected to the first output electrode 112 through the first detection electrode 332, And if the electric characteristic value measured at the at least one second detection electrode 334 can be output to the outside through the second output electrode 114, the third detection electrode 336 and the fourth detection electrode 338 and the first output electrode 112 and the second output electrode 114 may be combined or separated.

However, although not specifically shown, the first output electrode 112 and the second output electrode 114 are not disposed on the piezoelectric substrate 100, and the third detection electrode 336 and the fourth detection electrode 338 ) May be directly connected to the direct blood analysis unit (not shown).

As described above, the method of measuring the degree of activation or aggregation of the platelets from the microscopic difference of the electrical resistance in the detecting member 330 requires a finer size and a smaller amount of platelets than the optical-based turbidity measuring method or the method of blocking the microfluidic channel The degree of activation or the degree of coagulation of the protein can be detected with high accuracy.

On the other hand, the adsorption member 340 may be disposed on the at least one first detection electrode 332 and the at least one second detection electrode 334 described above.

The adsorbing member 340 may be formed of, for example, a reaction protein such as collagen, or a von Willebrand factor (Vwf), from which activated platelets can be adsorbed when platelets are activated.

At this time, the adsorption member 340 may be continuously or intermittently coated on the surfaces of the at least one first detection electrode 332 and the at least one second detection electrode 334, and may be coated with a single layer or multiple layers .

When the activated platelets are adsorbed to the adsorbing member 340 by the adsorbing member 340 being disposed on at least one of the first detecting electrodes 332 and the at least one second detecting electrode 334, 1 detection electrode 332 and the at least one second detection electrode 334 can be changed.

For example, when the activated platelets are highly adsorbed to the adsorbing member 340, the magnitude of the resistance detected by the at least one first detection electrode 332 or the at least one second detection electrode 334 may be relatively large And the activated platelets are less adsorbed to the adsorbing member 340, the magnitude of the resistance detected by the at least one first detection electrode 332 or the at least one second detection electrode 334 may be relatively small.

Thus, by analyzing the signals detected by the at least one first detection electrode 332 and the at least one second detection electrode 334, the degree of activation or aggregation of the platelets present in the blood sample BD can be evaluated.

At this time, at least one first detection electrode 332 and at least one second detection electrode 334 are disposed below the dome or hemispherical channel 326 provided in the dome chamber member 320, as described above, The adsorption member 340 is also disposed below the dome or hemispherical channel 326 provided in the dome chamber member 320 so that when an internal flow occurs in the blood sample BD by the surface acoustic wave, The chance of contact with the adsorbing member 340 can be increased and the degree of platelet aggregation or degree of coagulation of platelets can be detected more precisely.

The arrangement or configuration of the detecting member 330 and the adsorbing member 340 described above is not limited to this, and any of them can be used as long as it can effectively measure the degree of activation or aggregation of the platelets present in the blood sample BD.

Here, the detection member 330 and the adsorption member 340 are disposed on the base substrate 310 in order to evaluate the degree of activation or coagulation of the platelets through the difference in electrical resistance. However, in some cases, 310 and the chamber member 320 so that the activated platelets can be used to adsorb the activated platelets to the adsorption member 340. [ At this time, the activated platelets adsorbed on the adsorption member 340 can be measured for the degree of activation or coagulation by an optical measuring method.

In addition, the piezoelectric substrate 100, the surface acoustic wave generating part 200, and the chamber element 300 can be sealed by the cover 400.

At this time, the cover 400 can completely or partially seal the piezoelectric substrate 100, the surface acoustic wave generating part 200, and the chamber element 300, so that the blood sample BD held in the chamber element 300, The external influence on the ducer 220 can be blocked.

Hereinafter, a method of manufacturing a blood test apparatus according to an embodiment of the present invention will be described.

FIG. 6 is a flowchart showing a method of manufacturing a blood testing apparatus according to an embodiment, FIG. 7 is a flowchart showing a method of manufacturing a chamber element, and FIGS. 8A to 8F show a manufacturing process of a chamber element.

In particular, with reference to FIG. 6, a blood testing apparatus according to an embodiment can be manufactured as follows.

