Patent Publication Number: US-2018045667-A1

Title: Sensing apparatus

Description:
CROSS-REFERENCES 
     The present disclosure claims priority of Chinese Patent Application No. 201410385603.8 entitled “Sensing Apparatus” filed on Aug. 7, 2014, which is incorporated herein by reference in its entirety. 
     TECHNICAL FIELD 
     The disclosure generally relates to electrochemical detection, and more specifically, to a sensing device, such as an electrochemical biosensor. 
     BACKGROUND 
     An electrochemical biosensor comprises a biological sensitive element and an electrochemical sensor. The biological sensitive element comprises early enzyme catalyst electrode, and later DNA, antigen, antibody, animalcule, and animal and plant tissues. Performance of such sensors are continuously improved by various modern biological techniques and chemical modification techniques. 
     In conventional electrochemical sensors as illustrated in  FIG. 5 , detecting electrodes  506 - 1 ,  506 - 2  are generally fabricated on a silicon substrate or other substrates  502 . Probe molecules, indicated by Y-type symbols in the drawing, may be attached to electrodes  506 - 1 ,  506 - 2 . When fluid samples flow over the channel defined by the substrate  502  and the cover plate  504 , as indicated by the horizontal arrow in the drawing, a biochemical reaction may occur between the molecules to be detected in the samples (as indicated by the circle in the drawing) and the probe molecules. Variation of charges/currents during the biochemical reaction (generally, redox reaction) may be detected by the electrodes  506 - 1  and  506 - 2 . Typically, the electrode may have a structure of an Interdigitated microelectrodes Array (IDA). In such a case, two adjacent electrodes, which can be used as an oxidation electrode and a reduction electrode, respectively, constitute a group of electrode pair and may be applied with different bias voltages. The process may be cycled and reciprocated, and may be referred as redox cycling. As illustrated in  FIG. 5 , in a redox cycling, the reduction product (R) on the cathode  506 - 2  arrives at the anode  506 - 1  via diffusion and is oxidized. Then, the oxidation product (O) diffuses to the cathode and is reduced, and finally the cycling is completed. 
     In the redox cycling, the path along which the reaction products diffuse and the time for the diffusion depend on the distance between the cathode  506 - 2  and the anode  506 - 1 . The efficiency of the redox cycling can be improved by decreasing the spacing between adjacent electrodes, so as to increase the electrochemical detecting signals. Quantitatively, the steady-state current I limiting  in the redox cycling reaction can be derived by: 
     
       
         
           
             
               I 
               limiting 
             
             = 
             
               
                 nFC 
                 spe 
               
                
               
                 Dmb 
                  
                 
                   [ 
                   
                     
                       0.637 
                        
                       
                           
                       
                        
                       ln 
                        
                       
                         
                           2.55 
                            
                           
                             ( 
                             
                               w 
                               + 
                               g 
                             
                             ) 
                           
                         
                         g 
                       
                     
                     - 
                     
                       0.19 
                        
                       
                         
                           ( 
                           
                             g 
                             
                               w 
                               + 
                               g 
                             
                           
                           ) 
                         
                         2 
                       
                     
                   
                   ] 
                 
               
             
           
         
       
     
     wherein g is the spacing between the adjacent electrodes, w is the width of the electrode, m is the number of the Interdigitated electrode pairs, b is the length of the electrode, F is the Faraday constant, n is the number of the transferred electrons in the redox reaction, C spe  is the concentration of the redox molecules, and D is the diffusion coefficient of the redox molecules. According to the computation for the relationship between the steady-state current and the spacing of the interdigitated electrode pairs in a typical experimental condition, the steady-state current may decrease rapidly when the spacing is larger than several microns. 
     In order to make full use of the characteristics of the redox cycling and to increase the detecting current as large as possible, electrodes in micron or even nanometer scale are generally employed, and the spacing between electrodes are reduced as small as possible. In conventional methods, the spacing between electrodes in nanometer scale are fabricated by improving micro-nano fabricating process, for example, by deep ultraviolet lithography or electron beam lithography. However, the process difficulty and cost for fabricating nano-scale electrodes are increasing enormously with the scaling of the element. If electron beam lithography is employed, current nano-scale electrodes may have a dimension of about several nanometers, and long exposure time is required, which lead to lower yield. 
     Furthermore, in such an electrochemical detecting device, the molecules to be detected are transported in a flow-over mode, as illustrated in  FIG. 5 . Specifically, the molecules to be detected have to diffuse in the vicinity of the probe molecules in order to have a binding reaction. In a laminar flow state in micro-scale, binding efficiency of the molecules to be detected and the probe molecules is restricted. 
     SUMMARY OF INVENTION 
     An object of the present disclosure is to provide, among others, a sensing device, which can efficiently detect targeting particles, such as chemical and/or biological molecules. 
     According to embodiments of the present disclosure, a sensing device is provided. The sensing device comprises: a first electrode layer, a second electrode layer, which are separated by a dielectric layer; and through holes penetrating through the first electrode layer, the second electrode layer and the dielectric layer. 
     In the sensing device- according to embodiments of the present disclosure, spacings between electrodes in, for example, several to several tens of nanometers, are naturally formed by means of the dielectric layer between two electrode layers (which constitute a three-dimensional electrode configuration) without the complicated and expensive electron beam lithography process. 
     Furthermore, in conventional electrochemical sensors (as shown in  FIG. 5 ), molecules to be detected flow over the device (electrode). In a case where laminar-flow in micro-scale occurs, the reaction of molecules to be detected with probe molecules is mainly controlled by the diffusion speed of the molecules to be detected, which may lead to lower detecting speed and worse sensitivity. According to embodiments of the present disclosure, a novel micro/nano through hole structure is provided. Electrodes are disposed in different levels and fluid samples flow through the through holes, which greatly enhances diffusion efficiency of the molecules to be detected and probability with which the probe molecules react, and improves sensor sensitivity. 
    
