IE87076B1

IE87076B1 - Surface plasmon resonance sensor device using microfluidic channel and system comprising the same

Info

Publication number: IE87076B1
Application number: IE20170055A
Authority: IE
Inventors: Lee Seungki; Jeong Daehong; Lee Hoyoung; Park Jaehyoung; Kim Hyeongmin
Original assignee: Univ Dankook Iacf
Priority date: 2016-12-12
Filing date: 2017-03-07
Publication date: 2019-12-25
Also published as: KR101847745B1

Abstract

Disclosed is a fiber-optic surface plasmon resonance sensor device capable of multi-sensing. The fiber-optic surface plasmon resonance sensor device includes: a channel unit including one or more microfluidic channels formed in a body thereof and a plurality of sensor insertion holes, wherein each of the microfluidic channels includes a plurality of solution inlets and one or more solution outlets, and the sensor insertion holes are formed from the outside and connected with the one or more microfluidic channels; and a plurality of fiber-optic localized surface plasmon resonance sensors, each of which is inserted into each of the plurality of sensor insertion holes. Each of the fiber-optic localized surface plasmon resonance sensors can include metal nanoparticles and an antibody bound to the metal nanoparticles, wherein the resonance wavelengths of the metal nanoparticles and the type of the antibody are different for each sensor. <Figure 1>

Description

BACKGROUND 1. Technical Field Example embodiments of the present invention relate in general to the ﬁeld of surface plasmon resonance sensors, and more specifically to a ﬁber-optic surface plasmon resonance sensor device capable of multi-sensing by including one or more microﬂuidic channels and a system including the ﬁber-optic surface plasmon resonance sensor device. 2. RelatedArt Localized surface plasmon resonance is a phenomenon that occurs when a metal nanoparticle or nanostructure interacts with light. Since wavelengths at which the localized surface plasmon resonance occurs depend on the material, size, or shape of the metal nanoparticles, it may be possible to make localized surface plasmon resonance occur at desired wavelengths within a visible light or near-infrared region. One of the important characteristics of localized surface plasmon resonance is that such resonance is sensitively affected by a change in the refractive index of a surrounding medium. A change in the surrounding medium brings a change to wavelengths at which absorption and scattering occur or intensities of absorption and scattering, and such a characteristic is applied as the basis of a sensor.

Conventional multi-sensing devices taking advantage of the localized surface plasmon resonance include a substrate therein, and, strictly speaking, are based on the concept of multi-spotting rather than multiplexing. Such devices have a chip structure with multiple channels formed thereon, and a measuring process thereof involves conducting measurement at multiple sites. Therefore, the shortening of diagnosis time, which is an advantage of multi-sensing, cannot be expected with such devices. The optical system is complex due to the nature of a substrate-based structure, and constructing such a complex optical system is costly. Also, when a microﬂuidic charmel is formed on a chip, observations should be made through the charmel, involving much noise and mechanical constraints (e.g. length of observation of the microscope, etc.). Further, when a microﬂuidic channel is not formed on a chip, an object to be measured may be affected by external environmental factors such as sample contamination or evaporation.

Also, there are multi-charmel spectroscopes connected with a plurality of optical ﬁbers, but such spectroscopes are limited in terms of the method of detecting signals in a detection unit.

[Conventional Art Documents 1 [Patent documentl (Patent document 1) Korean Patent Application No. 100028287 SUMMARY Accordingly, example embodiments of the present invention are provided to substantially obviate one or more problems due to limitations and disadvantages of the related art, and provide a surface plasmon resonance sensor device that includes a channel unit having one or more microﬂuidic channels.

Also, example embodiments of the present invention provide a surface plasmon resonance sensor system that includes the sensor surface plasmon resonance sensor device.

In some example embodiments, a surface plasmon resonance sensor device includes: a channel unit including: one or more microﬂuidic channels formed in a body thereof; and a plurality of sensor insertion holes, wherein each of the one or more microﬂuidic channels includes a plurality of solution inlets and one or more solution outlets, and the sensor insertion holes are formed from an outside and connected with the one or more microﬂuidic channels; and a plurality of ﬁber-optic localized surface plasmon resonance sensors, each of which is inserted into each of the plurality of sensor insertion holes.

