TW202300907A - Sensing chip with fluid device - Google Patents

Abstract

A sensing chip with fluid device is provided, which includes a substrate with a first area and a second area; a field effect transistor which is arranged in the second area of the substrate and is electrically connected with the field effect transistor. The fluid device includes an insulation layer with a window to expose the surface of the substrate in the second area. A second gate electrode is arranged in the window of the isolation layer on the second area of the substrate. The second gate electrode includes a polysilicon layer and one or more metal layer(s) thereon, and a reference electrode adjacent to the second gate on the second area of the substrate. The fluid to be tested is placed in the fluid device to contact with the second gate, and the receptor on the metal layer will capture the target in the fluid to be tested, so the voltage of the metal layer will change follow with the amount of the target which are captured by the receptor. Thus, the concentration of the target in the fluid can be obtained by the changes of the voltage of the metal layer.

Description

Sensing wafer with fluidic device

The invention relates to a detection technology field, in particular to a sensing chip capable of detecting proteins, bacteria, viruses and suspended particles and having a fluid device.

Biosensors are devices that sense and detect biomolecules based on electrical, electrochemical, optical, and mechanical detection principles. Biosensors with transistors can electrically sense charge, photon, and mechanical properties of biomolecules or bioentities. This detection action can be achieved through direct detection and sensing, or through the reaction or interaction of specific reactants with biomolecules/biological entities. These biosensors can be manufactured with semiconductor processes, can convert electronic signals quickly, and are easily applied to integrated circuits (integrated circuits; ICs) and microelectromechanical systems (microelectromechanical systems; MEMs).

A biochip is essentially a miniature laboratory that can carry out hundreds or thousands of biochemical reactions at the same time. Biochips can detect special biomolecules, measure their properties, calculate and process signals, and even analyze data directly. Therefore, biochips allow researchers to quickly screen a large number of biological analytes, and are used in everything from disease diagnosis to detection of biochemical terrorist attacks. various purposes. Advanced biochips utilize many biosensors alongside fluidic channels for reaction integration, sensing, and sample management. Bio-field-effect transistors (biological field-effect transistors, or bio-organic field-effect transistors; BioFET) are biosensors containing transistors that can sense biomolecules or biological entities electrically. Although biofield effect transistors have advantages in many aspects, there are also some challenges in their manufacture and/or operation, such as: based on issues of compatibility with semiconductor manufacturing processes, biological limitations and/or limits, in large There are many challenges in the large scale integration (LSI) process, such as the integration of electronic signals and biological applications.

In addition, the bio-sensing chip in the prior art can only detect the presence/absence of bacteria, viruses or suspended particles, and the detection area range is limited, and the concentration thereof cannot be estimated. In addition, the high-sensitivity nanowires designed in the wafer method are prone to noise interference, so that misjudgment is likely to occur, and the nanowires are exposed by polysilicon (polysilicon). This is a special process, but most Wafer factories are unwilling to provide special and customized processes to cooperate with production, so the yield rate cannot be improved, and effective production cannot be achieved.

Polymerase chain reaction (PCR, polymerase chain reaction) needs to provide a long detection reaction time or need to be labeled before it can be detected, and requires expensive instruments to operate, so it cannot be popularized.

The main purpose of the present invention is to disclose a sensing chip with a fluidic device, which can be designed according to the complementary metal oxide semiconductor (CMOS, complementary metal oxide semiconductor) process provided by the current chip factory.

Another object of the present invention is to use a sensing chip with a fluid device to detect the liquid or gas to be tested. In addition to quickly detecting whether the target in the fluid to be tested exists, it can also detect The concentration of the target substance in the fluid to be measured.

Another object of the present invention is to use the sensing chip with a fluid device to detect temperature-sensitive targets, and use the temperature control unit to provide a temperature control signal to the sensing chip with a fluid device for sensing the sensor with a fluid device The fluid to be tested on the chip is heated and its temperature is regulated, so that the target in the fluid to be tested increases its kinetic energy or changes and decomposes due to the increase in temperature. The receptor on the metal layer can effectively capture the target. The voltage value change generated by the layer is used to measure the quantity or concentration change of the target substance in the fluid to be measured at a preset temperature.

Another object of the present invention is to form a sensing element with a plurality of sensing wafers with fluidic devices in a subdivided detection manner, so as to improve detection accuracy by increasing the sample volume of the fluid to be measured.

Another object of the present invention is to use multiple sensing chips with fluidic devices to form a sensing element, according to whether the material of the receptors in the sensing chips with fluidic devices is the same or different, so as to capture the flow in the same fluid to be measured. The same target object or multiple different target objects in the body can save detection time, and the detection results of one or more target objects can be obtained to provide subsequent judgment or evaluation.

