A biological field effect sensing chip is provided, which includes a substrate, a field effect transistor (FET) is disposed on the first region of the substrate, an insulation layer is encapsulated the FET and the first region and disposed on the surface of the second region of the substrate to expose the second region, an interconnect structure is disposed on the second region. The interconnect structure is located in the opening of the insulation layer and the interconnect structure in the opening sequentially includes a bottom conductive layer, an upper conductive layer and a dielectric layer with conductive plug disposed between the bottom conductive layer and the upper conductive layer, and the bottom conductive layer of the interconnect structure is electrically connected to the FET; and a receptor is arranged on the surface of the upper conductive layer to capture the target(s) of the testing sample.

FIELD OF THE INVENTION

The present invention relates to a filed od detection technology, and in particularly to a biological field effect sensing chip that can detect proteins, bacteria, and viruses.

BACKGROUND OF THE INVENTION

Biosensors are devices that operate based on the electrical, electrochemical, optical and mechanical detection principles and are used to sense and detect biomolecules. Biosensors with transistors can electrically sense charges, photons, and mechanical properties of biomolecules or biological entities. This detection behavior can be achieved through direct detection and induction, or through the reaction or interaction of specific reactants with biomolecules/biological entities. These biosensors can be manufactured by semiconductor processes, which can quickly convert electrical signals, and can be easily applied to integrated circuits (ICs) and microelectromechanical system (MEMs).

Biochip(s) is(are) essentially a miniature laboratory that can perform hundreds or thousands of biochemical reactions simultaneously. Biochip(s) can detect special biomolecules, measure their properties, compute and process signal, and even directly analyze data, so biochip(s) allow researchers to quickly screen large number of biological analytes for purposes ranging from disease diagnosis to detecting biochemical terrorist attacks. Advanced biochip(s) utilize many biosensors alongside fluidic channels for reaction integration, sensing and sample management. BioFET (biological field-effect transistor or bio-organic field-effect transistors) is a biological sensor containing a transistor that can electrically sense biomolecules or biological entities. Although biological field-effect transistor(s) have advantages in many aspects, there are also challenges in their manufacturing and/or operation, such as: issue based on compatibility with semiconductor manufacturing process, biological limitations and/or limits, and there are many challenges that arise in the large-scale integration process, such as the integration of electronic signals and biological applications.

In addition, the existing biosensing chip(s) can only detect the presence/absence of bacteria, viruses or suspended particles, and the range of the detecting region is limited, and the concentration of bacteria, viruses or suspended particles cannot be estimated. In addition, high-sensitivity nanowires designed in a chip-based manner are prone to noise interference, leading misjudgment. Moreover, the nanowires are exposed with polysilicon, which is a special process. However, the most chip factories are unwilling to provide special and customized processes to coordinate production, so the yield cannot be improved, and effective production cannot be achieved.

SUMMARY OF THE INVENTION

The main object of the present invention is to provide a biological field effect sensing chip, which can be manufactured according to the existing complementary metal oxide semiconductor (CMOS) process of the current semiconductor chip factory.

Another object of the present invention is to arrange the multilayer interconnect structure on the same plane as the field effect transistor and keep the distance apart. In addition, the semiconductor manufacturing process technology is used to electrically connect the bottom conductive layer and the field effect transistor during the process of forming a multilayer interconnect structure, so that no additional manufacturing process is required to simplify the manufacturing process and reduce the costs.

Another object of the present invention is to provide good air tightness between the bottom conductive layer and the isolation layer of the multilayer interconnect structure, so the entire biological field effect sensing chip can be used to detect the sample(s) under liquid state, and there will be no problem of liquid overflowing between the bottom conductive layer and the insulation layer to cause the short-circuit of the biological field effect sensing chip.

According to above objects, the present invention provides a biological field effect sensing chip, including a substrate with a first region and a second region, a field effect transistor arranged on the first region of the substrate, an isolation layer covered the field effect transistor on the first region of the substrate and the second region of the substrate, the isolation layer has an opening to expose the surface of the second region, a multilayer interconnect structure arranged on the surface of the second region of the substrate and disposed in the opening of the isolation layer, and the biological field effect transistor and the multilayer interconnect structure are on the same plane, in which the multilayer interconnect structure in the opening sequentially from the surface of the second region of the substrate to the top includes a bottom conductive layer, an upper conductive layer, and at least a dielectric layer with a plurality of conductive plugs are arranged between the bottom conductive layer and the upper conductive layer, the bottom conductive layer and the upper conductive layer are electrically connected through the plurality of conductive plugs, and the bottom conductive layer of the multilayer interconnect structure is electrically connected to the field effect transistor on the first region of the substrate, and a plurality of receptors arranged on the surface of the upper conductive layer to capture at least one of the plurality of targets in the testing sample.

