Patent Publication Number: US-2020300804-A1

Title: Sensor

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is based upon and claims the benefit of priority from Japanese Patent Application No. 2019-051716, filed Mar. 19, 2019, the entire contents of which are incorporated herein by reference. 
     FIELD 
     Embodiments described herein relate generally to a sensor. 
     BACKGROUND 
     There is a demand of improving the performance of sensors using a molecular identification function of a substance relating to a living body or an artificial matter. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a block diagram showing a sensor according to a first embodiment. 
         FIG. 2  is a plan view showing the sensor according to the first embodiment. 
         FIG. 3  is a cross section taken along III-III in  FIG. 2 . 
         FIG. 4  is a cross section taken along IV-IV in  FIG. 2 . 
         FIG. 5  is a diagram schematically showing an example of vesicle. 
         FIGS. 6A and 6B  are diagrams showing a method of adsorbing a vesicle on a graphene film in a trench. 
         FIG. 7  is a diagram illustrating a sensor according to a second embodiment. 
         FIG. 8  is a diagram illustrating a sensor according to a third embodiment. 
         FIGS. 9A and 9B  are diagrams illustrating a sensor according to a fourth embodiment. 
         FIGS. 10A, 10B and 10C  are diagrams illustrating a sensor according to a fifth embodiment. 
         FIG. 11  is a diagram illustrating a sensor according to a sixth embodiment. 
         FIGS. 12A and 12B  are diagrams illustrating a sensor according to a seventh embodiment. 
     
    
    
     DETAILED DESCRIPTION 
     In general, according to one embodiment, a sensor is disclosed. The sensor includes a predetermined number of vesicles and a first detector. The first detector includes a channel film that connects with the vesicles, and a trench provided for connecting the channel film with the vesicles. 
     Embodiments will be described hereinafter with reference to the accompanying drawings. The drawings are schematic or conceptual drawings, and dimensions and ratios are not necessarily the same as those in reality. Further, in the drawings, the same reference symbols (including those having different subscripts) denote the same or corresponding parts, and overlapping explanations thereof will be made as necessary. In addition, as used in the description and the appended claims, what is expressed by a singular form shall include the meaning of “more than one”. 
     First Embodiment 
       FIG. 1  is a block diagram schematically showing a sensor  1  which detects gas, according to the first embodiment. Here, the gas is made from, for example, odor molecules such as of alcohol or acetaldehyde. Note that the gas may as well be of odorless molecules. 
     The sensor  1  includes detectors  2  and a judging portion  3 .  FIG. 1  shows a plurality of detectors  2 , but the number of the detectors  2  may be one. Each of the detectors  2  outputs a detection signal S that indicates whether the gas is detected or not. When the detector  2  detects the gas, the detector  2  outputs a detection signal S that has a level of a predetermined value (threshold) or higher. When the detector  2  does not detect the gas, the detector  2  outputs a detection signal S that has a level lower than the threshold. 
     Note that, for simplicity,  FIG. 1  shows only four detectors. In practice, the number of detectors is, for example, about one million. The detectors (detector cells) are arranged, for example, two-dimensionally in a matrix. The present embodiment is explained on the assumption that each detector detects the same kind (molecular structure) of gas. 
     A plurality of detection signals S are input to the judging portion  3 . The judging portion  3  judges the number of gaseous molecules that are detection targets based on the signals S. For example, the judging portion  3  judges each of the detection signals input per unit time as to whether it has a level at the threshold or higher, and determines the total number of detection signals at a level of the threshold or higher, as the number of the gaseous molecules detected per unit time. 
     Detection signals obtained when the gas is detected can be easily discriminated from detection signals obtained when the gas is not detected by using, for example, a resistance measurement means (for example, Wheatstone bridge). For that reason, each of the detected levels can be easily and accurately judged as to whether it is at the threshold or higher. Thus, according to present embodiment, the sensor  1  with such an improved performance can be provided that the number of detected target gaseous molecules can be quantitatively obtained easily. 
     Note that, as described above, in  FIG. 1 , the number of the detectors  2  may be one, but if a plurality of detectors are employed as in present embodiment, the number of gaseous molecules can be quantitatively obtained easily. 
     Next, a concrete structure of the sensor  1  of present embodiment will be described. 