According to the above purpose, the present invention discloses a sensing chip with a fluid device, comprising: a substrate having a first region and a second region; a field effect transistor disposed in the first region of the substrate, and the field effect transistor includes: The first gate, the source and the drain, and the first gate is arranged on the source and the drain; and the fluid device is arranged on the second area of the substrate and is electrically connected with the field effect transistor, wherein the fluid device includes : The isolation layer has a window to expose the surface of the substrate in the second region, wherein the area surrounded by the window is an accommodation space; the second gate is arranged in the window of the isolation layer, and the second gate is upwardly supported by the substrate The sequence includes a polysilicon layer and one or more layers of metal layers; and a reference electrode, which is disposed on the second region of the substrate adjacent to the second gate, wherein the fluid to be measured is accommodated in the accommodation space, so that the second gate After contacting the fluid to be tested, multiple receptors on the metal layer are used to capture multiple targets in the fluid to be tested, and the voltage value of the metal layer of the second gate will follow these receptors to capture these targets and the second gate transmits the change of the voltage value of the metal layer to the external processing unit through the field effect transistor to process the change of the voltage value to calculate the concentration of the target substance.

In a preferred embodiment of the present invention, the reference electrode is when the fluid to be measured is accommodated in the accommodating space, it is in contact with the fluid to be measured and supplies the voltage required to measure the change in the voltage value of the metal layer of the second gate. .

The present invention discloses another sensing chip with a fluid device, comprising: a substrate having a first region and a second region; a field effect transistor disposed in the first region of the substrate, the field effect transistor including a first gate, The source and the drain, the first gate is arranged between the source and the drain and on the substrate; and the fluid device is arranged on the second area of the substrate and is electrically connected with the field effect transistor, the fluid device includes: an isolation layer, has a window and exposes the surface of the substrate in the second area, wherein the area surrounded by the window is an accommodation space; the second gate is arranged in the window of the isolation layer, and the second gate includes a polysilicon layer from the substrate upwards and one or more layers of metal layers; and a reference electrode, adjacent to the second gate and disposed on the second region of the substrate, the reference electrode is in contact with the fluid to be measured, wherein the fluid to be measured is accommodated in the accommodating space, The metal layer of the second gate is in contact with the fluid to be measured, one end of the polysilicon layer in the second gate is used for grounding and the other end of the polysilicon layer is electrically connected to the temperature control unit, and the temperature control unit provides a temperature control signal, And through the polysilicon layer, the temperature control signal is used to heat the fluid to be measured in the accommodating space and regulate its temperature, so that when the temperature of the fluid to be measured reaches the preset temperature, multiple receiving points on the surface of the metal layer The detector is used to capture multiple targets in the fluid to be measured, and the voltage value of the metal layer of the second gate will change with the number of targets captured by multiple receptors, and the second gate will metal layer The change in the voltage value of the field effect transistor is transmitted to the external processing unit with the corresponding change in the current value, and is processed by the external processing unit to obtain the preset temperature of the multiple targets in the fluid to be measured corresponding to the change in the voltage value of the metal layer. The lower concentration value.

In a preferred embodiment of the present invention, the temperature regulation unit is a pulse width modulation unit (PWM, pulse width modulation).

In a preferred embodiment of the present invention, the preset temperature range is 50°C-95°C.

According to the above purpose, the present invention also discloses another sensing chip with a fluid device, comprising: a substrate having a first region and a second region; a field effect transistor disposed in the first region of the substrate, the field effect transistor comprising The first gate, the source and the drain, and the first gate is arranged on the source and the drain; and the fluid device is arranged on the second area of the substrate and is electrically connected with the field effect transistor, wherein the fluid device includes: The isolation layer has a window and is arranged on the second area of the substrate to expose the surface of the substrate in the second area, wherein the area surrounded by the window is an accommodation space; the second gate is arranged in the window of the isolation layer , the second gate includes a polysilicon layer and one or more layers of metal layers from the substrate upwards, thereby, when the sensing chip with the fluidic device is placed in an environment with the fluid to be measured, and the fluid to be measured passes through the fluidic device When a voltage is applied to the second gate polysilicon layer of the fluidic device, multiple charges will be generated on the metal layer of the second gate and the surface of the receiver, and each charge on the metal layer is used to capture the The target in the fluid to be measured, and the voltage value of the metal layer of the second gate will change with the number of these charge-captured targets, and the second gate will transmit the voltage value change of the metal layer through the field effect transistor To the external processing unit for processing, and further calculation to obtain the target concentration in the liquid to be tested.

In a preferred embodiment of the present invention, the charge can be positive charge or negative charge.

In a preferred embodiment of the present invention, the constant voltage applied to the second gate is less than 30 volts.

In a preferred embodiment of the present invention, the fluid to be measured is gas.

In a preferred embodiment of the present invention, the target object may be bacteria, virus, suspended particles or gas molecules.