    
     
       DESCRIPTION OF DRAWINGS 
       The above and other objects, features, and advantages of the present disclosure will become more apparent from the following descriptions of embodiments thereof with reference to attached drawings, in which: 
         FIG. 1  schematically illustrates a perspective view of a sensing device according to an embodiment of the present disclosure; 
         FIG. 2  schematically illustrates a cross-sectional view of a sensing device according to another embodiment of the present disclosure; 
         FIG. 3  schematically illustrates a cross-sectional view of a sensing device according to a further embodiment of the present disclosure; 
         FIG. 4  schematically illustrates a cross-sectional view of a sensing device according to a still further embodiment of the present disclosure; and 
         FIG. 5  illustrates a schematic view of an electrochemical sensor in related art. 
     
    
    
     DETAILED DESCRIPTION 
     Hereinafter, descriptions are given for embodiments of the present disclosure with reference to the attached drawings. However, it is to be understood that these descriptions are illustrative and not intended to limit the present disclosure. Further, in the following, known structures and technology are not described to avoid obscuring concepts of the present disclosure unnecessarily. 
     In the drawings, various structures according to embodiments of the present disclosure are schematically shown. However, they are not drawn to scale, and some features may be enlarged while some features may be omitted for sake of clarity. Moreover, shapes and relative sizes and positions of regions and layers shown in the drawings are only illustrative, and deviations may occur due to manufacture tolerances and technique limitations in practice. Those skilled in the art can also devise regions/layers of other different shapes, sizes, and relative positions as desired. 
     In the context of the present disclosure, when a layer/element is recited as being “on” a further layer/element, the layer/element can be disposed directly on the further layer/element, or otherwise there may be an intervening layer/element interposed therebetween. Further, if a layer/element is “on” a further layer/element in an orientation, then the layer/element can be “under” the further layer/element when the orientation is turned. 
     According to embodiments of the present disclosure, a sensing device is provided to detect targeting particles in samples, such as chemical and/or biological molecules. The sensing device comprises a first electrode layer, a second electrode layer, which are separated by a dielectric layer, and through holes penetrating through the first electrode layer, the second electrode layer and the dielectric layer. A through hole array may be formed in a cribriform structure. 
     The sandwich structure of the first and second electrode layers and the dielectric layer can be disposed on one side of a substrate, and the through holes may penetrate through the substrate. Optionally, a further sandwich structure of a further first electrode layer, a further second electrode layer and a further dielectric layer can also be disposed on the opposite side of the substrate. And the through holes may also penetrate through the further sandwich structure. 
     The through holes may have various types as appreciate (for example, for easy manufacturing), such as a substantially circular type. The through holes in the array may have the same or different types, and the respective through holes may have the same or different dimensions. The through holes may perpendicularly penetrate through the sandwich structure of the first electrode layer, the second electrode layer and the dielectric layer (and optionally, the substrate thereunder). Each through hole may have the same or different dimension in the first and second electrode layers. 
     According to embodiments of the present disclosure, the sensing device may comprise a microfluidic chip which is configured to introduce fluid samples into the device such that the samples can flow through the through holes. 
     Such sensing devices can be used as electrochemical biosensors. 
     The technology of the present disclosure can be implemented in various ways, some of which are exemplified in the following with reference to the drawings. 
       FIG. 1  schematically illustrates a perspective view of a sensing device according to an embodiment of the present disclosure. 
     As shown in  FIG. 1 , the sensing device  1000  according to the embodiment can comprise a substrate  1002 . For example, the substrate  1002  may comprise at least one of semiconductor materials, such as silicon, inorganic materials, such as glass and quartz, and polymers, such as polymethyl methacrylate and polycarbonate. 
