TWI834132B - 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 chip with fluidic device

The present invention relates to the field of detection technology, and in particular to a sensing chip that can detect proteins, bacteria, viruses, and suspended particles and has a fluid device.

Biosensors are devices that operate based on 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 using semiconductor processes, which can quickly convert electronic signals and can be easily applied to integrated circuits (ICs) and microelectromechanical systems (MEMs).

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

In addition, the existing biosensing chips can only detect the presence/absence of bacteria, viruses or suspended particles, and the detection area range is limited, and their concentration cannot be estimated. In addition, the high-sensitivity nanowires designed in the chip method are prone to noise interference, which may lead to misjudgment. Moreover, the nanowires are exposed with polysilicon. This is a special manufacturing process. However, most Chip factories are unwilling to provide special and customized processes to coordinate production and manufacturing, so they cannot improve yield and cannot produce efficiently.

In addition, polymerase chain reaction (PCR) requires a long detection reaction time or needs to be labeled before it can be detected. It also requires expensive equipment to operate and cannot be popularized.

The main purpose of the present invention is to disclose a sensing chip with a fluid device. The sensing chip with the fluid device can be designed based on the complementary metal oxide semiconductor (CMOS) process currently provided by chip factories.

Another object of the present invention is to use a sensing chip with a fluid device to detect liquid or gas fluid to be measured. In addition to quickly detecting whether the target object in the fluid to be measured 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 a sensing chip with a fluid device to detect a temperature-sensitive target, and use a temperature control unit to provide a temperature control signal to the sensing chip with a fluid device, so as to sense the fluid device. The fluid to be measured on the chip is heated and its temperature is adjusted, so that the target object in the fluid to be measured 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 object through the metal. The change in voltage value generated by the layer is used to measure the change in quantity or concentration 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 using a plurality of sensing chips with fluid devices in a sub-area detection manner, thereby improving the detection accuracy by increasing the sample volume of the fluid to be detected.

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

According to the above object, the present invention discloses a sensing chip with a fluid device, including: a substrate having a first area and a second area; a field effect transistor disposed in the first area of the substrate, and the field effect transistor includes: a first gate, a source and a drain, and the first gate is disposed on the source and the drain; and a fluid device disposed on the second region of the substrate and electrically connected to 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 area, where the area enclosed by the window is the accommodation space; the second gate is arranged in the window of the isolation layer, and the second gate depends upward from the substrate. The sequence includes a polycrystalline silicon layer and one or more metal layers; and a reference electrode, which is disposed on the second area 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 measured, multiple receptors on the metal layer are used to capture multiple targets in the fluid to be measured, and a second The voltage value of the metal layer of the gate will change as the number of these targets captured by these receptors, and the second gate transmits the voltage value change of the metal layer to the external processing unit through the field effect transistor to respond to the voltage value change. Processed to calculate target concentration.

In a preferred embodiment of the present invention, the reference electrode is in contact with the fluid to be measured when the fluid to be measured is contained in the accommodation space and supplies the voltage required for measuring changes in the voltage value of the metal layer of the second gate. .

The invention discloses another sensing chip with a fluid device, including: a substrate having a first area and a second area; a field effect transistor disposed in the first area of the substrate, the field effect transistor including a first gate, a source pole and drain, the first gate is disposed between the source and the drain and on the substrate; and a fluid device is disposed in the second area of the substrate and electrically connected to 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, where the area surrounded by the window is the accommodation space; the second gate is arranged in the window of the isolation layer, and the second gate includes a polycrystalline silicon layer and a One or more metal layers; and a reference electrode, adjacent to the second gate and disposed on the second area 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 accommodation space, so that The metal layer of the second gate contacts the fluid to be measured. One end of the polycrystalline silicon layer in the second gate is used for grounding and the other end of the polycrystalline silicon layer is electrically connected to the temperature control unit. The temperature control unit provides a temperature control signal, and The temperature control signal is used through the polycrystalline silicon layer to heat and regulate the temperature of the fluid to be measured in the accommodation space, so that when the temperature of the fluid to be measured reaches the preset temperature, multiple receptors on the surface of the metal layer are 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 multiple targets captured by the multiple receptors, and the second gate will The voltage value changes are transmitted to the external processing unit via the field effect transistor with corresponding current value changes, and are processed by the external processing unit To obtain concentration values of multiple target objects in the fluid to be measured at a preset temperature corresponding to changes in the voltage value of the metal layer.

