Ion-sensitive field effect transistor and extended field effect bio-detection chip
By employing a three-dimensional conductive structure and conductive nanoparticles to form an undulating surface in a semiconductor biosensor, the problems of high hardware cost and decreased sensitivity in existing technologies are solved, achieving more efficient detection of biomaterials.
Patent Information
- Application Number
- CN202410329427.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2023-09-28
- Filing Date
- 2024-03-21
- Publication Date
- 2025-11-07
- Estimated Expiration
- 2044-03-21
AI Technical Summary
Existing semiconductor biosensors suffer from high hardware costs, decreased sensitivity, and poor flexibility when detecting various biological materials. In particular, the capacitance between the floating gate and the substrate of extended gate field-effect transistors causes severe signal attenuation.
The device employs a three-dimensional conductive structure, including multiple conductive structures perpendicular and parallel to the substrate surface, to increase the reaction area with the biomaterial to be detected. It also uses conductive nanoparticles to form an undulating surface to enhance sensitivity, and uses staggered detection electrodes to improve detection efficiency.
It achieves a larger reaction area and sensitivity, reduces hardware costs, improves detection flexibility and signal-to-noise ratio, and reduces signal attenuation.
Smart Images

Figure CN118032901B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to hardware using transistors to detect biological samples, in particular, to ion-sensitive field effect transistors and extended field effect biological detection chips that can increase the reaction area to improve the efficiency and flexibility of the reaction and handle a plurality of biological samples to be detected. BACKGROUND
[0002] One of the important issues in the biomedical field is early diagnosis and health monitoring, and the goal is to detect disease information as early as possible and treat it as early as possible. Since biological materials such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA), protein, cell, biological tissue, microorganism, enzyme, antibody, and antigen carry specific biological information, by detecting these biological materials, the biological information related to the pathogen, physiological activity, or even enzyme kinetics can be determined.
[0003] Biosensors are important tools for detecting biological information, and they have high sensitivity, fast response, and high efficiency. They play an important role in the fields of healthcare, environmental protection, and food safety. Generally, a biosensor consists of two parts: a biological detection film and a transducer. The biological detection film reacts with the biological material to be detected, and the transducer converts the information generated by the biological material to be detected into an electrical signal that can be provided to external hardware such as integrated circuits.
[0004] Generally, the existing semiconductor biosensor architecture can be divided into two categories. One is to directly integrate the transducer (or transistor) and even the biological detection film on the substrate, and the other is to separate the transducer (or transistor) and the biological detection film. The former has the advantages of easy design, easy manufacturing, and easy use, but the disadvantage is that if there is a problem that needs to be repaired or different biological materials need to be detected, the entire device needs to be replaced, resulting in high cost and waste. The latter has the advantages of not directly reacting the transistor and the biological material, which can reduce the design difficulty, easy to manufacture and reduce pollution, but the disadvantage is that if multiple biological materials need to be detected in sequence, the hardware needs to be set up for each biological material, which increases the cost of hardware and reduces the flexibility of use.
[0005] In recent years, semiconductor biosensors have gradually become popular by using the semiconductor technology that has been commercialized, especially the field-effect transistor (FET) that has many mature designs that can be directly referenced. The basic architecture of the semiconductor biosensor is formed by a semiconductor component that provides a converter function and a biomolecular recognition component that provides a biological detection film function. For example, the ion-sensitive field-effect transistor (ISFET) developed since the early 1970s converts the chemical and / or biological reaction of the reaction film into an electrical signal through the transistor.
[0006] Further, with the development of complementary metal-oxide-semiconductor (CMOS) technology, the gate of the ion-sensitive field-effect transistor can be connected to a metal reaction plate (or floating gate) above and separated from the substrate by one or more metal interconnects or vias. The dielectric layer covering the floating gate (or even the floating gate itself) can act as a sensing layer that binds to the charged target. When the biological material to be detected is applied to the substrate (or to the ion-sensitive field-effect transistor), the binding process with the biological material to be detected changes the potential of the sensing layer facing the biological material to be detected, thereby changing the on-off state of the transistor, so that the condition of the biological material to be detected can be reflected in the electrical signal passing through the transistor. The extended-gate field-effect transistor (EGFET) with the above-mentioned architecture has advantages in long-term stability, light insensitivity, noise reduction, and feasibility of optimizing the sensing pixel size and transistor geometry. However, the extended-gate field-effect transistor with the above-mentioned architecture still has some disadvantages. For example, due to the capacitance between the floating gate and the substrate and / or the surrounding dielectric, or even the capacitance between the biological material to be detected and the substrate, etc., only a part of the signal from the sensing layer can be coupled to the floating gate, and the extended-gate field-effect transistor cannot correctly and / or in real time measure the biological material to be detected, resulting in significant signal attenuation and sensitivity reduction. Although increasing the size of the entire extended-gate field-effect transistor, such as increasing the size of the floating gate or adjusting the thickness from the surface of the substrate to the floating gate, can reduce these capacitance values. However, this inevitably increases the material cost and is not conducive to forming a compact extended-gate field-effect transistor array. In particular, as the sensing layer thickness decreases to approach the physical limit, more significant signal attenuation will occur.
[0007] Therefore, there is still a need to continuously improve the biosensor using the semiconductor technology, so as to more efficiently, accurately and cost-effectively detect biological materials. SUMMARY
[0008] The present invention provides an ion-sensitive field effect transistor, which comprises a substrate, a gate, a source, a drain, a floating gate, a first conductive structure and at least two second conductive structures. The gate is located on the substrate, and the source and the drain are both located on the substrate and are respectively located on the two sides of the gate. The first conductive structure extends along a direction perpendicular to the surface of the substrate and one end of the first conductive structure is connected to the gate. The floating gate is located above the substrate and is separated from the substrate, and the other end of the first conductive structure is connected to the floating gate. Any second conductive structure is separated from the substrate and other second conductive structures, and is connected to the first conductive structure or the floating gate. The first conductive structure is connected by at least one metal interconnection. The floating gate is formed by a certain conductor material. Obviously, compared with the prior art in which only a metal interconnection is used to connect the transistor gate located on the substrate and the floating gate located above the substrate, the main feature of the ion-sensitive field effect transistor provided by the present invention is that the second conductive structures are staggered with the metal interconnection and separated from the substrate, or in other words, in addition to the series of metal interconnections connecting the floating gate and the gate, there are multiple conductive structures perpendicular to the surface of the substrate or parallel to the surface of the substrate, whether these conductive structures are located between the floating gate and the gate (and the substrate) or above the floating gate. Obviously, the presence of the second conductive structures can increase the area that can react with the biological material to be detected.
[0009] Optionally, at least one first additional conductive structure is further included. Any first additional conductive structure is separated from the substrate, the floating gate, the first conductive structure and other first additional conductive structures. Any first additional conductive structure has one end connected to a certain second conductive structure and extends along a direction perpendicular to the surface of the substrate. That is, the profile of the conductive structures between the substrate and the floating gate can have more changes, especially more branches perpendicular to the surface of the substrate, thereby increasing the area that can react with the biological material to be detected.
[0010] Optionally, at least one second additional conductive structure is further included. Any second additional conductive structure is separated from the substrate, the floating gate, the first conductive structure, the second conductive structures and other second additional conductive structures. Any second additional conductive structure has one end connected to a certain first additional conductive structure and extends along a direction parallel to the surface of the substrate. That is, the profile of the conductive structures between the substrate and the floating gate can have more changes, especially more branches perpendicular to the surface of the substrate and more branches parallel to the surface of the substrate, thereby further increasing the area that can react with the biological material to be detected.
[0011] Optionally, at least one second additional conductive structure is also included, each of the at least one second additional conductive structure extending along a direction parallel to the surface of the substrate, each of the at least one second additional conductive structure being separated from the substrate, the floating gate, and the other second additional conductive structures;
[0012] In which, each of the at least one second additional conductive structure is connected to a corresponding second conductive structure. That is, the profile of the conductive structures between the substrate and the floating gate can be made to have more undulations, especially more branches perpendicular to the surface of the substrate and more branches parallel to the surface of the substrate, so as to further increase the area that can react with the biological material to be detected.
[0013] Optionally, at least to protect the conductive structures, or even to adjust the interaction between the conductive structures and the biological material to be detected (for example, to adjust the electrical properties between them), a dielectric layer can also be included between the conductive structures and the biological material to be detected. For example, a dielectric layer on the substrate and covering the first conductive structures, the floating gate, and all the second conductive structures, or a dielectric layer on the substrate and conformally distributed on the surfaces of the first conductive structures, the floating gate, all the second conductive structures, and all the first additional conductive structures, or a dielectric layer on the substrate and conformally distributed on the surfaces of the first conductive structures, the floating gate, all the second conductive structures, all the first additional conductive structures, and all the second additional conductive structures.
[0014] Optionally, the material of the dielectric layer is typically or generally silicon dioxide (SiO2) commonly used to protect semiconductor structures, or titanium nitride (TiN) that can reduce the capacitance value.