First, please refer to Figure 1A. FIG. 1 shows a schematic structural view of a sensing wafer with a fluidic device. In FIG. 1A , a sensing chip 1 with a fluid device is composed of a field effect transistor (Field effect transistor; FET) 20 and a fluid device. The sensor chip 1 with a fluidic device includes a substrate 10, on which a dotted line is provided to distinguish a first region 10A and a second region 10B, where the substrate 10 is divided into a first region 10A and a second region 10B For easy understanding of the subsequent description, there will be no dotted lines on the actual substrate 10 . In the first region 10A of the substrate 10, a field effect transistor 20 is provided. The field effect transistor 20 is, for example, an N-type metal oxide semiconductor (NMOS), and its structure at least includes a gate 202, a source 204, and a drain 206. The gate 202 is interposed between the source 204 and the drain 206 and is disposed on the substrate 10 , the source 204 and the drain 206 are disposed in the first region 10A of the substrate 10 , and the first region 10A of the substrate 10 is also provided with An isolation layer (or may be called a field oxide layer) 30 . It should be noted that the isolation layer 30, the gate 202, the source 204 and the drain 206 are formed by using a suitable complementary metal oxide semiconductor (CMOS) process, and the formation steps are not the main technical features of the present invention and are not described here. Make more statements.

The fluidic device is disposed on the second region 10B of the substrate 10 and is electrically connected to the field effect transistor 20 , wherein the fluidic device includes: an isolation layer 30 , a second gate 40 and a reference electrode 50 . The isolation layer 30 has a window 302 for exposing the surface of the substrate 10 in the second area 10B, and the area surrounded by the window 302 is an accommodating space. The second gate 40 is disposed in the window 302 of the isolation layer 30 , and the polysilicon layer 402 and one or more layers of metal layers 404 are sequentially upward from the substrate 10 . A plurality of receptors 406 are also disposed on the metal layer 404 . In addition, a reference electrode (reference electrode) 50 is provided on the second region 10B adjacent to the second gate 40 and disposed on the substrate 10. The reference electrode 50 is in contact with the fluid to be measured 60 and supplies the second gate for measuring. The voltage required when the voltage value of the metal layer 404 of the electrode 40 changes.

In this embodiment, the area surrounded by the window 302 of the isolation layer 30 on the second area 10B is used as an accommodating space for accommodating the fluid 60 to be measured (as shown in FIG. 1B ), so when the fluid 60 to be measured is placed After the accommodating space 302, let the fluid 60 to be tested contact the metal layer 404 of the second gate 40 for a period of time, observe the voltage value of the metal layer 404 to change, and judge the fluid 60 to be tested by the change of the voltage value Whether there is a target object 602 and the concentration of the target object 602 in it, the detailed operation will be described later.

Then please refer to FIG. 1B . FIG. 1B shows a schematic circuit diagram of a sensing wafer with a fluidic device. In FIG. 1B , the source 204 of the field effect transistor 20 is grounded (GND), and the drain 206 is electrically connected to an external processing unit (not shown in the figure). During operation, the fluid to be measured 60 is placed in After having the accommodating space 302 of the sensing wafer 1 with the fluidic device, allow the fluid to be measured 60 to contact a plurality of receptors (receptors) 406 on the metal layer 404 of the second gate electrode 40 of the fluidic device and let stand for at least 30 minutes , during the standing process, these receptors (receptors) 406 are used to capture the target (or target molecule) 602 in the fluid 60 to be measured. It should be noted that the receptors 406 are produced after the sensing wafer 1 The antibody is immobilized on the metal layer 404 during processing.

For example, the fluid 60 to be tested can be BTP buffer, whole blood or plasma containing an unknown target concentration, wherein when the fluid 60 to be tested is whole blood or plasma, the BTP buffer can be used to The fluid to be tested 60 is diluted, and then the diluted fluid to be tested 60 is placed in the accommodating space 302 (as shown in FIG. Stand still for a period of time, this rest time is in addition to allowing the metal layer 404 of the second gate 40 to have enough contact time with the diluted fluid 60 to be measured, so that the receptor 406 on the metal layer 404 can have enough time Capture the target object 602 in the diluted fluid 60 to be measured. When the multiple receptors 406 on the surface of the metal layer 404 of the second gate 40 capture the target object 602 in the diluted fluid 60 to be measured, the metal layer The voltage value of 404 will change with the number of target objects 602 captured by the receiver 406, and then output the changed current value of the metal layer 404 of the second gate 40 through the field effect transistor 20 (that is, in FIG. 1B I _out ) to an external processing unit (not shown in the figure) for processing to obtain the concentration value (or quantity) of the diluted target object 602 in the fluid to be measured 60 corresponding to the voltage value of the metal layer 404 . In this embodiment, the target object 602 in the fluid to be tested 60 may be a living organism, and when the fluid to be tested 60 is a buffer, the target object 602 in the buffer may be yeast, bacteria, virus or protein and when The fluid 60 to be tested is plasma, and the target object 602 in the plasma may be cells.