Each of the plurality of ﬁber-optic localized surface plasmon resonance sensors includes metal nanoparticles on a surface of a core of a front end portion, wherein the front end portion is inserted into each of the plurality of sensor insertion holes.

The channel unit includes a plurality of microﬂuidic channels in a body thereof, wherein the plurality of microﬂuidic channels are separate from one another and each of the plurality of microﬂuidic charmels includes a solution inlet and a solution outlet.

The plurality of sensor insertion holes are formed laterally or vertically.

Each of the plurality of ﬁber-optic localized surface plasmon resonance sensors may include metal nanoparticles, and resonance wavelengths of the metal nanoparticles may be different for each of the plurality of ﬁber-optic localized surface plasmon resonance sensors.

Each of the plurality of ﬁber-optic localized surface plasmon resonance sensors may include an antibody bound to the metal nanoparticles, and the antibody may be different for each of the plurality of ﬁber-optic localized surface plasmon resonance sensors.

In other example embodiments, a surface plasmon resonance sensor system includes: a charmel unit including: one or more microﬂuidic channels formed in a body thereof; and a plurality of sensor insertion holes, wherein each of the one or more microﬂuidic channels includes x (X22) solution inlets and y (yzl) solution outlet(s), and the plurality of sensor insertion holes are connected with the one or more microﬂuidic channels from an outside; a plurality of ﬁber-optic localized surface plasmon resonance sensors, each of which is inserted into each of the plurality of sensor insertion holes and includes metal nanoparticles on a front end thereof; a solution injection unit connected with the solution inlets to enable an injection of each solution into each of the solution inlets; and one or more optical measuring units connected with the plurality of ﬁber-optic localized surface plasmon resonance sensors.

Each of the one or more optical measuring unit includes a light source and a detector connected with one of the ﬁber-optic localized surface plasmon resonance sensors corresponding to the optical measuring unit via a multimode optical ﬁber coupler.

The solution injection unit includes: tubes, each of which can be connected with each of the solution inlets from one end; and a pumping device for supplying test solutions from the other end, wherein each of the tubes is equipped with a shutoff valve capable of opening and closing the tube.

Each of the plurality of ﬁber-optic localized surface plasmon resonance sensors may include an antibody bound to metal nanoparticles, and the antibody may be different for each of the plurality of ﬁber-optic localized surface plasmon resonance sensors.

Example embodiments of the present invention provide a ﬁber-optic localized surface plasmon resonance sensor device and system that are capable of multi-sensing. By including a channel unit having a variety of microﬂuidic channels, the sensor device and system are capable of multi—sensing in various ways, and thus enable fast and accurate measurement. The microﬂuidic charmels in such a channel unit can provide an environment for reliable measurement, result in higher cost efﬁciency, lower optical loss, higher sensitivity, and more simple optical system conﬁgurations compared to conventional substrate-based structures, and are preferably used for label-free immunoassays. Moreover, since light from a light source travels through optical ﬁbers, possible damage to biomolecules can be minimized. Further, the channel unit including the microﬂuidic channels is fabricated using a bio-friendly PDMS material, and thus can be widely used for conventional microﬂuidic devices, micro total analysis system (TAS) devices, and the like. Since the channel unit is also fabricated using a mold consisting of a silicon-based material, the fabrication thereof is easy and reproducible. By taking advantage of multi-sensing, the device and system according to example embodiments of the present invention can be applied for novel drug screening, which requires much time to search for a candidate material, and also for early diagnosis, which is the biggest obstacle to infectious disease treatment. When structural integration is accomplished, the device and system according to example embodiments of the present invention can become competitive in the market of POC biosensors capable of identifying speciﬁc diseases instantly.