[0015] Optionally, since the main difference with respect to the prior art is the profile of the conductive structures between the substrate (or transistor) and the biological material to be detected, the material of the conductive structures can have many variations. For example, the material of the floating gate, the first conductive structures, any of the second conductive structures, any of the first additional conductive structures, or any of the second additional conductive structures can be aluminum, copper, silver, gold, and any combination thereof, or even other metals or conductive materials.
[0016] Alternatively, to increase the reaction area with the material to be detected, a plurality of conductive nano-particles can also be used to increase the surface area of at least one of the conductive structures, such as forming a plurality of conductive nano-particles on at least one surface of the floating gate, the first conductive structure, any of the second conductive structures, any of the first additional conductive structures, and / or any of the second additional conductive structures, to form a three-dimensional surface to improve the sensitivity to surface charge changes. Of course, in some variations, the second conductive structures, the first additional conductive structures, and / or the second additional conductive structures are formed of a plurality of conductive nano-particles. Generally, to simplify the structure and the corresponding manufacturing process, the conductive nano-particles and the conductive structure on which the conductive nano-particles are located are made of the same material, but the present application does not need to be so limited, as long as the conductive nano-particles can be secured on the conductive structure, and as long as both the conductive nano-particles and the conductive structure can transmit electrical signals and there is no significant noise between them. For example, the plurality of conductive nano-particles can be located on the upper surface of the floating gate, or the plurality of conductive nano-particles can be located on at least one surface of the floating gate, or the plurality of conductive nano-particles can be located on the upper surface of the uppermost one of the second conductive structures, or the plurality of conductive nano-particles can be located on at least one surface of the uppermost one of the second conductive structures, or the plurality of conductive nano-particles can be located on the upper surface of at least one of the second conductive structures, or the plurality of conductive nano-particles can be located on at least one surface of at least one of the second conductive structures, or the plurality of conductive nano-particles can be located on the upper surface of the uppermost one of the first additional conductive structures, or the plurality of conductive nano-particles can be located on at least one surface of the uppermost one of the first additional conductive structures, or the plurality of conductive nano-particles can be located on the upper surface of at least one of the first additional conductive structures, or the plurality of conductive nano-particles can be located on at least one surface of at least one of the first additional conductive structures, or the plurality of conductive nano-particles can be located on the upper surface of the uppermost one of the second additional conductive structures, or the plurality of conductive nano-particles can be located on at least one surface of the uppermost one of the second additional conductive structures, or the plurality of conductive nano-particles can be located on the upper surface of at least one of the second additional conductive structures, or the plurality of conductive nano-particles can be located on at least one surface of at least one of the second additional conductive structures.
[0017] The present application also provides an extended field effect bio-detection chip. It comprises a substrate, a dielectric layer, a conductive transmission layer, a conductive detection layer and a signal output component. The dielectric layer is on the substrate, the conductive transmission layer is surrounded by the dielectric layer, and the conductive detection layer is on the conductive transmission layer and surrounded by the dielectric layer. In addition, one end of the signal output component is on the part of the substrate surrounded by the dielectric layer, and the other end is separated from the substrate, the dielectric layer, the conductive transmission layer and the conductive detection layer. Thus, when the biological probe used to react with the biological material is electrically connected to the conductive detection layer, the reaction with the biological material can be converted into the corresponding electrical signal and transmitted to the external integrated circuit or even microprocessor, mobile phone, laptop, host and other hardware that can process electrical signals and analyze the biological information represented by them. Even, by properly arranging the conductive transmission layer, the conductive detection layer and the signal output component, multiple same or different biological probes can be connected to the external hardware, thereby detecting multiple same or different biological materials to be detected.
[0018] Alternatively, one end of the signal output component can be connected to the conductive transmission layer or the conductive detection layer. The key point is that the electrical signal can be transmitted from the connected biological probe to the connected external hardware (integrated circuit, etc.) together with the signal output component.
[0019] Alternatively, the conductive detection layer is composed of multiple detection electrodes, which are arranged in multiple groups and spaced apart from each other between adjacent two groups of detection electrodes. The group-arranged detection electrodes can be connected to different biological probes, respectively.
[0020] Alternatively, the lower surface of any detection electrode is connected to the conductive transmission layer, and the upper surface of any detection electrode protrudes above the upper surface of the dielectric layer. That is, the upper surface of the detection electrode is used to connect to the biological probe, and the lower surface of the detection electrode is used to connect to the signal output component.
[0021] Alternatively, the conductive transmission layer comprises multiple conductive connection paths, so that the lower surface of different detection electrodes is connected to different conductive connection paths, and the part of the surface of different detection electrodes protruding above the upper surface of the dielectric layer is connected to different biological probes, respectively. That is, it is a way to connect multiple same or different biological probes to the external hardware (integrated circuit, etc.) that can process electrical signals, respectively.
[0022] Alternatively, at least one detection electrode has a surface modification layer on its upper surface to facilitate the binding of the corresponding biological probe. Since the surface modification layer used to make the detection electrode and the biological probe more easily bind is known technology, the details can be omitted.
[0023] Alternatively, in some embodiments, the distance between the plurality of detection electrodes in the same group is between 30 μm and 150 μm, and the distance between the different groups of detection electrodes is between 300 μm and 500 μm. Of course, in different embodiments, the respective distances can be different, depending on the size of the biological probes used, the profile of the biological probes used, the dielectric properties of the dielectric layer material used, and so on.
[0024] Alternatively, the profile of any of the detection electrodes comprises a connecting section and a protruding section, wherein the connecting section is located in the dielectric layer and its lower surface is in contact with the conductive layer, and the protruding section protrudes out of the dielectric layer. That is, different parts of the detection electrodes serve different purposes. The connecting section, which is located in the dielectric layer, is used to connect to the conductive layer, and the protruding section, which is located above the dielectric layer, can be used to contact the biological probes.
[0025] Alternatively, the dielectric layer comprises a first dielectric layer and a second dielectric layer. The first dielectric layer is located on the substrate, and the conductive layer is located on the first dielectric layer. The second dielectric layer is located on the first dielectric layer and surrounds the conductive layer. The second dielectric layer has a plurality of through-slots (or holes) that are connected to the conductive layer, and the connecting sections of the detection electrodes pass through the through-slots to contact the conductive layer, but the protruding sections of the detection electrodes are located above the second dielectric layer (or above the through-slots, respectively).
[0026] Alternatively, in different embodiments, at least one of the protruding sections has a polygonal cross-sectional shape, at least one of the protruding sections has a circular cross-sectional shape, at least one of the protruding sections has a tapered profile that is narrower at the top and wider at the bottom, at least one of the protruding sections has a cylindrical profile, at least one of the protruding sections has a truncated-cone profile, or at least one of the protruding sections has a conical profile. That is, the protruding sections are designed to ensure that they can contact the biological probes. Depending on the design of the biological probes, or even depending on the biological materials to be detected and the specific configuration of the entire extended field-effect bio-detection chip, the profiles of the protruding sections can vary.
[0027] Alternatively, in some embodiments, the ratio between the height of at least one of the protruding sections and the diameter of the upper surface of the protruding section is at least ten. Because the protruding sections are designed to ensure that they can contact the biological probes, if the ratio of the height to the width is too low, it can have a negative impact. Of course, in different embodiments, the lower limit of the ratio of the height to the width can be different.
[0028] Optionally, the detection electrodes further comprise an extension section, wherein the extension section is located above the protruding sections and connects the protruding sections together. That is, more channels for electrical signal transmission are provided.
[0029] Optionally, the plurality of reference electrodes are further connected to the conductive layer. That is, the reference electrodes are used to provide a reference potential, and it does not matter whether the reference potential is introduced through the conductive layer or the conductive sensing layer.
[0030] Optionally, the conductive sensing layer comprises a plurality of first detection electrodes, wherein a lower surface of each of the first detection electrodes is connected to the conductive layer and an upper surface of each of the first detection electrodes is located below an upper surface of the dielectric layer, a recess is formed between the upper surface of each of the first detection electrodes and the upper surface of the dielectric layer, and each of the first detection electrodes is connected to a lower surface of a reference electrode, wherein an upper surface of the reference electrode is higher than the upper surface of the dielectric layer. That is, in order to connect to a plurality of biological probes, the conductive sensing layer can not only be a combination of a plurality of first detection electrodes, but each of the first detection electrodes can have a special geometric shape and a special connection relationship with adjacent structures.
[0031] Optionally, the conductive sensing layer further comprises a plurality of second detection electrodes in addition to the plurality of first detection electrodes, wherein a lower surface of each of the second detection electrodes is connected to the conductive layer and an upper surface of each of the second detection electrodes is located above the upper surface of the dielectric layer. That is, for different biological probes, or for different biological materials to be detected, there can be different types of detection electrodes or detection electrodes connected to different signal output components (or different external integrated circuits, etc.), but the configurations of the various detection electrodes can be similar or different.