Next, please refer to Figure 2. FIG. 2 is a schematic diagram showing yet another implementation of the sensing chip with fluidic devices disclosed in the present invention. In FIG. 2 , the structures, connection relationships and functions of the components of the sensing chip 1 with fluidic devices are the same as those in FIG. 1A and FIG. 1B , and will not be further described here. The difference between FIG. 2 and the aforementioned FIG. 1A and FIG. 1B is that one end of the polysilicon layer 402 in the second gate 40 is used for grounding (GND) (ie, the left side of FIG. 2 ) and the other end of the polysilicon layer 402 is used for the temperature control unit. 15 is electrically connected and the sensing chip 1 with the fluid device is electrically connected with the temperature sensing circuit 17 . In this embodiment, the temperature sensing circuit 17 is used to measure the temperature of the sensor chip 1 having a fluid device, and the temperature control unit 15 is used to provide a temperature control signal, and the width of the temperature control signal is used to control the polysilicon layer 402 temperature, thereby heating the fluid to be measured 60 in the accommodating space, since the target object 602 in the fluid to be measured 60 increases the kinetic energy in the fluid to be measured 60 due to the increase in temperature, making the target object 602 easier to be detected Captured by the receptor 406 on the metal layer 404, the detailed detection steps are as follows. In addition, the connection positions of the polysilicon layer 402 and the grounding and temperature control unit 15 shown in FIG. 2 can be interchanged left and right.

Firstly, the fluid to be tested 60 is placed in the sensing wafer 1 of the fluid device, specifically, the fluid to be tested 60 is dropped into the accommodating space. Next, the temperature control unit 15 provides a temperature control signal to heat the fluid to be measured through the polysilicon layer 402, and regulates the temperature of the polysilicon layer 402 with the width of the temperature control signal, thereby further controlling the temperature of the fluid to be measured 60, so that the fluid to be measured The temperature of the fluid 60 may reach a preset temperature after a period of heating, wherein the preset temperature ranges from 50°C to 95°C. In another embodiment, if the biological detection is carried out, since the biological target may be destroyed due to the high temperature, the preset temperature is 90°C when the biological detection is carried out, and the preferred temperature is less than 90°C. ℃.

It should be noted that the temperature control unit 15 provides a temperature control signal, and controls its width to pass through the polysilicon layer 402 to heat the fluid 60 to be measured. At the same time, the temperature sensing circuit 17 continuously measures the temperature of the entire sensing chip 1 for Control the temperature of the fluid to be tested 60 and the sensing chip 1 with the fluidic device at a fixed temperature, whereby the fluid to be tested 60 can be measured during the process of heating the fluid to be tested to a preset temperature The concentration or quantity of the target object 602. Specifically, when the temperature control unit 15 is used to heat the fluid 60 to be tested, the target object 602 in the fluid to be tested 60 will have a change in kinetic energy due to the temperature rise, and this change in kinetic energy will drive the target object 602 to Movement or decomposition in the test fluid 60 is more easily captured by the plurality of receptors 406 on the surface of the metal layer 404. 1A and 1B, in the heating process, the voltage value of the metal layer 404 of the second gate 40 will change with the number of objects 602 captured by the plurality of receptors 406, and the second The gate 40 transmits the change of the voltage value of the metal layer 404 to the external processing unit (not shown in the figure) through the field effect transistor with the corresponding change of the current value, and is processed by the external processing unit (not shown in the figure) until After the temperature of the fluid to be tested 60 reaches the preset temperature, and the current value does not change any more, a plurality of voltages in the fluid to be tested 60 corresponding to the change of the voltage value of the metal layer 404 at the preset temperature can be obtained. The concentration value of the target object 602 .

In the above-mentioned embodiments of FIG. 1A , FIG. 1B and FIG. 2 , besides the above-mentioned whole blood or plasma, the fluid 60 to be tested can also be a BTP buffer containing an unknown concentration of the target substance. In addition, the metal layer 404 in the second gate 40 can be one layer or multiple layers, and the material of the metal layer 404 and the reference electrode 50 can be aluminum-copper alloy (Al—Cu).

According to the above, it can be obtained that the sensing chip 1 with a fluid device disclosed in the present invention can detect the concentration of the target object 602 in the fluid 60 to be measured, but in order to avoid the excessive amount of the target object 602 in the fluid 60 to be measured, it is easy to The error is caused by insufficient output of the field effect transistor 20 . Therefore, in order to improve the accuracy, the present invention also discloses another sensing chip 1000 with a fluidic device, as shown in FIG. 3A . 3A is a top view of another embodiment of a sensing wafer with multiple fluidic devices. In FIG. 3A, the sensing chip 1000 is also composed of a fluid device and a field effect transistor 20. The difference from the aforementioned sensing chip 1 is that the fluid device of the sensing chip 1000 in this embodiment also has isolation layer (not shown in the figure), the second gate 4000 and a reference electrode (not shown in the figure). The second gate 4000 is also disposed in an isolation layer with a window (not shown in the figure). The second gate 4000 upward from the substrate is a polysilicon layer 4002 and one or more layers of metal layers 4004 in sequence. In this embodiment, the polysilicon layer 4002 in the second gate 4000 is a continuous whole layer, but the metal layer 4004 is arranged on the polysilicon layer 4002 in a subdivided manner, and each metal layer 4004 is connected with a field effect electric current. The crystals 20 are electrically connected, and the field effect transistors 20 then connect these output currents in parallel to calculate the variation of the total output current.