BRIEF DESCRIPTION OF DRAWINGS Example embodiments of the present invention will become more apparent by describing in detail example embodiments of the present invention with reference to the accompanying drawings, in which: FIG. 1 is a schematic view of a surface plasmon resonance sensor system according to an example embodiment of the present invention; FIGS. 2A to 2D illustrate Example 1 of a surface plasmon resonance sensor device according to example embodiments of the present invention; FIG. 3 illustrates Example 1 of a surface plasmon resonance sensor device according to example embodiments of the present invention; FIG. 4 illustrates Example 2 of a surface plasmon resonance sensor device according to example embodiments of the present invention; FIG. 5 shows an example of a surface plasmon resonance sensor device according to example embodiments of the present invention inserted in various directions; FIGS. 6 to 8 illustrate an exemplary fabrication process of a channel unit applied to a surface plasmon resonance sensor device according to example embodiments of the present invention; FIG. 9 illustrates a ﬁber-optic localized surface plasmon resonance sensor applied to a surface plasmon resonance sensor device according to an example embodiment of the present invention; FIG. 10 illustrates a manufacturing process of a fiber-optic localized surface plasmon resonance sensor applied to a surface plasmon resonance sensor device according to an example embodiment of the present invention and also provides an image of the ﬁber-optic localized surface plasmon resonance sensor; FIG. 11 shows examples of a ﬁber-optic localized surface plasmon resonance sensor applied to a surface plasmon resonance sensor device according to an example embodiment of the present invention; and FIG. 12 shows an application example of sensor manufacturing using a channel unit applied to a surface plasmon resonance sensor device according to an example embodiment of the present invention.

DESCRIPTION OF EXAMPLE EMBODIMENTS Hereinafter, example embodiments of the present invention will be described in detail with reference to the accompanying drawings. In describing example embodiments of the present invention, detailed descriptions of related well-known functions or conﬁgurations deemed to unnecessarily obscure the gist of the present invention will be omitted.

There are multiple biomarkers for one disease, and a disease cannot be accurately diagnosed with only one biomarker. Also, searching for the best candidate material to react with a biomarker requires the testing of multiple candidate materials. Therefore, multi- sensing techniques are required in the ﬁeld of novel drug screening and diagnosis. Sensor characteristics required in this ﬁeld include multiplicity, which is an ability to simultaneously analyze various biomarkers; speciﬁcity, which requires high selectivity to a target; high sensitivity for analyzing a trace amount of a biomarker; and an ability to perform quantitative analysis to quantify various types of biomarkers. Example embodiments of the present invention relate to the ﬁeld of ﬁber-optic localized surface plasmon resonance sensors in which one or more microﬂuidic channels are used, wherein the sensors are intended to perform label-free, real-time, and multi—sensing of various biological and chemical materials.

Example embodiments of the present invention provide: a surface plasmon resonance sensor device that includes a microﬂuidic channel units; a method of manufacturing a channel unit; and a surface plasmon resonance sensor system.

[Surface plasmon resonance sensor device] The surface plasmon resonance sensor device 1 according to an example embodiment of the present invention includes a charmel unit 11; and ﬁber-optic localized surface plasmon resonance sensors 17 inserted into sensor insertion holes 119 in the channel unit 11.

The channel unit 11 includes one or more microﬂuidic charmels 117, each of which includes x (X22) solution inlets 113 and y (yzl) solution outlet(s) 115, formed in a body thereof; and z (222) sensor insertion holes 119 connected with the one or more microﬂuidic channels 1 17.

Each ﬁber-optic localized surface plasmon resonance sensor 17 inserted into each of the sensor insertion holes 119 may include metal (e.g. gold or silver) nanoparticles on the core of a front end thereof, which is the sensor part that is inserted into each of the sensor insertion holes 119. Each of the sensors 17 may have different resonance wavelengths of metal nanoparticles immobilized on the core thereof. In other words, there may be “n” ﬁber-optic localized surface plasmon resonance sensors, each of which includes nanoparticles having a resonance wavelength required for multi-sensing and an antibody bound to the nanoparticles, in which case, the resonance wavelengths of the nanoparticles and the type of the antibody bound to the nanoparticles may be different for each sensor. Alternatively, the ﬁber—optic localized surface plasmon resonance sensors being discussed in this section may be ﬁber-optic localized surface plasmon resonance sensors including gold nanoparticles, wherein the size and shape of the gold nanoparticles are different for each sensor depending on a patterning process or concentration of N-(2-Hydroxyethyl)piperazine-N’-(2- ethanesulfonic acid) (HEPES).