       FIG. 2  is a plan view showing the sensor  1  of present embodiment.  FIG. 3  is a cross section taken along III-III in  FIG. 2 , and  FIG. 4  is a cross section taken along IV-IV in  FIG. 2 . 
     As shown in  FIGS. 3 and 4 , the sensor  1  includes a substrate  10 , an insulating film  11  provided on the substrate  10 , and detectors  2  provided on the insulating film  11 . 
     The substrate  10  includes a semiconductor substrate. The semiconductor substrate is, for example, a silicon (Si) substrate or a silicon carbide (SiC) substrate. Note that, in place of the semiconductor substrate, a substrate containing a silicon oxide (for example, SiO 2 ), silicon nitride (for example, Si 3 N 4 ), or a polymeric material may be used. The insulating film  11  is, for example, a silicon oxide film. 
     The detectors  2  each contain a detecting element  5 . The detecting element  5  includes the insulating film  11 , a graphene film (channel film)  12 , a drain electrode  13 , a source electrode  14 , and a protective film  15 . 
     On the insulating film  11 , the graphene film (channel film)  12 , the drain electrode  13 , the source electrode  14 , and the protective film  15  are provided. The insulating film  11  is, for example, a silicon oxide film. 
     One end of each graphene film  12  is connected to the drain electrode  13 , the other end of the graphene film  12  is connected to the source electrode  14 , and the graphene film  12  connects the drain electrode  13  and the source electrode  14  to each other. The graphene film  12  contains a monolayer grapheme sheet or multi-layer graphene sheet. In place of the graphene film  12 , a silicon film or a carbon nanotube can be use as well. Moreover, a film containing the catalyst of graphene (catalyst film) may be provided between the insulating film  11  and the graphene film  12 . The catalyst film serves to facilitate the formation of the graphene film  12 . 
     The drain electrode  13  or the source electrode  14  is connected to the judging portion  3  shown in  FIG. 1 . The protective film  15  is formed on the graphene film  12 , the respective drain electrode  13  and the source electrode  14 . The protective film  15  includes a trench (groove)  16  which linearly exposes a part of an upper surface of the graphene film  12 . The dimension of trench  16  is set so that a predetermined number of vesicles can be adsorbed on the exposed surface of the protective film  15  by chemical bonding. The part of upper surface of graphene film  12  may be exposed into some other shape, for example, dot (rectangular). The protective film  15  is, for example, an insulating film such as a silicon nitride film. The protective film  15  protects the drain electrode  13  and the source electrode  14  from a measurement liquid. 
     A wall structure  17  enclosing the detecting elements  5  is provided on the protective film  15  such that the trench  16  is exposed. A material of the wall structure  17  is an insulator (for example, silicon oxide, silicon nitride, or polymeric material). The protective film  15  and the wall structure  17  form a well which reserves a measurement liquid in the trench  16 . The wall structure  17  define side walls of the well, and the protective film  15  defines a bottom surface of the well. In place of the well, a passage structure including a flow path may be used. 
     The substrate  10  includes a semiconductor substrate. The semiconductor substrate is, for example, a silicon (Si) substrate or a silicon carbide (SiC) substrate. Note that, in place of the semiconductor substrate, a substrate containing a silicon oxide (for example, SiO 2 ), a silicon nitride (for example, Si 3 N 4 ), or a polymeric material may be used. The insulating film  11  is provided on the substrate  10 . 
     The detecting element  5  is a field-effect type transistor (FET) element which includes the insulating film  11 , the graphene film (channel film)  12 , the drain electrode  13 , the source electrode  14  and the protective film  15 , and outputs a current (drain current). Note that, in place of the FET type element, a resistor element or a capacitor element can be used as well. The capacitor element includes, for example, micro-electromechanical systems (MEMS). 
     A measurement liquid (not shown) containing the gas is supplied into the well (or the flow path), and thus the measurement liquid is supplied in the trenches  16  of the detecting elements  5 . The measurement liquid contains a vesicle whose electrical characteristic such as an ion concentration changes when the gas adheres to the vesicle. 
       FIG. 5  is a diagram schematically showing an example of a vesicle  30 . 