In another embodiment, there are a plurality of sensing chips 1000 on one sensing element, and each sensing chip 1000 is also composed of a fluid device and a field effect transistor 20, and the fluid device is composed of an isolation layer (not shown in the figure) indicated), a reference electrode (not shown in the figure) and a second gate 4000, wherein the second gate 4000 is composed of one layer of polysilicon layer 4002 and one or more layers of metal layer 4004, that is, one layer of polysilicon layer 4002 corresponds to One or more layers of metal layer 4004 , the second gate 4000 of each fluid sensing device of the wafer 1000 is used to capture and further detect the target object 602 of the fluid 60 to be measured. With the sensing chip 1000 having two second gates 4000 with different structural designs, the fluid 60 to be measured with a large number of targets 602 can be divided into small areas by the second gates 4000 of several sensing elements. mode detection. Similarly, each second gate 4000 in the sensing chip 1000 with a fluidic device is electrically connected to a field effect transistor 20, so that when each second gate 4000 in the sensing chip 1000 with a fluidic device After contacting the fluid 60 to be tested, the voltage value change generated by the metal layer 404 of the second gate 4000 will output current to an external processing unit (not shown in the figure) through the field effect transistor 20 connected to the fluid device, and then Calculate the change in total output current in parallel. By means of such sub-area detection, it is judged whether there is a target object 602 in the fluid 60 to be tested in each sub-area, and at the same time, the concentration of the target object 602 in the fluid 60 to be measured in a sub-area can be obtained, and The sum of the concentration targets 602 per unit area is the sum of the targets 602 of the entire fluid 60 to be measured. Accordingly, the sensing elements with a plurality of sensing chips 1000 with fluidic devices can be detected in sub-districts. And the output parallel mode improves the sensitivity of the detection, and at the same time increases the corresponding sample volume of the fluid 60 to be tested and increases the accuracy of the detection result.

Next, please refer to FIG. 3B . FIG. 3B shows that there are multiple sensing chips in the sensing element, and the multiple sensing chips detect different targets in the same fluid to be measured in a partitioned manner. In FIG. 3B, the structure of the sensing element is the same as that of FIG. 3A, except that the sensing chip on the sensing element is divided into four blocks: Test A, Test B, Test C, and Test D. In the block, the receptors 4006 on the second gate 4000 of the fluidic device of the sensing wafer on the same block are the same, but the receptors in different blocks are different, so Test A, Test B, Test C and Test D The receivers in the four blocks are respectively 4006A, 4006B, 4006C and 4006D. In this embodiment, the purpose of dividing into different blocks is to capture different targets 602A, 602B, 602C and 602D in the same fluid 60 to be tested. Therefore, similarly, the fluid 60 to be tested is accommodated in the accommodating space 302 of the sensing chip 1 with the fluidic device in the above-mentioned FIG. 1A and FIG. The receptors 4006A, 4006B, 4006C and 4006D in Test D are different, so the targets 602A, 602B, 602C and 602D to be captured in the fluid 60 to be tested are also different. Therefore, the above-mentioned sensing chip can be arranged on the metal layer 4004 of the second gate 4000 in each block Test A, Test B, Test C and Test D according to the target object 602 to be detected by the user. different types of receivers 4006A, 4006B, 4006C, and 4006D. Accordingly, different targets 602A, 602B, 602C, and 602D can be captured from the same fluid 60 to be tested at the same detection time, which can greatly save The user's operating time and manpower.

Next, please refer to FIG. 4A . FIG. 4A is a schematic diagram showing another implementation of the sensing wafer with fluidic devices disclosed in the present invention. In FIG. 4A, the sensing chip 7 with the fluidic device is also composed of the field effect transistor 20 and the fluidic device 80. The sensing chip 7 with the fluidic device includes a substrate 70, and a dotted line is arranged on the substrate 70 for the area. It is divided into a first region 70A and a second region 70B. In the first region 70A of the substrate 70, a field effect transistor 20, such as an N-type metal oxide semiconductor (NMOS), is provided, and its structure and formation method are the same as those in FIG. To add to the statement. An isolation layer 30 is disposed on the second region 70B of the substrate 70 , and the isolation layer 30 has a window 302 for exposing the surface of the substrate 10 in the second region 10B.

The fluidic device is disposed on the second region 70B of the substrate 70 and is electrically connected to the field effect transistor 20 , wherein the fluidic device includes: an isolation layer 30 and a second gate 80 . The isolation layer 30 has a window 302 for exposing the surface of the substrate 70 in the second region 70B, and the region surrounded by the window 302 is an accommodating space. The second gate 80 is disposed in the window 302 of the isolation layer 30 , and the second gate 80 is composed of a polysilicon layer 802 and one or more layers of metal layers 804 from the substrate 70 upwards.

In this embodiment, the area surrounded by the window 302 of the isolation layer 30 is used as an accommodating space, and this accommodating space is used to accommodate the fluid 90 to be measured (as shown in FIG. 2B ), so when the fluid 90 to be measured is contained After being placed in the accommodating space 302 , the fluid 90 to be tested will contact the metal layer 804 of the second gate 80 , so that the voltage value of the metal layer 804 changes. The detailed operation will be described later. The fluid 90 to be measured in this embodiment is gas.