Hereinafter, the same reference numeral will be assigned to the same or similar elements.

Example 1 FIGS. 2A to 2D illustrate Example 1 of a surface plasmon resonance sensor device according to example embodiments of the present invention. FIG. 2A is a perspective View, FIG. 2B is an exploded perspective view, FIG. 2C is a plan View is and FIG. 2D is a cross- sectional view along line A-A’ of FIG. 2C.

Example 1 of the surface plasmon resonance sensor device includes a channel unit 11 having a plurality of solution inlets 113, a solution outlet 115, and a plurality of sensor insertion holes 119. As shown in FIGS. 2A to 2D, microﬂuidic charmel(s) 117 connecting the plurality of solution inlets 113 with the solution outlet 115 may include a reaction chamber 118. Sensor insertion holes 119 are connected with this reaction chamber 118 so that front ends of sensors inserted into the sensor insertion holes 119 are exposed and contact solutions in the reaction chamber 118.

Each ﬁber-optic localized surface plasmon resonance sensor 17 is inserted into each of the sensor insertion holes 119 and is exposed within the microﬂuidic channel(s) 117, i.e., within the reaction chamber 118.

The plurality of solution inlets 113 may be branched from the reaction chamber 118 or a channel portion extended from the reaction chamber 118.

As clearly shown in FIG. 2B and will be described in more detail below, the channel unit 11 may be fabricated by combining an upper layer U formed by molding and a bottom layer B made of glass. The ﬁber-optic localized surface plasmon resonance sensors 17 may be inserted into grooves in the upper layer U, which later become the sensor insertion holes 119 when the upper layer U and the bottom layer B are combined through adhesion.

According to the conﬁguration of Example 1 as illustrated in drawings, the plurality of ﬁber-optic localized surface plasmon resonance sensors 17 include the metal nanoparticles that are different for each sensor, and thus enable simultaneous measurement of various signals.

Example 2 FIG. 4 illustrates Example 2 of a surface plasmon resonance sensor device according to example embodiments of the present invention.

A charmel unit 11 of Example 2 includes a plurality of microﬂuidic channels 117, which are separate from one another. Each of the separate microﬂuidic charmels 117 includes a solution inlet 113 and a solution outlet 115. Also, each of the separate microﬂuidic channels 117 is connected with a corresponding sensor insertion hole 119. At each sensor insertion hole 119, a ﬁber-optic localized surface plasmon resonance sensor 17 is inserted.

Since the channels are separate from one another in the conﬁguration of Example 2, channel contamination may be minimized by different solutions entering into different inlets.

In other words, in the conﬁguration of Example 2, localized surface plasmon resonance wavelengths of nanoparticles and types of an antibody bound to the nanoparticles are different for each sensor. Such a conﬁguration is suitable when the measurement of multiple objects is intended and can be repeatedly fabricated by using suitable molds, which allows to be preferably used for identifying a cause of disease in multiple patients.

As shown in FIG. 5, the channel unit 11 applied to the surface plasmon resonance sensor devices according to Examples 1 and 2 may be fabricated in a lateral form (FIG. 5(a)) as described above or a vertical form as in FIG. 5(b). In this case, the type (form) of the channel unit 11 being lateral or vertical is determined by a direction (lateral or vertical) in which the ﬁber-optic localized surface plasmon resonance sensors 17 are inserted.

In the vertical form as shown in FIG. 5(b), the ﬂuid moves along the side of an optical ﬁber rather than across the sensor surface. Since the diameter of the reaction chamber 118 is 25 times greater than the charmel height, it requires high pressure for the ﬂuid to pass through such a narrow region. This explains why the ﬂow is generated along the side of an optical ﬁber, where the ﬂuid can move with a relatively low pressure. This suggests that, when a sensor is positioned inside a channel, a reaction is induced by slow diffusion due to a difference in concentration, not by a ﬂuid ﬂow in a direct manner at a sensor surface. Also suggested is that, when air bubbles or nonspeciﬁc binding is generated around the sensor, there is only little ﬂow toward the sensor surface, resulting in the removal of air bubbles or washing of nonspeciﬁc binding at a low level.