     The vesicle  30  is an endoplasmic reticulum formed of a lipid bilayer and containing a liquid inside. In more detail, the vesicle  30  includes a spherical shell-like lipid structure  21  formed from of a phospholipid bilayer, an olfactory receptor (a first ion-channel receptor)  22  embedded in the lipid structure  21  and adsorbing gas, an olfactory receptor coreceptor (orco)  23  embedded in the lipid structure  21  and a liquid  24  contained in the lipid structure  21 . The olfactory receptor  22  and the orco  23  contain proteins and can migrate in the lipid structure  21 . 
     When the gas is adsorbed to the olfactory receptor  22 , the olfactory receptor  22  and the orco  23  migrate so as to form the first ion channel (now shown) which allows ions to pass into the lipid structure  21 . 
     When the ions flow into the lipid structure  21  through the first ion channel, the ion density on the graphene film  12  increases and the level of drain current (detection current) increases. The judging portion (not shown) can acquire the number of gaseous molecules quantitatively based on the level of the drain current (detection current) input from each detecting element. 
     As the volume (size) of the vesicle  30  is less, the degree of variation in the electric field in the surface of the vesicle  30 , associated with the variation in ion density  30  becomes higher. Therefore, as the volume (size) of the vesicle  30  is less, the variation in current can be detected with higher sensitivity. When the volume (size) of a vesicle is defined by its diameter, the value of the diameter is, for example, 50 nm or greater but 1 μm or less. 
     The trenches  16  shown in  FIGS. 3 and 4  have dimensions corresponding to the size of one vesicle. That is, one vesicle can enter one trench  16  on the graphene film  12  therein, but two or more vesicles cannot enter. 
       FIGS. 6A and 6B  are diagrams for illustrating a method of adsorbing a vesicle  30  on the graphene film  12  in the trench  16 . In this method, an olfactory receptor and an orco, which contain proteins that nonspecifically adsorb, are used. That is, a nonspecifically adsorbable vesicle is used. 
     As shown in  FIG. 6A , a liquid  6  having a high concentration of vesicles is dropped towards the trench  16 . As described above, the trench  16  has dimensions corresponding to the size of one vesicle  30 , one vesicle  30  is adsorbed by chemical bonding on the graphene film  12  in the trench  16 , as shown in  FIG. 6B . 
     In present embodiment, nonspecifically adsorbable vesicles  30  are used, and thus vesicles  30  may be located not only on the protective film  15  in the trench  16 , but also on the protective film  15  outside the trench  16 . However, such vesicles  30  located on the protective film  15  do not substantially affect the drain current, i.e., the gas detection accuracy. 
     Note that in place of the vesicle-containing measurement liquid, it is also possible to supply a measurement solution which does not contain vesicles, in the well in the state where one vesicle is adsorbed on the graphene film in the trench. That is, such a sensor may as well used, in which the vesicle  30  is preliminarily adsorbed on the graphene film in the trench. 
     In the following embodiments, for simplicity of explanation, types of sensors are not particularly distinguished as to whether vesicles are not adsorbed in advance on the graphene films in trenches or vesicles are adsorbed in advance. In the former case of sensors, a vesicle-containing measurement liquid is used. In the latter case of sensors, a measurement liquid which does not contain vesicles is used. 
     In the present embodiment, the graphene film  12  is used as a channel film, but a film comprising Si (silicon), Ge (gallium), group III-V element compound or C (carbon) may be used as a channel film. Furthermore, a film comprising substance that contains at least one of graphene, Si, Ge, group III-V element compound and C may be as a channel film. 
     Second Embodiment 
       FIG. 7  is a diagram illustrating a sensor according to the second embodiment. 
     Present embodiment is different from the first embodiment in that a vesicle  30   a  containing a developed lipid structure  21   a  is used. That is, in the first embodiment, as shown in  FIG. 5 , the lipid structure  21  has a spherical shell shape and the lipid structure  21  contains a liquid  24 , whereas in present embodiment, as shown in  FIG. 7 , the lipid structure  21  such a shape that a part of a spherical shell is cut out and the lipid structure  21  does not contain the liquid  24 . 
     The vesicle  30   a  is obtained by, for example, dropping a measurement liquid of a high vesicle concentration towards the trench  16  under a condition that the lipid structure should develop. 
     In present embodiment, ions flowing in from the ion channel are brought into contact with the graphene film  12  directly, and therefore the variation in ion density (drain current) can be detected at high sensitivity. 