Then please refer to FIG. 4B . FIG. 4B shows a schematic circuit diagram of a sensing chip with a fluidic device. In FIG. 4B , the source 204 of the field effect transistor 20 is connected to the ground, and the drain 206 is connected to an external processing unit (not shown in the figure). When operating, the sensing chip 7 with the fluid device is placed in the environment with the fluid 90 to be measured, and after standing for a period of time, a voltage is applied to the second gate 80, and the voltage value is less than 30 volts (V). , the preferred voltage range may be 5-7 volts. Specifically, when the voltage applied to the polysilicon layer 802 of the second gate 80 is a positive voltage, a plurality of negative charges opposite to those of the polysilicon layer 802 will be generated on the surface of the metal layer 804 of the second gate 80. 8042, and these negative charges 8042 will be affected by positively charged bacteria, viruses, aerosols or gas molecules in the fluid 90 to be tested; similarly, if the polysilicon layer 802 applied to the second gate 80 is If the negative voltage is applied, a plurality of positive charges (not shown in the figure) that are electrically opposite to the polarity of the polysilicon layer 802 will be generated on the surface of the metal layer 804 of the second gate 80, and these positive charges 8042 will be detected by the fluid 90 Negatively charged bacteria, viruses, aerosols or gas molecules affect the charge.

For example, when a positive voltage (V _in ) is applied to the polysilicon layer 802 of the second gate 80, a plurality of negative charges 8042 will be generated on the surface of the metal layer 804 of the second gate 80 and the receptor 806, and these negative charges The 8042 will be affected by the positively charged target 902 in the fluid 90 to be tested, such as bacteria, viruses, suspended particles or gas molecules, and the voltage value of the metal layer 804 of the second gate 80 will follow the voltage value of the metal layer 804 These targets 902 on the surface are changed, and then the current value generated by the metal layer 804 of the second gate 80 is transmitted to the external processing unit (not shown in the figure) through the field effect transistor 20, and the current value corresponding to the metal layer can be obtained. The voltage value at 804 is the concentration value (or quantity) of the target object 902 in the fluid 90 to be measured.

In another embodiment, if it is to obtain the concentration of various target objects 902 in the fluid 90 to be tested per unit volume, these target objects 902 can be bacteria, viruses, suspended particles or gas molecules, corresponding to each different The object 902 is used to change the receptor 806 in the second gate 80 of the sensing wafer 7 with a fluidic device. Representation) is placed in the detection environment with the fluid 90 to be measured, and a voltage is applied to the second gate 80 of each sensing chip 7 with a fluidic device, each of the second gates 80 of the sensing chip 7 with a fluidic device Negative charges (or positive charges) will be generated on the surface of the metal layer 804, and various target objects 902 in the fluid 90 to be measured will be captured according to the characteristics of each receptor 806, and then output to the external processing unit (not shown) through the field effect transistor 20 shown in the figure), thereby the concentration of various target objects 902 in the fluid 90 to be tested can be obtained.

Please refer to Figure 5 next. FIG. 5 is a flowchart showing the steps of detecting a sensing wafer with a fluidic device according to the technology disclosed in the present invention. While illustrating the schematic flow chart of the steps in FIG. 5 , the sensing wafer 1 with the fluidic device shown in FIGS. 1A-1B is used as an example for illustration. In FIG. 5 , step S10 : providing a sensing wafer with a fluidic device. Step S12: cleaning the sensing wafer with the fluidic device. In this step, the sensing wafer 1 with the fluidic device is cleaned with deionized water to remove some impurities on the sensing wafer 1 with the fluidic device, so as to avoid generating impurities when detecting the fluid 60 to be measured. The information will affect the accuracy of the test results.

Next, step S14: immersing the sensing chip with the fluidic device in a buffer solution to measure a base line. In this step, first soak the sensing chip 1 with the fluidic device in the buffer solution. Since there is no target in the buffer solution, the metal layer 404 of the second gate 40 of the sensing chip 1 with the fluidic device The surface and the receptor 406 will not affect the voltage, but the voltage value of the sensing chip 1 with the fluidic device after soaking in the buffer solution can be supplied by the reference electrode 50, and the voltage value is transmitted to the external processing device (not in the The voltage value shown in the figure), this voltage value is the voltage value of the voltage provided by the reference electrode to the metal layer 404 itself through the buffer solution, and the baseline (baseline) of the drain current and the gate voltage is obtained, and this baseline can be used for It is compared with the fluid to be tested that has the target object in the subsequent detection.

In step 16: the fluid to be tested is accommodated in the sensing chip with the fluid device, and is left to stand for 30 minutes before cleaning and testing. In this step, the fluid 60 to be measured is accommodated in the sensing wafer 1 with a fluidic device, and left to stand for 30 minutes, so that the fluid 60 to be measured can be connected to the second gate 40 of the sensing wafer 1 with a fluidic device. Metal layer 404 is substantially in contact. During the standing process, the receptor 406 on the surface of the metal layer 404 is used to capture the target object 602 in the fluid 60 to be measured. As mentioned above, after the receptor 406 captures the target object 602 , the voltage value of the metal layer 404 in step 20 will be changed.