In the lateral form as shown in FIG. 5(a), when there is a constant ﬂow toward the sensor surface as generated by a ﬂuid supplied at a constant rate, biomolecular material transfer caused by the ﬂow becomes directional such that reactions involving biomolecular materials of the same concentration can take place repeatedly at a sensor surface. In this way, more binding opportunities will be provided to sensors, given the same sensor surface area. Also, the ﬂow generated at the surface enables the washing of weak nonspeciﬁc binding with a buffer solution, thereby ensuring signal reproducibility.

[Manufacturing of sensor device] FIGS. 6 to 8 illustrate an exemplary fabrication process of a channel unit applied to a surface plasmon resonance sensor device according to example embodiments of the present invention.

The method of fabricating the channel unit 11 according to example embodiments of the present invention includes forming a mold M having an embossed structure as shown in FIGS. 6(a) to 6(c).

First, a mask 71 is fonned on a silicon substrate 70 through a photolithography process as shown in FIG. 6(a). The mask 71 may be made of a photoresist as illustrated in FIG. 6(a) or other material. Subsequently by etching the silicon substrate 70 (FIG. 6(b)) and then removing the mask 71, a mold M with an embossed structure 72 is obtained as illustrated in FIG. 6(0). The embossed structure 72 may include embossed microﬂuidic channel structures for forming grooves for solution inlets 113, a solution outlet 115, and the reaction chamber 118, and embossed sensor insertion hole structures for forming grooves for the sensor insertion holes 119.

The other type of material composing the mask may be a silicon oxide ﬁlm. For this, a silicon oxide ﬁlm is applied on the silicon substrate 70 and a photoresist mask is formed on the silicon oxide ﬁlm, and the silicon oxide ﬁlm is anisotropically etched and then the photoresist mask is removed to prepare the silicon oxide mask. Subsequently, about 250 mm of the thickness of the silicon substrate is removed by again using anisotropical etching such as deep reactive ion etching (DRIE), and the silicon oxide mask is removed by wet etching with hydroﬂuoric acid. Lastly, through immersion in a 49 wt% potassium hydroxide aqueous solution for ten seconds to remove micro glass previously formed on a surface of the silicon wafer during the DRIE process, the mold M is obtained.

Next, an upper layer U of the channel unit 11 is prepared as illustrated in FIGS. 7(a) to 7(c).

For example, a face of the mold M may be subjected to hydrophobic treatment. The hydrophobic treatment may involve applying an FC coating on the surface as shown in FIG. 7(a), or silane treatment for making the surface hydrophobic without requiring an additional hydrophobic coating. For this, the silicon mold M is fixed to a petri dish using a Kapton tape. 98% ethoxytrimethylsilane is applied on the silicon mold M and the small petri dish, which are then maintained under vacuum in a vacuum chamber.

Subsequently by pouring a polymer (e.g. PDMS) over the mold M as shown in FIG. 7(b) and curing the same, an engraved structure transcribed from the embossed structure of the mold M is obtained. The engraved structure may or may not have a complete structure of the microﬂuidic channels 117.

When the engraved structure does not have the complete structure of the microﬂuidic charmels 117, holes are drilled from a surface opposite to the engraved surface as shown in FIG. 7(c) to form solution inlets 113, a solution outlet 115, or sensor insertion holes 119.

The holes laterally drilled fonn sensor insertion holes 119, whereas the hole drilled vertically forms a solution outlet 115.

Next, the previously formed upper layer U, bottom layer B, and ﬁber-optic localized surface plasmon resonance sensors 17 are assembled as illustrated in FIGS. 8(a) to 8(d).

As shown in FIG. 8(a), the engraved surface of the upper layer U is treated with oxygen plasma.

Subsequently, the ﬁber-optic localized surface plasmon resonance sensors are inserted into the grooves (or sensor holders) for forming the sensor insertion holes 113 as shown in FIG. 8(b). In this case, the ﬁber-optic localized surface plasmon resonance sensors 17 are positioned in such a way that front ends thereof are exposed to the microﬂuidic channels 117, to be speciﬁc, to the reaction chamber 118.