According to above objects, the present invention also provides another biological field effect sensing chip, which includes a substrate having a source region and a drain region, an isolation layer having an opening on the substrate, and the opening is used to expose a surface of the substrate, a gate oxide layer is disposed on the surface of the substrate, a gate electrode is disposed on the gate oxide layer, a multilayer interconnect structure is disposed on the gate electrode, in which the multilayer interconnect structure includes a bottom conductive layer, an upper conductive layer, and a dielectric layer has a plurality of conductive plugs therein and is disposed between the bottom conductive layer and the upper conductive layer, and the four sides of the upper conductive layer are embedded into the insulation layer to expose the portion of a surface of the upper conductive layer, and a plurality of receptors is arranged on an exposed surface of the upper conductive layer to capture at least one of the plurality of targets in a testing sample.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

First, please refer toFIG.1.FIG.1shows a cross-sectional schematic diagram of a biological field effect sensing chip. InFIG.1, a biological field effect sensing chip1is composed of a field effect transistor20and a multilayer interconnect structure40, in which the field effect transistor20and the multilayer interconnect structure40are respectively arranged on a first region10A and a second region10B of the substrate10and the field effect transistor20and the multilayer interconnect structure40are arranged on the same plane. It should be noted that, inFIG.1, the dotted line110is used to divide the substrate10into the first region10A and the second region10B for easy understanding of subsequent descriptions. In fact, there is no dotted line110in the substrate10.

The field effect transistor20is an N-type metal oxide semiconductor (NMOS) for example, the structure of the field effect transistor20at least includes a gate oxide layer201, a gate electrode202, a source region204and a drain region206, in which the source region204and the drain region206are disposed in the first region10A of the substrate10, the gate oxide layer201is disposed on the substrate10, the gate electrode202is disposed on the gate oxide layer201and is disposed between the source region204and the drain region206. In addition, an isolation layer (or field oxide layer)30are further provided on the first region10A and the second region10B of the substrate10. It should be noted that the abovementioned isolation layer30, the gate oxide layer201, the gate electrode202, the source region204and the drain region206are formed by using a suitable complementary metal oxide semiconductor (CMOS) process, and the formation steps are not the major technology features of this invention, it will not be described herein.

Next, an insulation layer402is provided on a surface of the second region10B of the substrate10. It should be noted that the insulation layer402is formed simultaneously with the gate oxide layer201of the field effect transistor20, and then the portion of the insulation layer402is removed by using an etching process. In order to distinction clearly, the insulation layer on the first region10A is defined as the gate oxide layer201, and the insulation layer on the second region10B is defined as the insulation layer402. Next, a bottom conductive layer410is formed on the insulation layer402and the bottom conductive layer410extends in the direction of the field effect transistor20on the same plane and is electrically connected to the gate electrode202of the field effect transistor20. In should be noted that the bottom conductive layer410on the second region10B of the substrate10is used as the first metal layer (metal1) of the multilayer interconnect structure40, and the bottom conductive layer410extends toward the field effect transistor20is used as a connecting layer electrically connected to the gate electrode202. It should be noted that the material of the bottom conductive layer410is gold or copper.

Next, an isolation layer30is arranged on the substrate10, in which the isolation layer30on the first region10A of the substrate10is used to cover the field effect transistor20, the isolation layer30on the second region10B of the substrate10utilizes an etching process of semiconductor manufacturing process to remove the portion of the insulation layer to form an opening302to expose the bottom conductive layer410on the second region10B of the substrate10. In addition, the isolation layer30also covers the portion of the bottom conductive layer410extending toward the field effect transistor20. Next, a first dielectric layer412is formed on the bottom conductive layer410by using the semiconductor process technology. An etching process is used to remove the portion of the first dielectric layer412, so that a plurality of first via holes (not shown) is formed in the first dielectric layer412. Subsequently, the conductive material such as copper, tungsten, titanium, or tantalum or their metal compounds is deposed or electroplated into the plurality of first via holes to form a plurality of first conductive plugs510.