     Third Embodiment 
       FIG. 8  is a diagram illustrating a sensor according to the third embodiment. 
     Present embodiment is different from the second embodiment in that a liquid (not shown) between the graphene film  12  (the first structure) and the vesicle  30   a  (the second structure) contains a first substance  41  and a second substance  42 . The second substance  42  is bonded to the graphene film  12 . 
     The first substance  41  selectively bonds to a predetermined ion which has passed through the first ion channel, that is, an ion that is detection target (first ion). The first ion is, for example, a calcium ion (Ca 2+ ). When the first ion is a calcium ion, the first substance  41  contains, for example, calmodulin. 
     The second substance  42  selectively bonds to a substance in which the first ion and the first substance  41  bond each other. When the first substance  41  is calmodulin, the second substance  42  contains, for example, calmodulin-dependent protein kinase. 
     Here, ions other than the first ion (ions which does not correspond to the gas of detection target) as well may pass the first ion channel. However, in present embodiment, with the first substance  41  and the second substance  42 , which have the above-described characteristics, the increase in the drain current (detection current) resulting from the first ion can be detected efficiently even when the ions other than the first ion may as well pass the first ion channel. In other words, the increase in the drain current (noise) resulting from the ions other than the first ion can be effectively suppressed. Therefore, according to present embodiment, the accuracy of detection gas can be improved. 
     Note that in  FIG. 8 , the second substance  42  is bonded to the graphene film  12 , but the second substance  42  may float in the liquid. Moreover, the first substance  41  and the second substance  42  may be bonded to the olfactory receptor  22 , or the first substance  41  and the second substance  42  may be bonded to the orco  23 . Further, the first substance  41  may be bonded to the olfactory receptor  22 , whereas the second substance  42  may be bonded to the orco  23 . Conversely, the first substance  41  may be bonded to the orco  23 , whereas the second substance  42  may be bonded to the olfactory receptor  22 . 
     Fourth Embodiment 
       FIGS. 9A and 9B  are diagrams illustrating a sensor according to the fourth embodiment. 
     In present embodiment, the case where a vesicle  30   b  which forms a first ion channel and a second ion channel is used. The vesicle  30   b  is developed. 
     Ion which passes the first ion channel (first ions) is different in kind from ion which passes the second ion channel (second ions). For example, the first ion and the second ion are a calcium ion and a potassium ion (K+), respectively. 
     The vesicle  30   b  contains a lipid structure  21   a , an olfactory receptor  22 , an olfactory receptor (a second ion channel receptor)  22   a , an orco  23  and an orco  23   a . When a gaseous molecule is adsorbed to the olfactory receptor  22 , the olfactory receptor  22  and orco  23  migrate so as to form the first ion channel which allows the first ion to pass through. In addition, when a gaseous molecule is adsorbed to the olfactory receptor  22   a , the olfactory receptor  22   a  and the orco  23   a  migrate so as to form the second ion channel which allows the second ion, which is different in kind from the first ion, to pass. 
     Each detector of present embodiment contains a detecting element  5  shown in  FIG. 9A  and a detecting element  5  shown in  FIG. 9B . The liquid between the graphene film  12  of the detecting element  5  shown in  FIG. 9A  and the developed vesicle  30   b  contains the first substance  41  and the second substance  42 . The liquid between the graphene film  12  of the detecting element  5  shown in  FIG. 9B  and the developed vesicle  30   b  contains the third substance  43  and the fourth substance  44 . The third substance  43  selectively bonds to the second ion having passed through the second ion channel. The fourth substance  44  selectively bonds to a substance in which the second ion and the third substance  43  bond each other. 
     With use of the first substance  41  to the fourth substance  44 , which have the above-described characteristics, the detecting element  5  of  FIG. 9A  selectively detects the first ion, and the detecting element  5  of  FIG. 9B  selectively detects the second ion. 
     Thus, even if a vesicle  30   b  which forms the first and second ion channels is used, the drain current resulting from the first ion and the drain current resulting from the second ion can be detected, respectively, at high sensitivity. Note that when using a vesicle which forms three or more ion channels, a technique similar to that described above can be used to detect drain current at high sensitivity. 
     Fifth Embodiment 
       FIGS. 10A to 10C  are diagrams illustrating a sensor according to the fifth embodiment. 