[0032] Optionally, a plurality of biological probes are connected to the upper surfaces of the first detection electrodes through the recesses, respectively, or a plurality of biological probes are connected to the portions of the second detection electrodes protruding above the upper surface of the dielectric layer, respectively. That is, for different biological probes, or for different biological materials to be detected, there can be different types of detection electrodes or detection electrodes connected to different signal output components (or different external integrated circuits, etc.), but the configurations of the various detection electrodes can be similar or different.
[0033] Alternatively, the first detection electrodes and the second detection electrodes are arranged in groups, and each group of the first detection electrodes and each group of the second detection electrodes are staggered. That is, in addition to arranging different types of detection electrodes in different geometric positions relative to the conductive layer, and staggering different types of detection electrodes to make full use of the space on the conductive layer, thereby reducing the size of the entire extended field effect bio-detection chip.
[0034] Alternatively, each group of the first detection electrodes is connected to a plurality of biological probes, and the conductive layer includes a plurality of first conductive connection paths, wherein each of the first conductive connection paths is connected to a biological probe. Also alternatively, each group of the second detection electrodes is connected to a plurality of biological probes, and the conductive layer includes a plurality of second conductive connection paths, wherein each of the second conductive connection paths is connected to a biological probe. That is, the first detection electrodes and the second detection electrodes can be respectively connected to a plurality of signal output components via a plurality of conductive connection paths, thereby connecting to a plurality of integrated circuits or other hardware outside for processing electrical signals.
[0035] Alternatively, in some embodiments, the depth of each recess is between 1 μm and 5 μm, or the distance between each first detection electrode in the same group is between 30 μm and 150 μm (i.e., the distance between two adjacent first detection electrodes in the same group is between 30 μm and 150 μm), or the distance between each second detection electrode in the same group is between 30 μm and 150 μm (i.e., the distance between two adjacent second detection electrodes in the same group is between 30 μm and 150 μm), or the distance between the first detection electrode and the second detection electrode of adjacent groups is between 300 μm and 500 μm (i.e., the distance between an adjacent first detection electrode and an adjacent second detection electrode of adjacent groups is between 300 μm and 500 μm). Of course, in different embodiments, these items can have different data values depending on the selection of various related parameters.
[0036] Alternatively, the profile of each second detection electrode includes a connection section and a protruding section, wherein the connection section is located in the dielectric layer and its lower surface is in contact with the conductive layer, and the protruding section protrudes from the dielectric layer. That is, different parts of the second detection electrode have different functions, the connection section inside the dielectric layer is used to connect to the conductive layer, and the protruding section above the dielectric layer can be used to contact the biological probe.
[0037] Alternatively, in different embodiments, the cross-sectional shape of the at least one protrusion is polygonal, or the cross-sectional shape of the at least one protrusion is circular, or the profile of the at least one protrusion is tapered, or the profile of the at least one protrusion is cylindrical, or the profile of the at least one protrusion is frustoconical, or the profile of the at least one protrusion is conical. That is, the protrusion is designed to be connected to the biological probe, and depending on the design of the biological probe, or even depending on the biological material to be detected and the overall configuration of the field-effect biosensor chip, the profile of the protrusion can vary. Of course, the second detection electrode and the first detection electrode can have different designs of connecting segments and protrusions.
[0038] Alternatively, in some embodiments, the ratio of the height of the at least one protrusion to the diameter of the upper surface of the at least one protrusion is at least ten. Because the protrusion is designed to be connected to the biological probe, if the ratio of the height to the diameter is too low, it can have a negative effect. Of course, different second detection electrodes and different first detection electrodes can have different ratios of the height to the diameter of the protrusion. Because not only the geometry of the first detection electrode and the second detection electrode is different, but also they can be connected to different biological probes.
[0039] Alternatively, the detection electrodes further comprise an extension segment, wherein the extension segment is located above the protrusions and connects the protrusions together. That is, more channels for the transmission of electrical signals are provided. The plurality of first detection electrodes and the plurality of second detection electrodes each have more channels for the transmission of electrical signals.
[0040] Alternatively, in order to further enhance the binding to the biological probe, in order to further facilitate the transmission of the signals resulting from the reaction with the biological material, a surface modification layer facilitating the binding of the corresponding biological probe can be present on the upper surface of the at least one first detection electrode, or a surface modification layer facilitating the binding of the corresponding biological probe can be present on the upper surface of the at least one second detection electrode.
[0041] Optionally, in some embodiments, the dielectric layer comprises a first dielectric layer, a second dielectric layer and a third dielectric layer. The first dielectric layer is disposed on the substrate, the conductive layer is disposed on the first dielectric layer, and the second dielectric layer is disposed on the first dielectric layer and surrounds the conductive layer. The second dielectric layer has a plurality of first communication slots respectively connected to the conductive layer, and the connecting segments of the first detection electrodes and the connecting segments of the second detection electrodes respectively pass through the first communication slots to contact the conductive layer. The third dielectric layer is disposed on the second dielectric layer and surrounds the conductive layer, and the third dielectric layer has a recess above each of the first detection electrodes. The third dielectric layer has a plurality of second communication slots above each of the second detection electrodes, one end of the protruding segments of the second detection electrodes respectively passes through the second communication slots to contact the connecting segments, and the other end of the second detection electrodes respectively protrudes above the third dielectric layer. Of course, this is only one embodiment, and the present application can have other structural changes.
[0042] Additionally, it is common practice to dissolve or gel the biological material to be detected into a solution or gel, and then allow it to react with the floating gate or sensing electrode, etc. Therefore, the signal strength of the electrical signal related to the type and amount of biological material to be detected is often not large, especially compared to the electrical signal used in general memory and microprocessors, etc. Both the current and voltage values are significantly smaller. Therefore, in order to strengthen the detection of the electrical signal related to the biological material to be detected, the gate channel of the transistor used to react with the biological material to be detected can be adjusted to the linear region (or active region) before detection. In this way, the transistor can provide an amplifier-like function to amplify the electrical signal related to the biological material to be detected before outputting it to the integrated circuit, processor or application program for further processing. One specific implementation is to use the known back gate technology and back gate bias effect, for example, refer to Deepa Bhatt and Siddhartha Panda's article titled "Dual-gate ion-sensitive field-effect transistors: A review" published on December 16, 2021 in Chemistry Europe, network link https: / / chemistry-europe.onlinelibrary.wiley.com / doi / full / 10.1002 / elsa.202100195. Figure 2 of this paper, especially its second D figure, shows that an electrode is formed on the side of the transistor used to react with the biological material to be detected, which is opposite to the biological material to be detected, as a back gate. Then the voltage applied to the back gate can be adjusted to adjust the operation of the transistor for sensing the biological material to be detected. Therefore, by applying this concept, all embodiments and related variations of the present application can first form an electrode inside the substrate and connect it to a power source to form a back gate, and then form a transistor for reacting with the biological material to be detected and other related structures on the substrate. For example, first form a back gate inside the substrate and a transistor for reacting with the biological material to be detected on the surface of the substrate, and then sequentially form a floating gate above the transistor for reacting with the biological material to be detected, etc. In this way, the back gate can be used to adjust the transistor for reacting with the biological material to be detected to the linear region (or active region), so as to amplify the detected electrical signal related to the biological material to be detected, and then output the amplified electrical signal to the outside for further analysis and processing.That is, various embodiments and related variations of the present application can more sensitively detect the presence of electrical signals associated with the biological material to be detected, the signal size and changes thereof, and the like.
[0043] The ion-sensitive field effect transistor provided by the present application has at least the following beneficial effects. First, it can be formed using commercial semiconductor processes, whether metal interconnection processes or stacked metal layers and dielectric layers or others, without process difficulties. Second, the three-dimensional conductive structure composed of one or more conductive structures perpendicular to the substrate surface and one or more conductive structures parallel to the substrate surface can increase the reaction area with the biological material to be detected on the one hand and does not occupy more substrate area than the prior art on the other hand. In this way, a more compact biosensor can be formed, and signal attenuation and sensitivity reduction caused by various capacitances can be effectively reduced. In particular, the thickness of the sensing layer (or floating gate) can be reduced to a state close to the physical limit compared to the prior art. Furthermore, by using conductor nanoparticles to give the entire three-dimensional conductive structure a rough surface, the overall surface area can be increased to improve the reaction efficiency with the biological material to be detected.