As illustrated in FIGS. 8(c) and 8(d), oxygen-plasma-treated slide glass (bottom layer B) is attached to the engraved surface of the upper layer U. Then, the slightly cured PDMS may be used as an adhesive that covers the optical ﬁber holder portion to prevent ﬂuid ﬂow.

[F iber-optic localized surface plasmon resonance sensor] FIG. 9 illustrates a ﬁber-optic localized surface plasmon resonance sensor applied to a surface plasmon resonance sensor device according to an example embodiment of the present invention. FIG. 10 (FIGS. l0(a) to 10(d)) illustrates a manufacturing process of a ﬁber- optic localized surface plasmon resonance sensor applied to a surface plasmon resonance sensor device according to an example embodiment of the present invention and also provides an image of the ﬁber-optic localized surface plasmon resonance sensor. FIG. 11 (FIGS. 11(a) and l1(b)) shows examples of a ﬁber-optic localized surface plasmon resonance sensor applied to a surface plasmon resonance sensor device according to an example embodiment of the present invention.

As illustrated in drawings, the sensors applied to the surface plasmon resonance sensor device according to example embodiments of the present invention are ﬁber-optic localized surface plasmon resonance sensors 17. Such sensors have a structure in which metal (e.g. gold or silver) nanoparticles 172 are adsorbed onto a core 171. 11, when excitation light is applied, the metal nanoparticles 172 resonate, thus reﬂecting light.

Then, a detector 52 measures the reﬂected light by receiving the same. The surface plasmon resonance sensor device according to example embodiments of the present invention may include a plurality of ﬁber-optic localized surface plasmon resonance sensors 17, and each of the sensors may include metal nanoparticles 172 on the core 171 thereof (FIG. 11(a)). In As shown in FIG. this case, the sensors may each have one of different metal nanoparticles of different resonance wavelengths. In addition, the antibodies bound to the metal nanoparticles of the ﬁber-optic localized surface plasmon resonance sensors 17 may be different for each sensor (FIG. ll(b)).

A multimode optical ﬁber having a core diameter of 105 um and a cladding diameter of 125 pm is used to prepare the ﬁber-optic localized surface plasmon resonance sensor 17 so that the sensor surface area is increased and light traveling through various paths can be received. In this way, a larger amount of light reﬂecting back to the sensor can be received during a measuring process. First, about 3 cm length of a jacket of the optical ﬁber is removed using an optical-ﬁber stripper, and an even sensor surface is prepared in a direction perpendicular to the path of light using an optical-ﬁber cutter.

As illustrated in FIG. 10, a three-step process for immobilizing metal nanoparticles on the evenly prepared optical-ﬁber surface is carried out to manufacture a fiber-optic localized surface plasmon resonance sensor.

As shown in FIG. 10(a), in the ﬁrst step, the optical fiber is immersed in a solution for minutes to remove organic substances and activate hydroxy groups. In this case, the solution is prepared by mixing sulfuric acid and hydrogen peroxide in a ratio of 4:1 (V/v). In the second step as illustrated in FIG. l0(b), the optical fiber is immersed in a 5% 3- (ethoxydimethylsilyl)-propylamine (APMES) solution for 90 minutes to prepare a self- assembled monolayer (SAM) for immobilizing gold nanoparticles on the optical-ﬁber surface, wherein each APMES molecule contains an ethoxy group on one end thereof to form a O-Si- O bond with the optical-ﬁber surface; and a positively charged amino group on the other end.

In the last step as illustrated in FIG. 10(c), the optical fiber is immersed in a gold colloid solution so that the positively charged amino group on one end of the SAM and negatively charged citrate surrounding the gold nanoparticles are bound to each other through electrostatic attraction, thus completing the manufacturing of an optical ﬁber localized surface plasmon resonance sensor. FIG. 10(d) shows metal (i.e. gold) nanoparticles 172 being bound to the core 171.

FIG. 12 shows an application example of sensor manufacturing based on a charmel unit applied to a surface plasmon resonance sensor device according to an example embodiment of the present invention.