Next, an intermediate conductive layer414is formed on the first dielectric layer412having the plurality of first conductive plugs510, so that the intermediate conductive layer414is electrically connected to the bottom conductive layer410through the plurality of conductive plugs510in the first dielectric layer412. Then, a second dielectric layer416is formed on the intermediate conductive layer414by using another deposition process, the manufacturing process is similar to the aforementioned steps of forming a plurality of via holes (not shown), an etching step is used to remove the portion of the second dielectric layer416to form a plurality of via holes (not shown) in the second dielectric layer416. Similarly, the conductive material such as copper, tungsten, titanium, or tantalum or their metal compounds is deposed or electroplated into the plurality of second via holes to form a plurality of second conductive plugs512. Finally, an upper conductive layer418is deposited on the second dielectric layer416having the plurality of second conductive plugs512, in which the upper conductive layer418is electrically connected to the intermediate conductive layer414through the plurality of second conductive plugs512. Furthermore, the upper conductive layer418and the bottom conductive layer410are electrically connected through the plurality of second conductive plugs512, the intermediate conductive layer414and a plurality of first conductive plugs510.

There is a plurality of receptors60is further arranged on the upper conductive layer418of the multilayer interconnect structure40, in which the plurality of receptors60is used to capture the target (not shown) in the testing sample (not shown). It should be noted that the above multilayer interconnect structure40is composed of the bottom conductive layer410, the first dielectric layer412having a plurality of first conductive plugs510, the intermediate conductive layer414, the second dielectric layer416with the plurality of second conductive plugs512, and the upper conductive layer418. In one embodiment of this invention, the multilayer interconnect structure40is composed of the bottom conductive layer410, the upper conductive layer418and the first dielectric layer412with the plurality of first conductive plugs510between the bottom conductive layer410and the upper conductive layer418. In another embodiment of this invention, the multilayer interconnect structure40is formed by a stagged stack of four, five or more conductive layers and the dielectric layer having the plurality of conductive plugs between each the conducive layers. However, no matter how many layers of conductive layers and the dielectric layer are interlaced, the multilayer interconnect structure40is electrically connected through the bottom conductive layer410extending toward the gate electrode202of the field effect transistor20and serving as a connecting layer, the surface of the uppermost layer of the multilayer interconnect structure40is the surface of the upper conductive layer418, the surface of the upper conductive layer418is arranged a plurality of receptors60to capture at least one of the plurality of targets (not shown) in the testing sample (not shown), in which the plurality of receptors60is fixed on the upper conductive layer418by an immobilized method during the antibody processing after the production of the biological field effect sensing chip1. Accordingly, in this invention, the multilayer interconnect structure40having a plurality of receptors60on the second region10B of the substrate10is defined as a detecting region or sensing region.

Please continue to refer toFIG.2.FIG.2is a schematic diagram showing a biological field effect sensing chip for detecting a testing sample according to the technology disclosed in the present invention. InFIG.2, when the testing sample90with a plurality of targets (or target molecules)902is placed in the detecting region, thereby the testing sample is allowed to fully contact the plurality of receptors60for a period time. During the reaction process, the plurality of receptors60on the upper conductive layer418is used to capture at least one of the plurality of targets (or target molecules)902in the testing sample90, after the plurality of receptors60captured the at least one of the plurality of targets (or target molecules)902, the voltage value is transmitted to the gate electrode202of the field effect transistor20through the upper conductive layer418, the plurality of second conductive plugs512, the intermediate conductive layer414and the plurality of first conductive plugs510, and then the gate electrode202of the field effect transistor20outputs the current value (Iout) which is corresponding to the voltage value to an external processing unit (not shown) to obtain the concentration value (or quantity) of the plurality of targets902in the testing sample90.