[0044] The extended field-effect biodetection chip provided by this invention has at least the following beneficial effects. First, its simple structure enables the detection of multiple biological materials. Only a conductive conduction layer and a conductive detection layer need to be sequentially formed on a substrate. Multiple detection electrodes are then placed on the conductive detection layer, and multiple conductive connection pathways are formed on the conductive conduction layer. This allows multiple biological probes to be connected to multiple signal output components, transmitting the detection results for multiple different biological materials to multiple different external hardware such as integrated circuits for processing the corresponding electrical signals, thereby achieving the detection of multiple biological materials. Second, no transistors or integrated circuits are placed on the substrate; instead, the signal output components connect to external hardware capable of processing electrical signals. Since the connection to external hardware does not need to be integrated and fixed, but can be made into a disposable connection structure, in the event of negative situations such as biocontamination or when switching to different external hardware, only the extended electrode portion needs to be discarded, without discarding the external hardware used to process electrical signals. Alternatively, it can be cleaned after separation from one external hardware before connecting to a new one, significantly reducing hardware costs. Furthermore, the presence of multiple recesses allows for the placement of different detection electrodes, which can then be connected to various biological probes, reducing the likelihood of mutual interference. The fact that the detection electrodes protrude above the dielectric layer also expands the contact area of the biological probes, facilitating reactions with the target biological material. Moreover, the staggered arrangement of different types of detection electrodes can form a composite, extended field-effect biodetection chip, increasing the flexibility in detecting various biological materials. Attached Figure Description
[0045] The above and other features, advantages, and aspects of the embodiments of this disclosure will become more apparent from the accompanying drawings and the following detailed description. In the drawings, the same or similar reference numerals denote the same or similar elements.
[0046] Figures 1A This is a schematic diagram illustrating the extended gate field-effect transistor commonly used in previous technologies.
[0047] Figures 1B to 1L As a schematic diagram, the abstract presents the basic architecture and related variations of the ion-sensitive field-effect transistor proposed in this invention.
[0048] Figures 2A to 2C As a schematic diagram, the abstract presents a basic architecture of the extended field-effect biodetection chip proposed in this invention.
[0049] Figures 3A to 3D The diagram illustrates another basic architecture of the extended field-effect biodetection chip proposed in this invention.
[0050] Figures 3E to 3HFor illustration, another basic architecture of the extended gate field effect bio-detection chip is presented.
[0051] Component number explanation
[0052] 11 extended gate field effect transistor
[0053] 12 ion sensitive field effect transistor
[0054] 100 substrate
[0055] 101 gate
[0056] 102 source
[0057] 103 drain
[0058] 104 first conductive structure
[0059] 105 floating gate
[0060] 106 second conductive structure
[0061] 107 first additional conductive structure
[0062] 108 second additional conductive structure
[0063] 109 dielectric layer
[0064] 1095 conductor nano-particle
[0065] 200 extended gate field effect bio-detection chip
[0066] 201 substrate
[0067] 202 dielectric layer
[0068] 203 conductive conducting layer
[0069] 204 conductive detection layer
[0070] 205 signal output component
[0071] 206 reference electrode
[0072] 207 biological probe
[0073] 300 extended gate field effect bio-detection chip
[0074] 301 substrate
[0075] 302 dielectric layer
[0076] 3021 first dielectric layer
[0077] 3022 second dielectric layer
[0078] 3023…third dielectric layer
[0079] 303…conductive transmission layer
[0080] 3034…communication groove
[0081] 3035…recessed opening
[0082] 3036…additional communication groove
[0083] 304…conductive detection layer
[0084] 3041…first detection electrode
[0085] 3042…second detection electrode
[0086] 3043…communication section
[0087] 3044…protruding section
[0088] 3045…extending section
[0089] 305…signal output component
[0090] 306…reference electrode
[0091] 307…conductive connection path
[0092] 3071…first conductive connection path
[0093] 3072…second conductive connection path
[0094] 308…biological probe
[0095] 309…surface modification layer DETAILED DESCRIPTION
[0096] The specific embodiments of the present application will now be described in detail with reference to the accompanying drawings. It should be appreciated that the detailed description of the specific embodiments is merely intended for explaining and illustrating the present application, and is not intended to limit the present application.
[0097] The endpoints of the ranges and any values disclosed herein are not limited to the precise values recited as exactly that endpoint. Any values that fall within common
[0098] Some embodiments of the present application are directed to an ion-sensitive field effect transistor. The main difference from the prior art and the main features of the present application can be summarized as follows: Figures 1A to 1Dshow.
[0099] First, such as Figure 1A As shown, the extended gate field-effect transistor 11 commonly used in the prior art can be described as having a gate 101 on a substrate 100, and a source 102 and a drain 103 located within the substrate 10 and respectively on both sides of the gate 101. It also has a first conductive structure 104 extending along a direction perpendicular to the surface of the substrate 10 and connected at one end to the gate 101, and a floating gate 105 located above the substrate 100, separate from the substrate 100, and connected to the other end of the first conductive structure 104. Here, the first conductive structure 104 is formed by alternating connections of at least one metal interconnect. Of course, the specific design of the first conductive structure 104 can also use a combination of at least one silicon via and at least one metal interconnect. Since both metal interconnects and silicon vias are known technologies, they do not need to be described in detail. Obviously, the extended gate field-effect transistor 11 commonly used in the prior art can be said to be formed on the substrate 100 and the transistor formed by the gate 101, the source 102 and the drain 103 together, forming a T-shaped structure connected to the gate 101, which is formed by two conductive materials, the first conductive structure 104 and the floating gate 105, so as to react with the biological material to be detected.
[0100] In contrast, such as Figures 1B to 1DSome embodiments of the ion-sensitive field-effect transistor 12 according to the present application are shown. The ion-sensitive field-effect transistor 12, e.g. a three-dimensional truncated ion-sensitive field-effect transistor, can basically be said to comprise at least a second conducting structure 106 in addition to the T-shaped structure, wherein any second conducting structure 106 is separated from the substrate 100 and from other second conducting structures 106, but is either connected to the first conducting structure 104 or to the floating gate 105 (or to the T-shaped structure). That is, all second conducting structures 106 can be connected to the floating gate 105, or all second conducting structures 106 can be connected to the first conducting structure 104, or some second conducting structures 106 can be connected to the floating gate 105 and some second conducting structures 106 can be connected to the first conducting structure 104. By using second conducting structures 106 in contact with the T-shaped structure, and in particular by adjusting the total area of all second conducting structures 106 or even the position and size of each second conducting structure 106, the present application can increase the surface area of the conductor material that can react with the biological material to be detected and that is connected to the transistor gate 101, and can even adjust the distribution (or profile) of the conductor material that can react with the biological material to be detected and that is connected to the transistor gate 101, compared to the T-shaped structure of the prior art. Obviously, by using second conducting structures 106, the ion-sensitive field-effect transistor 12 according to the present application will have more surface that can react with the biological material to be detected and a larger surface area than the extended gate field-effect transistor 11 of the prior art, when using the same T-shaped structure and the same occupied substrate 100 area. By this, not only the reaction rate with the biological material to be detected can be increased, but also the electrical properties between the biological material to be detected can be adjusted.
[0101] Further, as Figure 1EAs shown, at least one first additional conductive structure 107 can also be used to further increase the difference between the present application and the T-shaped structure used in the prior art. Here, any first additional conductive structure 107 is separated from the substrate 100, the floating gate 105, the first conductive structure 104, and other first additional conductive structures 107. Any first additional conductive structure 107 is connected to a certain second conductive structure 106 and extends in a direction perpendicular to the surface of the substrate 100. That is, the profile of the conductor material (or the combination of at least one second conductive structure 106 and at least one first additional conductive structure 107) connecting the substrate 100 and the floating gate can be made more varied, especially with more branches perpendicular to the surface of the substrate, to further increase the surface and surface area that can react with the biological material to be detected, and to further adjust the electrical properties between the biological material to be detected.
[0102] Further, as shown in FIG. 1, at least one second additional conductive structure 108 can also be used to further increase the difference between the present application and the T-shaped structure used in the prior art. As shown in FIG. 1, any second additional conductive structure 108 is separated from the substrate 100, the floating gate 105, the first conductive structure 104, the second conductive structures 106, and other second additional conductive structures 108. Any second additional conductive structure 108 is connected to a certain first additional conductive structure 107 and extends in a direction parallel to the surface of the substrate 100. That is, the profile of the conductor material (or the combination of at least one second conductive structure 106 and at least one first additional conductive structure 107 or even at least one second additional conductive structure 108) connecting the substrate 100 and the floating gate can be made more varied, especially with more branches perpendicular to the surface of the substrate 100 and more branches parallel to the surface of the substrate 100, to further increase the area that can react with the biological material to be detected, and to further adjust the electrical properties between the biological material to be detected. Figures 1F to 1H Figure 1F Further, as shown in FIG. 1, at least one second additional conductive structure 108 can also be used to further increase the difference between the present application and the T-shaped structure used in the prior art. As shown in FIG. 1, any second additional conductive structure 108 is separated from the substrate 100, the floating gate 105, the first conductive structure 104, the second conductive structures 106, and other second additional conductive structures 108. Any second additional conductive structure 108 is connected to a certain first additional conductive structure 107 and extends in a direction parallel to the surface of the substrate 100. That is, the profile of the conductor material (or the combination of at least one second conductive structure 106 and at least one first additional conductive structure 107 or even at least one second additional conductive structure 108) connecting the substrate 100 and the floating gate can be made more varied, especially with more branches perpendicular to the surface of the substrate 100 and more branches parallel to the surface of the substrate 100, to further increase the area that can react with the biological material to be detected, and to further adjust the electrical properties between the biological material to be detected. Figure 1G Figure 1H As shown, the number of second additional conductive structures 108 is plural. Each of the plural second additional conductive structures 108 extends along a direction parallel to the surface of the substrate 100. Any of the second additional conductive structures 108 is separated from the substrate 100, the floating gate 105, the first conductive structure 104, and other second additional conductive structures 108. Some of the plural second additional conductive structures 108 are connected to the second conductive structure 106, and some of the plural second additional conductive structures 108 are connected to the first additional conductive structure 107. That is, the profile of the conductor material (or the combination of at least one second conductive structure 106 and at least one first additional conductive structure 107 or even at least one second additional conductive structure 108) connecting the substrate 100 and the floating gate can be varied more, especially with more branches extending perpendicular to the surface of the substrate 100 and more branches extending parallel to the surface of the substrate 100, thereby increasing the area available for reaction with the biological material to be detected and even adjusting the electrical properties between the biological material to be detected.