As illustrated in the drawing, the channel unit according to example embodiments of the present invention can be integrated with a device capable of pretreating biomolecules, such as microﬂuidic devices and devices separating and concentrating particles, cells, and bacteria in conventional micro-TAS devices. The ﬁber-optic localized surface plasmon resonance sensors may also be implemented within the microﬂuidic channels, and used as a sensor platform that enables a user provided with the device to conduct all of optical-ﬁber surface treatment, sample pretreatment, measurement, and the like by using established experimental procedures.

[Surface plasmon resonance sensor system] FIG. 1 is a schematic view of a surface plasmon resonance sensor system according to an example embodiment of the present invention.

The surface plasmon resonance sensor system according to example embodiments of the present invention includes the above-described surface plasmon resonance sensor device 1, solution supply device 3, and optical measuring unit 5.

As described above, the surface plasmon resonance sensor device 1 includes a channel unit 11 and a plurality of ﬁber-optic localized surface plasmon resonance sensors 17.

The solution supply device 3 includes tubes 31 that are connected with the solution inlets 113 of the channel unit 11 on one end thereof; and a pump 32 that can be connected with the other end of the tubes 31. The pump 32 may be, for example, a syringe pump, and can be connected with the tubes 31 to inject solutions into the respective solution inlets 113 as in the example shown. Each of the tubes 31 is equipped with each of the shutoff valves 33 to prevent a solution from backﬂowing into tubes other than the tube being used for injecting the solution.

The optical measuring unit 5 includes a light source 51 and a detector 52. The light source 51 and the detector 52 are connected to a rear end of a 2:1 multimode ﬁber-optic localized surface plasmon resonance sensor 17 via an optical ﬁber coupler 53. Although the illustrated example shows only one optical measuring unit 5 for the convenience of understanding, one optical measuring unit 5 may be used for each of the plurality of surface plasmon resonance sensors 17.

The above surface plasmon resonance sensor system is capable of multi-sensing.

The light source 51 emits excitation light. A plurality of the light sources may be connected with a plurality of the optical ﬁber couplers 53 or one multi-branched optical ﬁber.

The detector 52 detects signals generated from the ﬁber-optic localized surface plasmon resonance sensors 17, and the number of the required detector(s) may be one or the same as the number of the optical ﬁber couplers 53. The optical ﬁber couplers 53 connect the ﬁber-optic localized surface plasmon resonance sensors 17 with the light sources 51 and the detectors 52 using an optical-ﬁber fusing machine or the like.

The light generated from the light sources 51 travels along the optical ﬁber couplers 53 and reaches ends of the ﬁber-optic localized surface plasmon resonance sensors 17, causes the gold nanoparticles on the sensor surface to generate localized surface plasmon resonance, reﬂects back, and is captured and measured by the detectors 52.

The device and system according to example embodiments of the present invention include: sensors having nanoparticles causing a localized surface plasmon resonance phenomenon; and antibodies bound to the nanoparticles, wherein the wavelengths at which the localized surface plasmon resonance phenomenon is generated and the antibodies bound to the nanoparticles are different for each sensor. Therefore, whenthe sensors are exposed to an inside of microﬂuidic channels, the device and system according to example embodiments of the present invention can detect changes in intensity and position of wavelengths that correspond to speciﬁc binding to an unknown antigen, and thus can identify a cause of a disease only with a single measurement. Since the amount of analytes is very small and identifying a disease requires various tests in the early stage of disease, the device and system according to example embodiments of the present invention are preferably applied to biosensors requiring high sensitivity and high throughput for diagnostic purposes.

Also by having an integrated structure of various sensors with mutually different localized surface plasmon resonance wavelengths and antibodies, the device and system according to example embodiments of the present invention can scan for diseases in multiple patients at once, and thus can be preferably applied to the ﬁeld of point-of-care (POC) diagnostics and early diagnosis.

While the example embodiments of the present invention and their advantages have been described in detail, it should be understood that various changes, substitutions and alterations may be made herein without departing from the scope of the invention.