For example, the testing sample90includes a BTP buffer containing unknown target concentration, whole blood or plasma, in which when the testing sample90is whole blood or plasma, the testing sample90is diluted with BTP buffer solution. Next, the diluted testing sample90is dropped into the detecting region (that is, the second region10B of the substrate), the diluted testing sample90is allowed to stand for a period of time, so as to the plurality of receptors60is fully contacted the diluted testing sample90, so that the plurality of receptors60has enough time to capture at least one of the plurality of targets902in the diluted testing sample90. The voltage value of the upper conductive layer418will change with the number of the targets902in the diluted testing sample90captured by the plurality of receptors60, and the field effect transistor20will output the voltage value in the form of current (IoutinFIG.2) that is corresponding to the upper conductive layer418to the external processing unit (not shown) which is connected to the biological field effect sensing chip1, thereby, the external processing unit (not shown) is provided for processing the current change generated by the plurality of receptors60capturing the plurality of targets902in the diluted testing sample90, so the concentration value (or quantity) of the plurality of targets902in the testing sample90can be obtained. In this embodiment, the targets902in the testing sample90can be an organism. When the testing sample90is buffer solution, the targets902in the buffer solution includes yeast, bacteria, viruses or proteins. When the testing sample90is plasma, the targets902in the plasma is cell.

According to abovementioned, since the good air tightness between the bottom conductive layer410and the isolation layer30of the multilayer interconnect structure40disclosed in this invention, when the testing sample is plasma, whole blood or other testing sample in liquid state that is dropped into the opening302(the second region10B where the multilayer interconnect structure40is located). The testing sample90in liquid state is not overflowed between the bottom conductive layer410and the isolation layer30of the multilayer interconnect structure40and the short of the field effect transistor20is not induced, so that the durability of the biological field effect sensing chip1is improved. Accordingly, the multilayer interconnect structure40and the field effect transistor20are integrated on the substrate10to form the biological field effect sensing chip1which can achieve the purpose of the liquid detection on the chip.

The present invention also provides another embodiment of the biological field effect sensing chip2, which includes a substrate1000having a source region1002and a drain region1004therein, an isolation layer1040having an opening1042on the substrate10and the opening1042is used to expose the surface of the substrate1000, a gate oxide layer1010is disposed on the surface of the substrate1000, a gate electrode1012is disposed on the gate oxide layer1010, a multiplayer interconnect structure is arranged on the gate electrode1012, in which the multilayer interconnect structure includes a bottom conductive layer1022, the upper conductive layer1024, and a dielectric layer1030with a plurality of conductive plugs1030between the bottom conductive layer1022and the upper conductive layer1024, and the four sides of the upper conductive layer are embedded into the insulation layer1040to expose the portion of a surface of the upper conductive layer1024, a plurality of receptors1050is arranged on the exposed surface of the upper conductive layer1024to capture at least one of the plurality of targets (not shown) in a testing sample (not shown). It should be noted that where the region of the plurality of receptors1050is regarded as the detecting region. In this embodiment, the material, structure, and/or the function of the multilayer interconnect structure is same as the abovementioned inFIG.1andFIG.2, thus, it is not to describe repeatedly herein.

Next, please refer toFIG.4.FIG.4is a schematic diagram showing another embodiment of a biological field effect sensing chip detecting a testing sample according to the technology disclosed in the present invention. InFIG.4, when the testing sample1060with a plurality of targets (or target molecules)1062is dropped into the detecting region of the biological field effect sensing chip2, the testing sample1060is allowed to fully contact the plurality of receptors1050for a period of time. During the reaction process, the plurality of receptors1050on the surface of the upper conductive layer1024is used to capture the plurality of targets (or target molecules)1062in the testing sample1060. Similarly, after the plurality of receptors1050captured the at least one of the plurality of targets (or target molecules)1062in the testing sample1060, the voltage value is transmitted to the gate electrode1012through the upper conductive layer418, the plurality of conductive plugs1032and the bottom conductive layer1022and outputs the current value (Iout) which is corresponding to the voltage value to an external processing unit (not shown) through the drain region1004to obtain the concentration value (or quantity) of the plurality of targets1062in the testing sample1060.

In this invention, it should be noted that the four sides of the upper conductive layer1024of the multilayer interconnect structure are embedded into the isolation layer1040, thereby, there is no void or gap between the upper conductive layer1024and the isolation layer1040to obtain the good air tightness between the upper conductive layer1024and the isolation1024, so as to the biological field effect sensing chip2also has good air tightness to prevent the leakage or overflow when the testing sample1060is dropped into the biological field effect sensing chip2. In addition, the upper conductive layer1024can be regarded as an entire metal layer that is placed on the uppermost layer of the multilayer interconnect structure. Accordingly, when the plurality of receptors1050is fixed on the surface of the upper conductive layer1024can be formed by spin on method, so the more receptors1050are allowed to form on the upper conductive layer1024, and the shape of the upper conductive layer1024is not to be considered.