     A first electrode layer  1004 , a dielectric layer  1006  and a second electrode layer  1008  are sequentially formed on the substrate  1002 . Optionally, a passivation layer  1010  may be formed on the second electrode layer  1008  to protect the respective layers thereunder. The respective layers can be formed on the substrate  1002  by, for example, deposition or evaporation. The first electrode layer  1004  and the second electrode layer  1008  may comprise appropriate conducting materials, for example, metals, such as Au, and may have a thickness of about several to hundreds of nanometers. In order to enhance adhesion between the electrode layer and the substrate  1002  or between the electrode layer and the dielectric layer  1006 , a transition layer may be formed between the electrode layer and the substrate  1002  and/or between the electrode layer and the dielectric layer  1006 . The transition layer may comprise conducting materials as appropriate, for example, metals, such as Ti, Cr, etc., and may have a thickness of about several to several tens of nanometers. The dielectric layer  1006  comprises dielectric materials as appropriate, for example, silicon oxide, silicon nitride, etc., and may have a thickness of about several to several tens of nanometers. The passivation layer  1008  may comprise silicon oxide, silicon nitride or other polymers, and may have a thickness of about several to hundreds of nanometers. 
     It should be noted that, the substrate beneath the sandwich structure of the electrode layers and the dielectric layer and the passivation layer on the sandwich structure are schematically shown in  FIG. 1 . However, they are optional. In some applications, the substrate and/or the passivation layer may be even omitted. 
     In the sandwich structure, through holes  1012  can be formed to penetrate through the sandwich structure on opposite sides (in the drawings, upper and lower sides) by, for example, an etching process. For example, the through holes  1012  may have a circular type and may have a diameter of about 100 nm-500 μm. In a case where the substrate  1002  and/or the passivation layer  1010  are formed, the through holes  1012  also penetrate through the substrate  1002  and/or the passivation layer  1010 . The fluid can flow through the through holes from one side of the device (for example, the upper side in  FIG. 1 ) to the other side (for example, the lower side in  FIG. 1 ), such that the fluid can flow through the first and second electrode layers, and electrochemical detecting is achieved with high efficiency. 
     Though an array of 4×4 through holes is shown in  FIG. 1 , the present disclosure is not limited thereto. There may be more or less through holes. Further, the array in  FIG. 1  is an array having a regular square shape. However, the present disclosure is not limited thereto. The through holes may be disposed in other regular or irregular patterns. The shapes of the through holes are not limited to the regular columniform shown in the drawings. The through holes may have any other shape which is suited for manufacturing, and may comprise variations in shape caused by manufacturing tolerance, process limitation, etc. 
     Further, in the example in  FIG. 1 , the sandwich structure of the electrode layers and the dielectric layer is only formed on one side (upper side in  FIG. 1 ) of the substrate  1002 . However, the present disclosure is not limited thereto. For example, another sandwich structure of the electrode layers and the dielectric layer can be formed on the opposite side (lower side in  FIG. 1 ) of the substrate  1002 . The electrode layers and the dielectric layer in the another sandwich structure may have the same or different configuration as that of the above sandwich structure. 
       FIG. 2  schematically illustrates a cross-sectional view of a sensing device according to another embodiment of the present disclosure. 
     As shown in  FIG. 2 , the sensing device  2000  according to the embodiment can comprise a substrate  2002 . A first electrode layer  2004 , a dielectric layer  2006 , a second electrode layer  2008  and a passivation layer  2010  are sequentially formed on the substrate  2002 . Description of the configuration of the substrate and these layers can be referred to explanation given with reference to  FIG. 1 . 
     The sensing device  2000  can also comprise a through hole ( 2012 - 1  and  2012 - 2 ) penetrating through the substrate  2002  and respective layers thereon. In the embodiment, the through hole has a dimension in the second electrode layer  2008  ( 2012 - 4 ) different (in this embodiment, larger) from that in the first electrode layer  2004  ( 2012 - 2 ). For example, such a through hole can be manufactured as follows. Specifically, the passivation layer  2010 , the second electrode layer  2008  and the dielectric layer  2006  are sequentially etched by, for example, Reactive Ion Etching (RIE) by means of a first photomask. The first photomask can define an opening with a relative large size. Next, the first electrode layer  2004  and the substrate  2002  are sequentially etched by means of a second photomask. The second photomask can define an opening with a relative small size. 