First, a chamber device is manufactured (S10).

Particularly, referring to Figs. 7 and 8, a chamber element can be manufactured as follows.

First, a master mold is manufactured (S11).

8A, the master mold M may be manufactured based on 3D printing, and the master mold M may be provided with a protrusion C for forming a dome-shaped or hemispherical channel 322 at a later stage .

It is of course also possible for the master mold M to be provided with additional protrusions for forming an injection section for injecting a blood sample into the chamber member 320 or an ejection section for ejecting the blood sample.

Then, a thermosetting material is injected into the master mold (S12), and the thermosetting material is cured to manufacture a chamber member (S13).

The thermosetting material A may be filled in the master mold M as shown in FIG. 8B, and the thermosetting material A may be thermoset as shown in FIG. 8C.

At this time, thermal deformation may occur at the time of thermal curing according to the characteristics of the thermosetting material (A), so that the thermosetting material (A) can be thermally cured after predicting thermal deformation in advance by using computer simulation.

Through this process, the chamber member 320 can be manufactured by the master mold M. [

Then, the chamber member is separated from the master mold (S14).

8D, when the chamber member 320 is separated from the master mold M, a dome or hemispherical channel 322 is formed in the chamber member 320 by the protrusion C in the master mold M, Can be formed.

Finally, the chamber member is bonded onto the base substrate (S15).

At this time, when the chamber member 320 is bonded onto the base substrate 310 as shown in FIG. 8E, the lower surface of the chamber member 320 can be smoothly surface-treated.

Further, on the base substrate 310, detection electrodes are previously patterned, and the adsorption member may be coated on the surface of the detection electrode.

On the other hand, the angle between the base substrate 310 and the channel 322 at the portion where the base substrate 310 contacts the dome or hemispherical channel 322 may affect the performance of the chamber element. That is, by optimizing the angle between the base substrate 310 and the channel 322, it is possible to effectively activate / agglomerate, amplify, or concentrate various samples including blood samples or the like held in the channels 322.

As a result, a chamber element is manufactured as shown in FIG. 8F.

Then, the chamber element is bonded onto the piezoelectric substrate (S20).

At this time, the chamber element can be reversibly bonded to the piezoelectric substrate through the coupling liquid, and the chamber element can be separated from the piezoelectric substrate and the new chamber element can be bonded to the piezoelectric substrate after completion of the blood test.

Finally, the chamber element is electrically connected to the piezoelectric substrate (S30).

For example, by connecting a detection electrode, which is provided in the chamber device and detects the characteristics of blood, to the output electrode provided on the piezoelectric substrate, the electrical characteristic value of the blood detected in the chamber device can be transmitted to the blood analyzer .

However, this step is not essential, and this step may be omitted if the output electrode is not disposed on the piezoelectric substrate in some cases, and the electrical characteristic value of the blood detected in the chamber element is directly transmitted to the blood analysis unit.

Hereinafter, a platelet function testing method using the blood test apparatus according to one embodiment will be described.

FIGS. 9A and 9B are flow charts illustrating a platelet function testing method using the blood testing apparatus according to an embodiment. FIGS. 10A and 10B show the internal flow control of a blood sample by controlling the surface acoustic wave generator, Of FIG.

Referring to FIG. 9, a platelet function test may be performed as follows using the blood test apparatus according to one embodiment.

First, a platelet activating factor is injected into a blood sample (S100).

For example, a blood sample may be prepared as platelet-rich plasma, and the platelet activating factor may be provided by ADP or the like capable of coagulating or activating platelets.

Subsequently, a blood sample is injected into the above-mentioned chamber element (S200).

Specifically, a blood sample mixed with a platelet activating factor is injected into an injection compartment provided in the chamber element. At this time, since the dome or hemispherical channel is communicated to the injection section, the blood sample injected into the injection section can eventually be held in the dome or hemispherical channel.

Then, a surface acoustic wave is generated in the surface acoustic wave generating portion (S300).

Surface acoustic waves may be generated in the transducer by the applied electric energy, and a high shear flow may be generated in the blood sample by the surface acoustic wave.