[0103] That is, by using the second conductive structure 106, the first additional conductive structure 107, and the second additional conductive structure 108, the ion-sensitive field effect transistor 12 can have a T-shaped structure with conductor material extending around, a T-shaped structure with conductor material extending upward, or even a T-shaped structure with conductor material extending both around and upward. In particular, by having the conductor material above the floating gate 105 and the conductor material on both sides of the first conductive structure 104 not extending too much along the direction parallel to the surface of the substrate 100, for example, having the conductor material above the floating gate 105 and the conductor material on both sides of the first conductive structure 104 not extending along the direction parallel to the surface of the substrate 100 more than the extension of the T-shaped structure along the direction parallel to the surface of the substrate 100 or, for example, having the conductor material above the floating gate 105 and the conductor material on both sides of the first conductive structure 104 not extending along the direction parallel to the surface of the substrate 100 more than the edge of the extension of the T-shaped structure along the direction parallel to the surface of the substrate 100, the number of surfaces available for reaction with the biological material to be detected and the total surface area can be significantly increased without significantly increasing or even increasing the area occupied by the substrate 100.
[0104] In addition, the number of second conductive structures 106, the number of first additional conductive structures 107, and the number of second additional conductive structures 108 can be selected. Also, how the one or more first additional conductive structures 107 and the one or more second additional conductive structures 108 are combined and connected to the T-shaped structure can be selected. Depending on how the ion-sensitive field effect transistor 12 and the biological material to be detected can be simultaneously considered to maximize the reaction area, not occupy too much area of the substrate 100, and reduce signal attenuation and sensitivity reduction caused by capacitance. The above figures are only some examples commonly used in previous tests and do not limit the possible variations of the present application.
[0105] By the way, the second conductive structure 106, the additional first conductive structure 107 and the additional second conductive structure 108 can be formed by using commercial semiconductor processes, such as stacking metal-in- via and through-silicon via on the surface of the substrate 100, or such as forming a piece of conductor material / metal on the surface of the substrate 100, without any special technical difficulty and without the need of developing any special process technology.
[0106] Of course, in order to protect the conductive structures (the first conductive structure 104, the floating gate 105, the second conductive structure 106, the additional first conductive structure 107 and the additional second conductive structure 108) from the effects of subsequent processes or accidental impacts and incidental impurity particles, as in the prior art, or in order to adjust the interaction between the conductive structures and the biological material to be detected (for example, to adjust the electrical properties between them, such as the dielectric coefficient, the capacitance related to the relative distance and the relative distance), a dielectric layer 109 can also be included between the conductive structures and the biological material to be detected, or covering the conductive structures before the biological material to be detected is applied. For example, Figure 1I And Figure 1J As shown, the dielectric layer 109 can be a dielectric layer 109 (for example, a dielectric layer 109 with a cuboid profile) located on the substrate 100 and covering the first conductive structure 104, the floating gate 105 and all the second conductive structures 106, or can be a dielectric layer 109 located on the substrate 100 and conformally distributed on the surfaces of the first conductive structure 104, the floating gate 105, all the second conductive structures 106 and all the additional first conductive structures 107, or can be a dielectric layer 109 located on the substrate 100 and conformally distributed on the surfaces of the first conductive structure 104, the floating gate 105, all the second conductive structures 106, all the additional first conductive structures 107 and all the additional second conductive structures 108. The former has the advantage of simple process, only a whole layer of dielectric is formed first, and then a lithography process is used to leave only the part of the dielectric layer that is needed. The latter has the advantage of better electrical performance, when the biological material to be detected is often a solution, the conformally distributed dielectric layer has the same thickness on all the conductor materials directly or indirectly connected to the gate, that is, it is easy to control the capacitance value between the conductor material and the material to be detected.
[0107] It is important to emphasize that the main focus of the present application is on changing the profile of the conductor material connected to the transistor, and not on the materials of the proposed parts of the ion-sensitive field effect transistor 12. For example, the material of the dielectric layer 109 can use any known, developing or future dielectric material, such as silicon dioxide (SiO2) commonly used to protect semiconductor structures, or for example titanium nitride (TiN) that can reduce the capacitance value caused by the voltage difference across it. For example, the possible material of the floating gate 105, the first conductive structure 104, any of the second conductive structures 106, any of the first additional conductive structures 107, and any of the second additional conductive structures 108 includes aluminum, copper, silver, gold or any combination of these materials, and of course other metals or conductive materials (such as conductive polymer materials) can be used.
[0108] Further, in order to increase the reaction area with the material to be detected, conductor nano-particles can also be used to increase the surface area of at least one of the conductive structures connected to the gate 101 and the floating gate 105 (or in other words at least one of the conductor materials), or even to directly increase the surface area of the floating gate 105 and the gate 101. For example, a plurality of metal conductor nano-particles are formed on at least one surface of the floating gate 105, the first conductive structure 104, any of the second conductive structures 106, any of the first additional conductive structures 107, and / or any of the second additional conductive structures 108, thereby forming a relief surface to increase the overall surface area, thereby improving the sensitivity to surface charge changes. Of course, a plurality of conductor nano-particles can also be directly used as the second conductive structure, the first additional conductive structure, and / or the second additional conductive structure, i.e. a plurality of nano-particles can be formed on one or more surfaces of the T-shaped structure to increase the surface area of the T-shaped structure, thereby improving the extended gate field effect transistor 11 of the prior art. In general, in order to simplify the structure of the formed conductive structure (or in other words the conductor material) and to simplify the manufacturing process of the related conductor material and nano-particles, it is relatively simple to make any of the conductive structures and the plurality of nano-particles located thereon have the same material. Of course, the present application does not need to limit these details, as long as the plurality of conductor nano-particles of any of the conductive structures can be secured on the conductive structure, and as long as any of the conductive structures and the plurality of nano-particles located thereon can transmit electrical signals to each other without significant noise. In addition, parameters such as the size of the nano-particles used, whether the plurality of nano-particles are uniformly distributed on different surfaces or have different distribution densities on different surfaces, whether the materials of the nano-particles used on different conductor materials are the same, and the like, can be selected and adjusted. Here, Figure 1K With Figure 1LTwo examples of using nanoparticles are shown. There can be many variations as to how the nanoparticles 1095 are distributed on which surface or surfaces of which conductor material or materials, and no particular variation is specifically illustrated. For example, the nanoparticles 1095 can be on the upper surface of the floating gate 105, or the nanoparticles 1095 can be on one or more surfaces (not necessarily the upper surface, but also a combination of upper and lower surfaces) of the floating gate 105, or the nanoparticles 1095 can be on the upper surface of the uppermost of the second conductive structures 106, or the nanoparticles 1095 can be on one or more surfaces (not necessarily the upper surface, but also a combination of side and lower surfaces) of the uppermost of the second conductive structures 106, or the nanoparticles 1095 can be on the upper surface of at least one of the second conductive structures 106 (not necessarily the uppermost second conductive structure 106, which is the farthest from the substrate 100), or the nanoparticles 1095 can be on a surface (not necessarily the upper surface, but also a lower surface) of at least one of the second conductive structures 106, or the nanoparticles 1095 can be on the upper surface of the uppermost of the first additional conductive structures 107, or the nanoparticles 1095 can be on a surface (not necessarily the upper surface, but also a side surface) of the uppermost of the first additional conductive structures 107, or the nanoparticles 1095 can be on the upper surface of at least one of the first additional conductive structures 107 (not necessarily the uppermost first additional conductive structure 107, which is the farthest from the substrate 100), or the nanoparticles 1095 can be on a surface (not necessarily the upper surface, but also not necessarily the uppermost first additional conductive structure 107, which is the farthest from the substrate 100) of at least one of the first additional conductive structures 107, or the nanoparticles 1095 can be on the upper surface of the uppermost of the second additional conductive structures 108, or the nanoparticles 1095 can be on a surface (not necessarily the upper surface, but also a combination of upper and lower surfaces) of the uppermost of the second additional conductive structures 108, or the nanoparticles 1095 can be on the upper surface of at least one of the second additional conductive structures 108 (not necessarily the uppermost second additional conductive structure 108, which is the farthest from the substrate 100), or the nanoparticles 1095 can be on a surface (not necessarily the upper surface, but also a combination of lower and side surfaces) of at least one of the second additional conductive structures 108 (not necessarily the uppermost second additional conductive structure 108, which is the farthest from the substrate 100). It should be understood that the nanoparticles 1095 are not in contact with the gate 101.