     The probe molecules, for example, antibody protein, as indicated by Y-type symbols in the drawings, can be attached to surfaces of the through holes exposed in the first electrode layer  2004  and the second electrode layer  2008 . Electrical signals, such as direct or alternating current signals, can be applied to the first electrode layer  2004  and the second electrode layer  2008 . Those skilled in the art can conceive various means to form connections such as wirings to apply electrical signals to the first electrode layer  2004  and the second electrode layer  2008 . When the fluid samples flow through the through hole along a direction indicated by the arrow in the drawing, the molecules to be detected in the samples (indicated by the circular symbol in the drawing) may react with the probe molecules, so as to achieve detection of the molecules to be detected. For particular molecules to be detected, it is apparent for selection of probe molecules for those skilled in the art. 
     It should be noted that only a single through hole ( 2012 - 1  and  2012 - 2 ) is shown in  FIG. 2  for the sake of convenience. However, the present disclosure is not limited thereto. There may exist more through holes. 
       FIG. 3  schematically illustrates a cross-sectional view of a sensing device according to a further embodiment of the present disclosure. The sensing device  3000  is substantially the same as the sensing device  2000  in  FIG. 2  except that the through holes have different shapes. 
     As shown in  FIG. 3 , the sensing device  3000  according to the embodiment can comprise a substrate  3002 . A first electrode layer  3004 , a dielectric layer  3006 , a second electrode layer  3008  and a passivation layer  3010  are sequentially formed on the substrate  3002 . Description of the configuration of the substrate and these layers can be referred to explanation given with reference to  FIG. 1 . 
     The sensing device  3000  can also comprise a through hole penetrating through the substrate  3002  and respective layers thereon. In the embodiment, the through hole have a dimension in the second electrode layer  3008  substantially the same as that in the first electrode layer  3004 . Specially, in the embodiment, the through hole has cross sections in substantially the same size to penetrate through the respective layers. For example, such a through hole can be manufactured as follows. Specifically, the passivation layer  3010 , the second electrode layer  3008 , the dielectric layer  3006 , the first electrode layer  3004  and the substrate  3002  are sequentially etched by, for example, Reactive Ion Etching (RIE) by means of the same photomask. 
     The probe molecules, for example, antibody protein, as indicated by Y-type symbols in the drawings, can be attached to surfaces of the through hole exposed in the first electrode layer  3004  and the second electrode layer  308 . Electrical signals, such as direct or alternating current signals, can be applied to the first electrode layer  3004  and the second electrode layer  3008 . When the fluid samples flow through the through hole along a direction indicated by the arrow in the drawing, the molecules to be detected in the samples (indicated by the circular symbol in the drawing) may react with the probe molecules, so as to achieve detection of molecules to be detected. 
       FIG. 4  schematically illustrates a cross-sectional view of a sensing device according to a still further embodiment of the present disclosure. 
     As shown in  FIG. 4 , the sensing device can comprise a substrate  4002 . A first electrode layer  4004 , a dielectric layer  4006 , a second electrode layer  4008  and a passivation layer  4010  are sequentially formed on the substrate  4002 . The sensing device can also comprise through holes penetrating through the substrate  4002  and respective layers thereon. Description of the configuration of the substrate and these layers can be referred to explanation given with reference to  FIGS. 1-3 . 
     The device can also comprise a microfluidic chip  4014 . The microfluidic chip  4014  can comprise an inlet  4016  for introducing fluid samples containing molecules to be detected into the device such that the fluid sample can flow through the through holes  4012 . Though only one inlet for sample loading is shown in  FIG. 4 , the present disclosure is not limited thereto. The microfluidic chip can comprise more inlets. 
     The microfluidic chip can precisely control and manipulate fluid in micro-scale. For example, the microfluidic chip may be manufactured of transparent polymers, such as Polymethylmethacrylate (PMMA), Polycarbonate (PC), Polydimethylsiloxane (PDMS), etc., and may have micro-structures, such as micro-channels, micro-cavities, etc., manufactured by microfabrication techniques. The micro-structures have at least one dimension in micro-scale among scales such as length, width, height, etc. A closed channel can be formed by bonding the microfluidic chip with structures thereunder or by applying pressure, so as to transport fluid. 
     Various features are described in different embodiments in the above descriptions. However, it is not implied that these features cannot be combined advantageously. 
     In the above, embodiments of the present disclosure are described. However, such embodiments are given for illustrative only, rather than limiting the scope of the present disclosure. The scope of the present disclosure is defined by appended claims and equivalents thereof. Without departing from the scope of the present disclosure, those skilled in the-art can make various alternations and modifications which fall within the scope of the present disclosure.