Next, step S18 : cleaning the sensing chip with the fluidic device with a buffer solution. In this step, the sensing wafer 1 with fluidic device soaked in the buffer solution in the previous step 18 is cleaned with a new buffer solution. For detection accuracy, the sensing wafer 1 with fluidic device needs to be cleaned.

Step 20: Repeat step 14 to compare the detection result with the original baseline to determine whether there is a target object in the fluid to be tested and the concentration of the target object. In this step, the detection result obtained in the aforementioned step 14 is compared with the baseline. In addition to judging whether there is the target object 602 in the fluid 60 to be tested by the change of the voltage value, it is also possible to use the voltage The voltage value is used to estimate the concentration of the target object 602 in the fluid 60 to be tested.

Based on the above steps, FIG. 6 is a schematic diagram showing the comparison between the reference line and the fluid to be tested containing three different concentrations of Escherichia coli. In Figure 5, the baseline was obtained using a buffer solution. Then, according to the above steps 18 to 20, the fluids to be tested with different concentrations of Escherichia coli were contained in the sensing chip 1 with a fluid device for detection, wherein the concentrations of Escherichia coli were 10 ² cells/ml, 10 cells/ml, respectively. ⁴ /cells/ml and 10 ⁶ cells/ml. From Fig. 4, except that the sensing chip 1 with the fluidic device can detect Escherichia coli in the fluid to be tested, it can also be obtained that under the same voltage condition, the higher the concentration of different Escherichia coli, the more sensitive the fluidic device is. The change of the current value of the metal layer 404 of the second gate electrode 40 of the wafer 1 is also different.

To sum up the above, the sensing chip 1, 7, 1000 with a fluidic device disclosed in the present invention can not only detect the fluid to be tested in the form of liquid or gas, but also detect the target object 602, 602A, 602B of the fluid to be tested 60 , 602C, 602D concentration is not just to detect the existence of target objects 602, 602A, 602B, 602C, 602D, but can obtain the target objects 602, 602A, 602B, 602C in the fluid to be tested in a short time , 602D concentration, and the obtained results can be provided to follow-up relevant personnel for research or judgment, so as to solve the technical problem that the sensing chip in the prior art can only detect the existence of the target object, but cannot quantify the target object .

In addition, in the embodiment of the present invention, the second gates 40, 80, 4000 in the sensing chips 1, 7, 1000 with fluidic devices are compatible with the current standard CMOS (complementary metal oxide semiconductor) semiconductor process, Therefore, the chip factory can complete the process without additional special or customized process, which solves the technical problem in the prior art that the sensing chip requires a special process to be completed.

1. 1000: Sensing wafer with fluidic device 10: Substrate 10A: The first area 10B: Second area 15: Temperature control unit 17: Temperature sensing circuit 20: field effect transistor 202: Gate 204: source 206: drain 30: isolation layer 302: window 40, 4000: second gate 402, 4002: polysilicon layer 404, 4004: One or more metal layers 406, 4006, 4006A, 4006B, 4006C, 4006D: Receiver 50: Reference electrode 60: fluid to be tested 602, 602A, 602B, 602C, 602D: objects 7: Sensing Wafer with Fluidic Devices 70: Substrate 70A: The first area 70B: Second area 80:Second gate 802: polysilicon layer 804: One or more metal layers 804: 2 charges 806: Receiver 90: Fluid to be tested 902: Target Test A, Test B, Test C, Test D: blocks Step S10-Step S20: Flowchart of the steps when the sensing wafer with the fluidic device detects the liquid to be tested

FIG. 1A is a schematic diagram illustrating an embodiment of a sensing chip with fluidic devices according to the techniques disclosed in the present invention. FIG. 1B is a schematic circuit diagram showing a sensing chip with a fluidic device according to the technology disclosed in the present invention. FIG. 2 is a schematic circuit diagram showing yet another embodiment of a sensing chip with a fluidic device according to the technology disclosed in the present invention. 3A is a top view illustrating another embodiment of a sensing wafer with multiple fluidic devices according to the techniques disclosed herein. 3B is a top view showing that there are multiple sensing chips in the sensing element and the multiple sensing chips detect different targets in the same fluid to be measured in a partitioned manner according to the technology disclosed in the present invention. FIG. 4A is a schematic diagram illustrating another implementation of the sensing chip with fluidic devices disclosed in the present invention according to the technology disclosed in the present invention. 4B is a schematic circuit diagram showing a sensing chip with a fluidic device according to the technology disclosed in the present invention. FIG. 5 is a schematic flow diagram showing the steps of detecting a target object in a fluid to be measured by a sensing chip with a fluidic device according to the technology disclosed in the present invention. FIG. 6 is a schematic diagram showing a sensing chip with a fluidic device detecting fluid to be tested with E. coli according to the technology disclosed in the present invention.