[0109] Some embodiments of the present application relate to an extended field effect bio-detection chip. As Figure 2A and Figure 2BAs shown, the extended field effect bio-detection chip 200 basically comprises a substrate 201, a dielectric layer 202, a conductive transmission layer 203, a conductive detection layer 204, a signal output component 205, and a reference electrode 206. For the sake of illustration, in Figure 2B the conductive transmission layer 203 is shown in dashed line to represent that the conductive transmission layer 203 is below the dielectric layer 202, the conductive detection layer 204, and the reference electrode 206. The conductive transmission layer 203 is on the substrate 201, and the conductive detection layer 204 is on the conductive transmission layer 203. In addition, the dielectric layer 202 surrounds the conductive transmission layer 203 and the conductive detection layer 204, not only the sidewalls thereof, but also part of the upper surfaces thereof. One end of the signal output component 205 is on the substrate 201, surrounded by the dielectric layer 202, i.e. connected to the conductive transmission layer 203 and / or the conductive detection layer 204, and the other end thereof is separated from the substrate 201, the dielectric layer 202, the conductive transmission layer 203, and the conductive detection layer 204, i.e. connected to hardware outside the extended field effect bio-detection chip, such as integrated circuits, cell phones, notebook computers, etc., which can process electrical signals. The reference electrode 207 is connected to the conductive transmission layer 203, and can provide a reference for electrical signals. Of course, since the conductive transmission layer 203 and the conductive detection layer 204 need to react with the biological material to be detected, receive the reference provided by the reference electrode 207, and transmit the electrical signals related to the biological material to be detected to the outside through the signal output component 205, the conductive transmission layer 203 and the conductive detection layer 204 need to be divided into several separate parts.
[0110] Obviously, as shown in Figure 2C the conductive detection layer 204, the electrical signals generated by the reaction between the biological probe 207 and the biological material can be transmitted to the outside of the extended field effect bio-detection chip 200 through the conductive detection layer 204, the conductive transmission layer 203, and the signal output component 205 when the biological material to be detected contacts the extended field effect bio-detection chip 200. Of course, when the types of biological materials to be detected are various and / or the types are various, multiple biological probes 207 can be used. However, in order to avoid confusion of the respective electrical signals, the conductive detection layer 204 and the conductive transmission layer 203 need to be divided into multiple parts, respectively, to form multiple electrical signal transmission channels in combination with the biological probes 207. Here, the biological probe 207 can be directly fixed (or said to be embedded) on the conductive detection layer 204, or placed on the conductive detection layer 204 as needed by the biological material to be detected, and different embodiments of the present application cover these variations.
[0111] The specific design of the signal output component 205 can have many variations, such as a wire, a connector, or a plug-in terminal, as long as it can be connected to or detached from the external hardware for processing electrical signals, so that the stretchable field-effect bio-detection chip 200 can be connected to different external hardware for processing electrical signals as needed, or so that the same external hardware for processing electrical signals can be connected to different stretchable field-effect bio-detection chips 200 as needed. In this way, the stretchable field-effect bio-detection chip 200 that has been damaged or is not suitable for processing the biological material to be detected can be discarded and replaced with a good or suitable stretchable field-effect bio-detection chip 200 when needed. Of course, the external hardware for processing electrical signals that needs to be used can also be replaced when needed. As for how the signal output component 205 is connected to the outside, there is no limitation, whether it is connected out from the bottom (or back) of the substrate 201 after passing through the substrate 201, or it is connected out from the two sides of the substrate 201 after passing along (or parallel to) the surface of the substrate 201. Incidentally, when a packaging shell is applied to protect the stretchable field-effect bio-detection chip 200, the packaging shell is located on the bottom and two sides of the stretchable field-effect bio-detection chip 200, and the signal output component 205 can be directly connected to the outside through the packaging shell, or can be connected to the outside by bypassing the opening (or edge) of the packaging shell.
[0112] Another embodiment of the present application relates to a stretchable field-effect bio-detection chip. As shown in Figures 3A to 3D , the stretchable field-effect bio-detection chip 300 at least includes a substrate 301, a dielectric layer 302, a conductive transmission layer 303, a conductive detection layer 304, a signal output component 305, and a reference electrode 306. For ease of illustration, in Figure 3D , the conductive transmission layer 303 is shown in dashed lines to represent that the conductive transmission layer 303 is below the dielectric layer 302, the conductive detection layer 304, and the reference electrode 306.
[0113] Here, the conductive transmission layer 303 is not a whole layer of conductive material, but is composed of a plurality of conductive connection paths (such as a first conductive connection path 3071 and a second conductive connection path 3072) formed by a plurality of segments of conductive material separated from each other.
[0114] In this embodiment, the conductive detection layer 304 is not a single conductive material, but a plurality of first detection electrodes 3041 formed by a plurality of segments of conductive material separated from each other. The first detection electrodes 3041 are respectively connected to the conductive connection paths (e.g. the first conductive connection path 3071 and the second conductive connection path 3072), and thus can be respectively connected to different hardware for processing the electrical signals from the outside via different signal output components 305. The first detection electrodes 3041 can be arranged in groups, each group having one or more first detection electrodes 3041. The number of first detection electrodes 3041 in each group, the relative distance and direction between the first detection electrodes 3041 in each group, and the relative distance and direction between the groups can be adjusted according to the type, number and kind of biological probes. In this embodiment, only one possible arrangement of the groups of first detection electrodes 3041 is shown. In addition, the cross-sectional profile of each first detection electrode 3041 is not particularly limited, and can be circular, diamond, square, rectangular or even other polygonal shapes.
[0115] In this embodiment, different types of biological probes 308 can be respectively carried on the first detection electrodes 3041. In order to facilitate the fixation of the biological probes 308 on the first detection electrodes 3041, or to reduce the obstruction of the transmission of electrical signals between the biological probes 308 and the first detection electrodes 3041, a surface modification layer 309 can be provided on each first detection electrode 3041. Since there are many known techniques for the surface modification layer 309, the profile, thickness and material of the surface modification layer 309 are not particularly limited in this embodiment, and the detailed description of the surface modification layer 309 is omitted.
[0116] In some embodiments, the dielectric layer 302 includes a first dielectric layer 3021, a second dielectric layer 3022, and a third dielectric layer 3023. The first dielectric layer 3021 is directly on the substrate 301, and the conductive layer 303 is on the first dielectric layer 3021. The second dielectric layer 3022 is directly on the conductive layer 303 and covers (or encompasses) the conductive layer 303, and the second dielectric layer 3022 has a plurality of through-holes 3034 (or holes) so that the bottom of the conductive detection layer 304 can pass through the through-holes 3034 to contact (or so that electrical signals can be transmitted between) the conductive layer 303. The conductive detection layer 304 is also on (or covers the top surface of) the second dielectric layer 3022. The third dielectric layer 3023 is on the second dielectric layer 3022 and covers (or encompasses) the conductive detection layer 304. The third dielectric layer 3023 has a plurality of recesses 3035 on the first detection electrodes 3041 to respectively hold the same or different biological probes 308. The profile and size of each recess 3035 substantially depend on the profile and size of the biological probe to be held. For example, in some embodiments, the depth of the recess 3035 is about 1 μm to 5 μm, and the distance between adjacent first detection electrodes 3041 is about 30 μm to 50 μm. In addition, each recess 3035 can also be used to hold a respective reference electrode 306, each of which has a bottom surface in contact with the first detection electrode 3041 and an upper surface higher than the upper surface of the third dielectric layer 3023. When the reference electrodes 306 are directly positioned on the upper surface of the first detection electrodes 3041, accurate positioning can be achieved, and a stable potential can be applied.
[0117] Additionally, the substrate 301 can be any substrate used in semiconductor processing, whether the most common silicon wafer or even a glass substrate, a flexible substrate, or a III-V wafer. The material of the dielectric layer 302 can be silicon oxide, silicon nitride, a polyimide film, or a polymer. The materials of the conductive layer 303 and the conductive detection layer 304 can be aluminum copper, aluminum silicon copper, titanium gold, titanium nitride, gold, or other conductor materials.