At this time, depending on the frequency band of the applied electric energy as shown in Figs. 10A and 10B, the direction of flow seen as rotation of 10 mu m particles floating in the blood sample can be reversely controlled.

By controlling the magnitude of the AC voltage applied to the transducer, the time for applying the AC voltage, and the like, the surface acoustic wave can be controlled, thereby controlling the internal flow of the blood sample.

In addition, since the blood sample is mixed with the platelet activating factor by the surface acoustic wave generated in the surface acoustic wave generating part, the platelets present in the blood sample can be activated by the platelet activating factor, so that the degree of activation or coagulation Can be adjusted.

11A and 11B are photographs of blood samples taken at 4x magnification. Cells existing in the blood sample before platelet activation were not observed. However, when a surface acoustic wave generated by applying an AC voltage of 19 V was applied to the blood sample for 1 minute , And activated platelets were observed.

11C and 11D are photographs of blood samples taken at a magnification of 40x. Inactivation platelets individually present in the blood sample were observed before activation of the platelets. Platelet activation and aggregation Platelets are observed, and the size becomes larger as the platelets aggregate.

As a result of this experiment, it was confirmed that the flow in the blood sample induced by the concentrated surface acoustic wave generated in the transducer is sufficient to apply the minimum critical shear rate required for platelet activation of 3100 s ^-1 .

Then, the electrical property or the optical property according to the platelet aggregation is measured (S400), and the platelet aggregation is evaluated (S500).

Specifically, the platelets activated by the detecting member and the adsorbing member provided in the chamber element are adsorbed on the adsorbing member, thereby changing the electrical characteristic value detected by the detecting member. The platelet aggregation degree or the degree of activation Can be evaluated.

In addition, after the activated platelets are adsorbed on the adsorbing member, the platelet aggregation degree or activity can be evaluated by changing the optical property value by measuring the optical property using the optical device.

As described above, the chamber device and the blood testing device including the chamber device according to an embodiment can induce micro-flow in the blood sample using the surface acoustic wave and can control the intensity thereof to effectively evaluate the degree of activation of platelets in the blood sample The platelets present in the blood sample can be uniformly activated and the function and activity of platelets can be detected more precisely based on the minute difference in electrical resistance.

In particular, the blood sample is maintained in a dome or hemispherical channel so that a high shear force or a high surface acoustic wave (or acoustic power) can be effectively delivered to the blood sample and the platelets can be rapidly concentrated.

Accordingly, the chamber device according to one embodiment and the blood testing device including the chamber device can perform various tests on various samples as well as an evaluation of the function and activity of platelets.

For example, the sample may be a blood sample containing DNA, the detection target in the sample may be concentrated or amplified DNA, and the DNA in the blood sample may be concentrated or expanded using surface acoustic waves to remove the DNA The degree of concentration or amplification can be assessed.

Specifically, by using the acoustic heating effect generated by the surface acoustic wave, the DNA can be amplified by isothermal and the micro-mixing effect generated by the surface acoustic wave can be simultaneously used to form the existing thermoelectric device DNA can be amplified in a larger amount than the PCR used.

At this time, the chamber device according to the embodiment and the blood test apparatus including the chamber device can not only apply a strong and stable hydrodynamic force in the blood sample to cover the oil to prevent evaporation of the blood sample, , Fluorescence-stained DNA can be concentrated in the DNA amplification process using the temperature, which can be useful for molecular diagnosis of a leaner detection target.

Further, the sample may be a microdroplet containing a virus or a bacteria, and the object to be detected in the sample may be a concentrated virus or bacteria, and the chamber device according to an embodiment and the blood testing device including the chamber element may be a surface acoustic wave Can be used for clinical diagnosis of particles having a size of several hundred nanometers or less because the virus or bacteria can be concentrated at high speed.

Although the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, And various modifications and changes may be made thereto without departing from the scope of the present invention. Accordingly, the spirit of the present invention should not be construed as being limited to the embodiments described, and all of the equivalents or equivalents of the claims, as well as the claims set forth below, fall within the scope of the present invention.