1: Sensing wafer with fluidic device

10: Substrate

10A: The first area

10B: Second area

20: field effect transistor

202: Gate

204: source

206: drain

30: isolation layer

302: window

40:Second gate

402: polysilicon layer

404: One or more metal layers

406: Receiver

50: Reference electrode

60: fluid to be tested

602: Target

Claims (10)

A sensing wafer with a fluidic device, comprising: a substrate having a first region and a second region; A field effect transistor disposed in the first region of the substrate, the field effect transistor comprising a first gate, a source and a drain, the first gate disposed on the source and the drain between and on the substrate; and A fluid device, disposed on the second region of the substrate and electrically connected to the field effect transistor, the fluid device includes: an isolation layer having a window and exposing a surface of the substrate of the second region, wherein an area surrounded by the window is an accommodating space; a second gate disposed in the window of the isolation layer, the second gate comprising a polysilicon layer and one or more metal layers upward from the substrate; and a reference electrode, adjacent to the second gate and disposed on the second region of the substrate, the reference electrode is in contact with the fluid to be measured, Wherein, a fluid to be measured is accommodated in the accommodating space, so that after the metal layer of the second gate contacts the fluid to be measured, a plurality of receptors on a surface of the metal layer are used to catch the fluid A plurality of targets in the fluid to be measured, and a voltage value of the metal layer of the second gate will change with the number of targets captured by the receptors, and the second gate will The change in the voltage value of the metal layer is transmitted to an external processing unit through the field effect transistor with a corresponding change in the current value, and is processed by the external processing unit to obtain the current to be measured corresponding to the change in the voltage value of the metal layer. A concentration value of the target substances in the body. A sensing wafer with a fluidic device, comprising: a substrate having a first region and a second region; A field effect transistor disposed in the first region of the substrate, the field effect transistor comprising a first gate, a source and a drain, the first gate disposed on the source and the drain between and on the substrate; and A fluid device, disposed on the second region of the substrate and electrically connected to the field effect transistor, the fluid device includes: an isolation layer having a window and exposing a surface of the substrate of the second region, wherein an area surrounded by the window is an accommodating space; a second gate disposed in the window of the isolation layer, the second gate comprising a polysilicon layer and one or more layers of a metal layer upward from the substrate; and a reference electrode, adjacent to the second gate and disposed on the second region of the substrate, the reference electrode is in contact with the fluid to be measured, Wherein, a fluid to be measured is accommodated in the accommodating space, so that the metal layer of the second gate contacts the fluid to be measured, and one end of the polysilicon layer in the second gate is used for grounding and The other end of the polysilicon layer is electrically connected to a temperature control unit, the temperature control unit provides a temperature control signal, and uses the temperature control signal to heat the fluid to be measured in the accommodating space through the polysilicon layer and Regulating a temperature of the fluid to be tested so that the temperature of the fluid to be tested reaches a preset temperature, and a plurality of receptors on a surface of the metal layer are used to capture multiple fluids in the fluid to be tested. target, and a voltage value of the metal layer of the second gate will change with the number of the targets captured by the receptors, and the voltage value of the metal layer of the second gate will change A corresponding change in the current value is transmitted to an external processing unit through the field effect transistor, and is processed by the external processing unit to obtain the target objects in the fluid to be measured corresponding to the change in the voltage value of the metal layer. A concentration value at the preset temperature. The sensing wafer with fluidic device as described in claim item 1 or 2, wherein the reference electrode is in contact with the fluid to be measured, and is used to provide the voltage value change required for measuring the metal layer of the second gate electrode of a voltage. The sensing chip with a fluidic device as claimed in claim 2, wherein the temperature regulation unit is a pulse width modulation unit (PWM, pulse width modulation). The sensor chip with fluidic device as claimed in claim 2, wherein the preset temperature range is 50°C-95°C. A sensing wafer with a fluidic device, comprising: a substrate having a first region and a second region; A field effect transistor disposed in the first region of the substrate, the field effect transistor comprising a first gate, a source and a drain, the first gate disposed on the source and the drain between and on the substrate; A fluid device, disposed on the second region of the substrate and electrically connected to the field effect transistor, the fluid device includes: An isolation layer has a window and is disposed on the second region of the substrate to expose a surface of the substrate in the second region, wherein a region surrounded by the window is an accommodating space; and a second gate disposed in the window of the isolation layer, the second gate includes a polysilicon layer and one or more metal layers from the substrate upwards, Thus, when the sensing chip with the fluidic device is placed in an environment with a fluid to be measured, and the fluid to be measured passes through the second gate of the fluidic device, after standing still, the fluid When a voltage is applied to the second gate of the device, a plurality of charges will be generated on the surface of the metal layer of the second gate, and the charge of each charge on the metal layer will be released in the fluid to be measured. Influenced by a target object, and a voltage value of the metal layer of the second gate will change with the amount of the charges capturing the targets, and the voltage value of the metal layer of the second gate will be The voltage and current value is transmitted to an external processing unit through the field effect transistor to process the voltage and current value. The sensing chip with a fluidic device as described in claim 6, wherein the sensing element detects each of the sensing chips with the fluidic device in sub-districts and connects the output currents in parallel to calculate the change of the total output current value. The sensing wafer with fluidic device of claim 6, wherein the voltage is less than 30 volts. The sensing wafer with a fluid device as claimed in claim 6, wherein the fluid to be measured is gas. The sensing wafer with a fluidic device as claimed in claim 6, wherein the target object can be bacteria, virus, aerosol or gas molecule.

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