[0118] Still other embodiments of the present application relate to an extended field effect bio-detection chip, as shown in FIG. 4. The main difference between these embodiments and the previous embodiments is the details of the conductive detection layer 304, which includes a plurality of first detection electrodes 3041 and a plurality of second detection electrodes 3042. Therefore, the following description will focus on the differences and corresponding changes in the conductive detection layer 304, and the same parts of these embodiments and the previous embodiments will not be repeated. For ease of illustration, the following description will be made with reference to the first detection electrodes 3041 and the second detection electrodes 3042 as examples of the first detection electrodes 3041 and the second detection electrodes 3042, respectively. Figures 3E to 3H Still other embodiments of the present application relate to an extended field effect bio-detection chip, as shown in FIG. 4. The main difference between these embodiments and the previous embodiments is the details of the conductive detection layer 304, which includes a plurality of first detection electrodes 3041 and a plurality of second detection electrodes 3042. Therefore, the following description will focus on the differences and corresponding changes in the conductive detection layer 304, and the same parts of these embodiments and the previous embodiments will not be repeated. For ease of illustration, the following description will be made with reference to the first detection electrodes 3041 and the second detection electrodes 3042 as examples of the first detection electrodes 3041 and the second detection electrodes 3042, respectively.Figure 3H In some embodiments, the first conductive connection paths 3071 and the second conductive connection paths 3072 are shown in dashed lines to indicate that the first conductive connection paths 3071 and the second conductive connection paths 3072 are underneath the first detection electrodes 3041, the second detection electrodes 3042, and the signal output components 305.
[0119] In some embodiments, the second detection electrodes 3042 are identical to the first detection electrodes 3041, and are respectively connected to the first conductive connection paths 3071 and the second conductive connection paths 3072 of the conductive layer 303, and are respectively connected to different hardware for processing the electrical signals from the outside via the different signal output components 305. In some embodiments, the first detection electrodes 3041 and the second detection electrodes 3042 can further have a surface modification layer 309 disposed thereon to more effectively immobilize the biological probes 308.
[0120] In some embodiments, the lower surfaces of the first detection electrodes 3041 are in contact with the conductive layer 303, and the upper surfaces of the first detection electrodes 3041 are exposed and below the upper surface of the dielectric layer 302, such that the upper surfaces of the first detection electrodes 3041 are recessed from the upper surface of the dielectric layer 302. In some embodiments, each of the second detection electrodes 3042 includes a connecting section 3043 and a protruding section 3044. The connecting section 3043 is disposed within the dielectric layer 302 and has a lower surface in contact with the conductive layer 303. The protruding section 3044 protrudes from the upper surface of the dielectric layer 302 and has a cross-sectional shape that can be any shape, such as a circular shape, an elliptical shape, a quadrilateral shape, or a polygonal shape. The top surface and the side surface of the protruding section 3044 that protrude from the upper surface of the dielectric layer 302 can be in contact with the biological probes. In some embodiments, the profile and the size of the protruding section 3044 affect the reaction area and thus affect the sensitivity of the entire extended field effect bio-detection chip.
[0121] In these embodiments, the first detection electrodes 3041 and the second detection electrodes 3042 can be arranged in groups. The details of the group arrangement, such as how many first detection electrodes 3041 or second detection electrodes 3042 are in each group, and the relative geometric relationship between the groups, depend on the type and number of biological probes corresponding to the groups. In some specific designs, the first detection electrodes 3041 and the second detection electrodes 3042 are arranged in groups respectively, and each group of first detection electrodes 3041 and each group of second detection electrodes 3042 are interleaved with each other. In other specific designs, the first detection electrodes 3041 and the second detection electrodes 3042 are arranged in groups respectively, and each group of second detection electrodes 3042 is located between two adjacent groups of first detection electrodes 3041, such that an adjacent first detection electrode 3041 and a second detection electrode 3042 together carry a specific biological probe. That is, by properly adjusting the distance and relative position between the adjacent groups of first detection electrodes 3041 and second detection electrodes 3042, the groups of first detection electrodes 3041 and the groups of second detection electrodes 3042 can carry suitable biological probes respectively or together. As an example, in some specific designs, the depth of each recess 3035 is between 1 μm and 5 μm, the distance between the first detection electrodes 3041 in the same group is between 30 μm and 150 μm, the distance between the second detection electrodes 3042 in the same group is between 30 μm and 150 μm, and the distance between the first detection electrodes 3041 and the second detection electrodes 3042 in adjacent groups is between 300 μm and 500 μm.
[0122] In different specific designs, the protruding section 3044 can have different profiles and different sizes. For example, it can be a sharp shape with the cross-sectional area gradually decreasing from the bottom to the top, and the cross-sectional shape can be circular, quadrangular, or polygonal. For example, the overall profile of the protruding section 3044 with a circular cross-section is a circular truncated cone or a circular cone. The ratio of the height of the protruding section 3044 to the width of the cross-section can also be adjusted to adjust the surface area of the entire second detection electrode 3042 to facilitate the combination with the biological probe. In some specific designs, when the ratio is greater than or equal to ten, the protruding section 3044 can sufficiently combine with the biological probe and sufficiently react with the biological material to be detected. In general, a high ratio value can provide a needle-like structure for easy charging and discharging to enhance the reaction with the biological material, and can also be applied to the use of non-invasive patches or multiple groups of electrodes.
[0123] In other embodiments, each second detection electrode 3042 includes an extension segment 3045 in addition to the connection segment 3043 and the protrusion segments 3044. In this embodiment, the connection segment 3043 and the protrusion segments 3044 are similar to those in the previous embodiment. In this embodiment, each set of second detection electrodes 3042 has an extension segment 3045 that is positioned above and connects all of the protrusion segments 3044 to each other. In this way, the configuration of the second detection electrodes 3042 in the same set can be designed to control the flow of fluid so that the solution containing the biological material to be detected can flow smoothly through the second detection electrodes 3042 or through the biological probes connected to the second detection electrodes 3042, thereby allowing sufficient reaction to occur.
[0124] The first detection electrodes 3041 can be further connected to a reference electrode 306 that has a top surface that is higher than the top surface of the dielectric layer 302. The reference electrode 306 can be positioned directly on the top surface of the first detection electrodes 3041 to provide a stable potential. The reference electrode 306 can have any shape, size, and material, and can be made using any known technique.
[0125] In some embodiments, the third dielectric layer 3023 has additional through-holes 3036 (or holes) in addition to the recesses 3035 above the first detection electrodes 3041. The recesses 3035 are used to hold the same or different biological probes (not shown), and the additional through-holes 3036 are used to allow the protrusion segments 3044 to pass through and connect to the connection segments 3045, where the other ends of the protrusion segments 3044 protrude above the top surface of the third dielectric layer 3023.
[0126] Other embodiments of the present application relate to other variations of the extended field effect bio-detection chip, which are not shown. The connection between the conductive connection paths 307 and the first detection electrodes 3041 (or even the second detection electrodes 3042) can not necessarily be one-to-one, but can be many-to-one or one-to-many. For example, in some embodiments, the conductive layer 303 has three conductive connection paths 307, one of which is connected to a circular first detection electrode 3041 and a triangular first detection electrode 3041, another of which is connected to a triangular first detection electrode 3041 and a square first detection electrode 3041, and the other two of which are connected to the same elliptical first detection electrode 3041.
[0127] The connection of the signal output component 305 to the conductive layer 303 or the conductive detection layer 304 is not strictly limited. In different specific designs, depending on the wiring and configuration, the signal output component 305 can be connected to the first detection electrode 3041 or the second detection electrode 3042, and can be connected to the connecting segment 3043 or the protruding segment 3044, or even to the extending segment 3045.
[0128] The above description of the known art is not described in detail, and those skilled in the art can understand it.
[0129] The above description is only some specific embodiments of the present application and does not limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application. The technical scope of the present application is not limited to the content of the specification, and must be determined according to the scope of the claims.
Claims
1. An ion-sensitive field effect transistor, characterized by Comprising: a substrate; a gate disposed on the substrate; a first conductive structure extending along a direction perpendicular to a surface of the substrate, one end of the first conductive structure being connected to the gate; a floating gate connected to the other end of the first conductive structure and separated from the substrate; at least one second conductive structure, the at least one second conductive structure being a plurality of second conductive structures, any one of the at least one second conductive structure being separated from the other second conductive structures, and the at least one second conductive structure all being connected to the first conductive structure.
2. The ion-sensitive field effect transistor according to claim 1, characterized in that Further comprising: at least one first additional conductive structure all extending along a direction perpendicular to the surface of the substrate, the at least one first additional conductive structure being a plurality of first additional conductive structures, any one of the at least one first additional conductive structure being respectively connected to a corresponding second conductive structure, and any one of the first additional conductive structure all being separated from the substrate, the gate, the floating gate, the first conductive structure, and the other first additional conductive structures.