[Description of Reference Numerals] 1: surface plasmon resonance sensor device 3: solution supply device : optical measuring unit(s) l 1: channel unit 17: ﬁber-optic localized surface plasmon resonance sensors 31: tubes 32: pump 33: shutoff valves 51: light source(s) 52: detector(s) 70: silicon substrate 71: embossed structured mask 1 13: solution inlets 17: microﬂuidic channel(s) 119: sensor insertion holes 172: metal nanoparticles B: bottom layer 72: embossed structure : solution out1et(s) 18: reaction chamber(s) 1 7 1 : core U: upper layer

Claims

WHAT IS CLAIMED IS:

1. A surface plasmon resonance sensor device comprising: a channel unit including: one or more microﬂuidic channels formed in a body thereof; and a plurality of sensor insertion holes, wherein each of the one or more microﬂuidic channels includes a plurality of solution inlets and one or more solution outlets, and the sensor insertion holes are formed from an outside and connected with the one or more microﬂuidic channels; and a plurality of ﬁber-optic localized surface plasmon resonance sensors, each of which is inserted into each of the plurality of sensor insertion holes.

2. The surface plasmon resonance sensor device of claim 1, wherein each of the plurality of ﬁber-optic localized surface plasmon resonance sensors includes metal nanoparticles on a surface of a core of a front end portion, wherein the front end portion is inserted into each of the plurality of sensor insertion holes.

3. The surface plasmon resonance sensor device of claim 1, wherein the channel unit includes a plurality of microﬂuidic channels in a body thereof, wherein the plurality of microﬂuidic channels are separate from one another and each of the plurality of microﬂuidic charmels includes a solution inlet and a solution outlet.

4. The surface plasmon resonance sensor device of claim 1, wherein the plurality of sensor insertion holes are formed laterally or vertically.

5. The surface plasmon resonance sensor device of claim 1, wherein each of the plurality of ﬁber-optic localized surface plasmon resonance sensors includes metal nanoparticles, and resonance wavelengths of the metal nanoparticles are different for each of the plurality of ﬁber-optic localized surface plasmon resonance sensors.

6. The surface plasmon resonance sensor device of claim 1 or 5, wherein each of the plurality of ﬁber-optic localized surface plasmon resonance sensors includes an antibody bound to the metal nanoparticles, and the antibody is different for each of the plurality of ﬁber-optic localized surface plasmon resonance sensors.

7. A surface plasmon resonance sensor system comprising: a channel unit including: one or more microﬂuidic channels formed in a body thereof; and a plurality of sensor insertion holes, wherein each of the one or more microﬂuidic channels includes x (X22) solution inlets and y (yzl) solution outlet(s), and the plurality of sensor insertion holes are connected with the one or more microﬂuidic channels from an outside; a plurality of ﬁber-optic localized surface plasmon resonance sensors, each of which is inserted into each of the plurality of sensor insertion holes and includes metal nanoparticles on a front end thereof; a solution injection unit connected with the solution inlets to enable an injection of each solution into each of the solution inlets; and one or more optical measuring units connected with the plurality of ﬁber-optic localized surface plasmon resonance sensors.

8. The surface plasmon resonance sensor system of claim 7, wherein each of the one or more optical measuring unit includes a light source and a detector connected with one of the ﬁber-optic localized surface plasmon resonance sensors corresponding to the optical measuring unit Via a multimode optical ﬁber coupler.

9. The surface plasmon resonance sensor system of claim 7, wherein the solution injection unit includes: tubes, each of which can be connected with each of the solution inlets from one end; and a pumping device for supplying test solutions from the other end, wherein each of the tubes is equipped with a shutoff valve capable of opening and closing the tube.

10. The surface plasmon resonance sensor system of claim 7, wherein each of the plurality of ﬁber-optic localized surface plasmon resonance sensors includes metal nanoparticles, and resonance wavelengths of the metal nanoparticles are different for each of the plurality of ﬁber-optic localized surface plasmon resonance sensors.

11. The surface plasmon resonance sensor system of claim 7, wherein each of the plurality of ﬁber-optic localized surface plasmon resonance sensors includes an antibody bound to metal nanoparticles, and the antibody is different for each of the plurality of ﬁber- optic localized surface plasmon resonance sensors.