     In present embodiment, as shown in  FIG. 10A , a probe marker  25  is provided on a vesicle  30 . The probe marker  25  contains a substance which forms, for example, elements  21  to  24  (for example, protein, sugar chain, lipid). The probe marker  31  may be modified with molecules containing a substance different from the above-mentioned substance. 
     Further, as shown in  FIG. 10B , probes  26  are provided on a graphene film  12  in a trench  16 . The probes  26  specifically bond to the probe marker  25 . The material of the probe  26  contains an adapter such as a DNA that bonds to a specific protein, sugar chain, proteins such as an antibody, amino acid, or a compound. 
     When a liquid containing a vesicle  30  provided with the probe marker  31  is dropped towards the trench  16 , the probe  26  specifically bonds to the probe marker  25  as shown in  FIG. 10C . As a result, the graphene film  12  in the trench  16  is bonded to one vesicle  30  via the probes  26  and the probe marker  25 . The vesicle  30  is not bonded to the outside of the trench  16 . 
     Sixth Embodiment 
       FIG. 11  is a diagram illustrating a sensor according to the sixth embodiment. 
     In present embodiment, a vesicle  30   c  containing pure water  24   a  in its spherical shell-like lipid structure  21  is used. Further, a measurement liquid  40  containing a buffer solution is used. That is, in present embodiment, when the measurement liquid  40  is supplied, the difference in ion concentration between an inside and an outside of the vesicle  30   c  is adjusted to a certain degree or higher. The buffer solution contains, for example, Dulbecco&#39;s phosphate-buffered saline (DPBS). 
     By regulating the difference of the ion concentration to the certain degree or higher, the change of ion concentration in the vesicle  30   c  can be large, which is accompanied by opening and closing of the ion channel. Thereby, the variation in drain current (detection current) can be detected with high sensitivity. 
     Seventh Embodiment 
       FIGS. 12A and 12B  are diagrams illustrating a sensor according to the seventh embodiment. 
     In present embodiment, each detector contains a detecting element  5  shown in  FIG. 12A  and a detecting element  5 ′ shown in  FIG. 12B . A developed vesicle  30   d  which does not contain an olfactory receptor or orco is adsorbed on the graphene film  12  of the detecting element  5 ′. As the vesicle  30   d  does not form an on-channel, the number of ions in the vesicle  30   d  is substantially constant. 
     As a result, the ion density on the graphene film  12  of the detecting element  5 ′ is substantially constant, the level of the drain current of the detecting element  5 ′ is substantially constant. By using the drain current of the detecting element  5 ′ as a reference signal, the S/N ratio of detection current can be increased. For example, when the difference between the drain current of the detecting element  5 ′ and the drain current of the element structure  5   c  is used as a detection current, the S/N ratio of the detection current can be increased. 
     Note that, the S/N ratio of the detection signal can be also improved by using a vesicle embedded with a compound through which the ions of the detection targets continue to selectively pass, instead of using the vesicle  30 . The compound is, for example, a low-molecular compound such as an ionophore. 
     Note that, in the first to seventh embodiments, chemical interactions are utilized to adsorb one vesicle on the graphene film in the trench, but electric interactions (for example, electrostatic interaction) may be utilized as well. 
     Moreover, in the first to seventh embodiments, the vesicle (endoplasmic reticulum) that can open and close the ion channel is used, but in place, a cell that can open and close the ion channel may be used as well. Alternatively, a part of the above mentioned vesicle (endoplasmic reticulum) or a part of the above mentioned cell may be used as well. 
     Moreover, in the first to seventh embodiments, the odor is detected based on the variation in the ion concentration on the graphene film (the variation in electrical characteristic) accompanied by opening and closing of the ion channel, but the odor may be detected based on variation in the size or shape of vesicle (structural variation) or a structural variation of a member bonded to the vesicle. 
     Furthermore, the first to seventh embodiments are related to the sensor that detects odor as a detection target, but the embodiments are applicable to a sensor that detect other detection target, for example, gustatory. 
     While certain embodiments have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Indeed, the novel embodiments described herein may be embodied in a variety of other forms; furthermore, various omissions, substitutions and changes in the form of the embodiments described herein may be made without departing from the spirit of the inventions. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the inventions.