3. The ion-sensitive field effect transistor according to claim 2, characterized in that Further comprising: at least one second additional conductive structure all extending along a direction parallel to the surface of the substrate, the at least one second additional conductive structure being a plurality of second additional conductive structures, any one of the at least one second additional conductive structure being separated from the substrate, the gate, the floating gate, the first conductive structure, and the other second additional conductive structures; wherein the at least one second additional conductive structure is respectively connected to a corresponding first additional conductive structure.
4. The ion-sensitive field effect transistor according to claim 1, characterized in that Further comprising at least one of: a dielectric layer disposed on the substrate and covering the gate, the floating gate, the first conductive structure, and all of the second conductive structures; and a dielectric layer disposed on the substrate and conformally distributed on a plurality of surfaces of the gate, the floating gate, the first conductive structure, and all of the second conductive structures.
5. The ion-sensitive field effect transistor according to claim 2, wherein Further comprising at least one of: a dielectric layer disposed on the substrate and covering the gate, the floating gate, the first conductive structure, all of the second conductive structures, and all of the first additional conductive structures; and a dielectric layer disposed on the substrate and conformally distributed on a plurality of surfaces of the gate, the floating gate, the first conductive structure, all of the second conductive structures, and all of the first additional conductive structures. Further comprising at least one of:
6. The ion-sensitive field effect transistor according to claim 3, characterized in that a dielectric layer disposed on the substrate and covering the gate, the floating gate, the first conductive structure, all of the second conductive structures, all of the first additional conductive structures, and all of the second additional conductive structures; and a dielectric layer disposed on the substrate and conformally distributed on a plurality of surfaces of the gate, the floating gate, the first conductive structure, all of the second conductive structures, all of the first additional conductive structures, and all of the second additional conductive structures. Further comprising at least one of: a material of the dielectric layer being titanium nitride; 7. The ion-sensitive field effect transistor according to claim 4, 5 or 6, characterized in that a material of the dielectric layer being silicon dioxide. 8. The ion-sensitive field effect transistor according to claim 1, 2 or 3, characterized in that Further comprising at least one of: the material of the floating gate comprises at least one of: aluminum, copper, silver, gold; the material of the first conductive structure comprises at least one of: aluminum, copper, silver, gold; the material of the second conductive structure comprises at least one of: aluminum, copper, silver, gold; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the material of any of the first additional conductive structures comprises at least one of: aluminum, copper, silver, gold; and when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the material of any of the second additional conductive structures comprises at least one of: aluminum, copper, silver, gold.
9. The ion-sensitive field effect transistor according to any one of claims 1, 2 or 3, characterized in that, Further comprising a plurality of conductor nanoparticles configured to at least one of: the plurality of conductor nanoparticles are located on an upper surface of the floating gate; the plurality of conductor nanoparticles are located on at least one surface of the floating gate; the plurality of conductor nanoparticles are located on an upper surface of an uppermost one of the second conductive structures; the plurality of conductor nanoparticles are located on at least one surface of an uppermost one of the second conductive structures; the plurality of conductor nanoparticles are located on an upper surface of at least one of the second conductive structures; the plurality of conductor nanoparticles are located on at least one surface of at least one of the second conductive structures; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the plurality of conductor nanoparticles are located on an upper surface of an uppermost one of the first additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the plurality of conductor nanoparticles are located on at least one surface of an uppermost one of the first additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the plurality of conductor nanoparticles are located on an upper surface of at least one of the first additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the plurality of conductor nanoparticles are located on at least one surface of at least one of the first additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the plurality of conductor nanoparticles are located on an upper surface of an uppermost one of the second additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the plurality of conductor nanoparticles are located on at least one surface of an uppermost one of the second additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the plurality of conductor nanoparticles are located on an upper surface of at least one of the second additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the plurality of conductor nanoparticles are located on at least one surface of at least one of the second additional conductive structures; and the plurality of conductor nanoparticles are used to form at least one of the second conductive structures.
10. The ion-sensitive field effect transistor of claim 1, wherein: the first conductive structure is alternately connected by at least one metal interconnect.
11. An ion-sensitive field effect transistor, characterized by comprising: a substrate; a gate disposed on the substrate; a first conductive structure extending in a direction perpendicular to a surface of the substrate, one end of the first conductive structure being connected to the gate; a floating gate connected to the other end of the first conductive structure and separated from the substrate; and at least one second conductive structure, the at least one second conductive structure being a plurality of second conductive structures, any one of the at least one second conductive structure being separated from the other second conductive structures, and the at least one second conductive structure being connected to the floating gate. Further comprising:
12. The ion-sensitive field effect transistor according to claim 11, characterized in that at least one first additional conductive structure, the at least one first additional conductive structure extending in a direction perpendicular to a surface of the substrate, the at least one first additional conductive structure being a plurality of first additional conductive structures, any one of the at least one first additional conductive structure being connected to a corresponding second conductive structure, and any one of the first additional conductive structure being separated from the substrate, the gate, the floating gate, the first conductive structure, and the other first additional conductive structures. Further comprising:
13. The ion-sensitive field effect transistor according to claim 12, characterized in that at least one second additional conductive structure, the at least one second additional conductive structure extending in a direction parallel to a surface of the substrate, the at least one second additional conductive structure being a plurality of second additional conductive structures, any one of the at least one second additional conductive structure being separated from the substrate, the gate, the floating gate, the first conductive structure, and the other second additional conductive structures; wherein the at least one second additional conductive structure is connected to a corresponding first additional conductive structure. Further comprising at least one of:
14. The ion-sensitive field effect transistor of claim 11, wherein, a dielectric layer disposed on the substrate and covering the gate, the floating gate, the first conductive structure, and all of the second conductive structures; and a dielectric layer disposed on the substrate and conformally distributed on surfaces of the gate, the floating gate, the first conductive structure, all of the second conductive structures. Further comprising at least one of:
15. The ion-sensitive field effect transistor of claim 12, wherein, a dielectric layer disposed on the substrate and covering the gate, the floating gate, the first conductive structure, all of the second conductive structures, and all of the first additional conductive structures; and a dielectric layer disposed on the substrate and conformally distributed on surfaces of the gate, the floating gate, the first conductive structure, all of the second conductive structures, and all of the first additional conductive structures. Further comprising at least one of: a dielectric layer disposed on the substrate and covering the gate, the floating gate, the first conductive structure, all of the second conductive structures, all of the first additional conductive structures, and all of the second additional conductive structures; and 16. The ion-sensitive field effect transistor of claim 13, wherein, a dielectric layer disposed on the substrate and conformally distributed on surfaces of the gate, the floating gate, the first conductive structure, all of the second conductive structures, all of the first additional conductive structures, and all of the second additional conductive structures. Further comprising at least one of: a material of the dielectric layer being titanium nitride; a material of the dielectric layer being silicon dioxide.
17. The ion-sensitive field effect transistor according to claim 14, 15 or 16, characterized in that 18. The ion-sensitive field effect transistor according to claim 11, 12 or 13, characterized in that Further comprising at least one of: the material of the floating gate comprises at least one of: aluminum, copper, silver, gold; the material of the first conductive structure comprises at least one of: aluminum, copper, silver, gold; the material of the second conductive structure comprises at least one of: aluminum, copper, silver, gold; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the material of any of the first additional conductive structures comprises at least one of: aluminum, copper, silver, gold; and when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the material of any of the second additional conductive structures comprises at least one of: aluminum, copper, silver, gold.
19. The ion-sensitive field effect transistor according to any one of claims 11, 12 or 13, characterized in that Further comprising a plurality of conductor nanoparticles configured to at least one of: the plurality of conductor nanoparticles are located on an upper surface of the floating gate; the plurality of conductor nanoparticles are located on at least one surface of the floating gate; the plurality of conductor nanoparticles are located on an upper surface of an uppermost one of the second conductive structures; the plurality of conductor nanoparticles are located on at least one surface of an uppermost one of the second conductive structures; the plurality of conductor nanoparticles are located on an upper surface of at least one of the second conductive structures; the plurality of conductor nanoparticles are located on at least one surface of at least one of the second conductive structures; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the plurality of conductor nanoparticles are located on an upper surface of an uppermost one of the first additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the plurality of conductor nanoparticles are located on at least one surface of an uppermost one of the first additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the plurality of conductor nanoparticles are located on an upper surface of at least one of the first additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one first additional conductive structure, the plurality of conductor nanoparticles are located on at least one surface of at least one of the first additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the plurality of conductor nanoparticles are located on an upper surface of an uppermost one of the second additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the plurality of conductor nanoparticles are located on at least one surface of an uppermost one of the second additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the plurality of conductor nanoparticles are located on an upper surface of at least one of the second additional conductive structures; when the ion-sensitive field effect transistor further comprises at least one second additional conductive structure, the plurality of conductor nanoparticles are located on at least one surface of at least one of the second additional conductive structures; and the plurality of conductor nanoparticles are used to form at least one of the second conductive structures.
20. The ion-sensitive field effect transistor of claim 11, wherein: the first conductive structure is alternately connected by at least one metal interconnect.
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