10: Blood testing device
100: piezoelectric substrate
200: Surface acoustic wave generating part
300: chamber element
400: cover

Claims (12)

A piezoelectric substrate;
A surface acoustic wave generating unit disposed on the piezoelectric substrate to generate a surface acoustic wave; And
A chamber element disposed on the piezoelectric substrate, the chamber element being spaced apart from the surface acoustic wave generating portion and transmitting surface acoustic waves generated from the surface acoustic wave generating portion;
Lt; / RTI >
Wherein a surface acoustic wave generated in the surface acoustic wave generating unit generates an internal flow in a blood sample,
Wherein the chamber element comprises:
A chamber member for retaining a blood sample therein, the chamber member having a dome or hemispherical channel formed therein, the chamber member having the blood sample held in the dome or hemispherical channel;
A base substrate disposed below the chamber member; And
A detection electrode disposed on the base substrate and detecting electrical characteristics of a detection target in the blood sample; / RTI >
Wherein the detection electrode is disposed under the dome or hemispherical channel,
Wherein the detection electrode is provided with an adsorbent material to which the detection target in the blood sample is adsorbed and adsorbed on the adsorbent material while the detection target in the blood sample circulates in the chamber member by the surface acoustic wave generated in the surface acoustic wave generator, The blood test device.
delete delete The method according to claim 1,
Wherein the base substrate is reversibly bonded to the piezoelectric substrate by a coupling liquid so that surface acoustic waves generated in the surface acoustic wave generating portion are transmitted to the blood sample held in the chamber member through the coupling liquid, Device.
The method according to claim 1,
Wherein the piezoelectric substrate is provided with an output electrode electrically connected to the detection electrode and transmitting electrical characteristics of the blood sample detected by the detection electrode,
And the end of the detection electrode and the output electrode can be coupled or separated from each other.
delete The method according to claim 1,
Wherein the surface acoustic wave generating unit comprises:
An input electrode to which electrical energy is applied; And
A transducer electrically connected to the input electrode to convert applied electric energy into a surface acoustic wave;
Lt; / RTI >
Wherein the input electrode and the transducer are patterned on the piezoelectric substrate,
Wherein flow characteristics of the blood sample are controlled by controlling electric energy applied to the electrode.
A base substrate; And
A chamber member disposed on the base substrate and into which a sample is injected;
Lt; / RTI >
Wherein the chamber member comprises:
A channel provided in the form of a dome or hemisphere to hold the sample therein;
/ RTI >
Wherein a gradient of a hydrodynamic force is generated in the sample due to a height difference of the sample in the channel when an external force is applied to generate an internal flow in the sample.
9. The method of claim 8,
Wherein the chamber member comprises:
An inlet section communicating with the channel to inject the sample; And
A discharge compartment communicating with the channel to discharge the sample;
Further comprising:
Wherein the channel is disposed between the inlet section and the outlet section.
9. The method of claim 8,
An adsorption member disposed on the base substrate for adsorbing an object to be detected in the sample; And
A detecting member disposed between the base substrate and the adsorption member;
Further comprising:
Wherein the detection member includes a plurality of detection electrodes,
Wherein the plurality of detection electrodes comprise:
At least one first detection electrode extending from one side of the base substrate to the other side of the base substrate through the channel bottom; And
At least one second detection electrode extending from the other side of the base substrate to the one side of the base substrate through the channel bottom;
/ RTI >
Wherein the at least one first detection electrode and the at least one second detection electrode are disposed to be shifted from each other.
Fabricating a chamber element; And
Bonding the chamber element to a piezoelectric substrate;
Lt; / RTI >
Wherein the step of fabricating the chamber element comprises:
Producing a master mold;
Injecting a thermoset material into the master mold;
Thermally curing the thermosetting material to form a chamber member;
Separating the chamber member from the master mold; And
Bonding the chamber member onto a base substrate;
The method comprising the steps of:
12. The method of claim 11,
In the step of producing the master mold,
The master mold is provided with a projection projecting upwardly,
And a dome or hemispherical channel is formed in the chamber member by the projecting portion.

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