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

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

According to the above object, the present invention also discloses another sensing chip with a fluid device, including: a substrate having a first area and a second area; a field effect transistor disposed in the first area of the substrate, the field effect transistor including A first gate, a source and a drain, and the first gate is disposed on the source and the drain; and a fluid device disposed in the second region of the substrate and electrically connected to the field effect transistor, wherein the fluid device includes: The isolation layer has a window and is disposed on the second area of the substrate to expose the surface of the substrate in the second area, where the area surrounded by the window is the accommodation space; the second gate is disposed in the window of the isolation layer , the second gate includes a polycrystalline silicon layer and one or more metal layers from the substrate upward, whereby when the sensing chip with the fluid device is placed in an environment with the fluid to be measured, and the fluid to be measured passes through the fluid device When a voltage is applied to the second gate polycrystalline silicon layer of the fluid device, multiple charges will be generated on the surface of the metal layer of the second gate and the receptor. Each charge on the metal layer is used to capture the second gate in the fluid device. Target objects 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 measured.

In a preferred embodiment of the present invention, the charges may be positive charges or negative charges.

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 a gas.

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

1. 1000: Sensing chip with fluid 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:Jiji

30:Isolation layer

302:Window

40, 4000: second gate

402, 4002: Polycrystalline silicon layer

404, 4004: One or more metal layers

406, 4006, 4006A, 4006B, 4006C, 4006D: Receiver

50:Reference electrode

60: Fluid to be measured

602, 602A, 602B, 602C, 602D: target

7: Sensing chip with fluidic device

70:Substrate

70A:First area

70B:Second area

80: Second gate

802:Polycrystalline silicon layer

804: One or more metal layers

8042:Charge

806:Receiver

90: Fluid to be measured

902:Target

Test A, Test B, Test C, Test D: block

Step S10-Step S20: Flowchart of steps when a sensing chip with a fluid device detects a liquid to be measured

1A is a schematic diagram illustrating an embodiment of a sensing chip with a fluidic device according to the technology disclosed in the present invention.

1B is a schematic circuit diagram illustrating 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 fluid device according to the technology disclosed in the present invention.

3A is a top view of another embodiment of a sensing chip having multiple fluidic devices according to the technology disclosed in the present invention.

3B is a top view showing that the sensing element is composed of a plurality of sensing chips with fluid devices and detects different targets in the same fluid to be measured in a partitioned manner according to the technology disclosed in the present invention.

4A is a schematic diagram illustrating another implementation of a sensing chip with a fluidic device 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 flowchart showing the steps of detecting a target object in a fluid to be measured by a sensing chip having a fluid device according to the technology disclosed in the present invention.

6 is a schematic diagram showing a sensing chip with a fluid device detecting fluid to be tested containing E. coli according to the technology disclosed in the present invention.

First please refer to Figure 1A. FIG. 1A shows a schematic structural diagram of a sensing chip with a fluidic device. In FIG. 1A , a sensing chip 1 with a fluid device is composed of a field effect transistor (FET) 20 and a fluid device. The sensing chip 1 with a fluid device includes a substrate 10. A dotted line is provided on the substrate 10 to divide it into a first area 10A and a second area 10B. Here, the substrate 10 is divided into a first area 10A and a second area 10B. In order to make the subsequent description easy to understand, there will be no dotted lines on the actual substrate 10 . A field effect transistor 20 is provided in the first region 10A of the substrate 10. The field effect transistor 20 is, for example, an N-type metal oxide semiconductor (NMOS). Its structure at least includes a gate 202, a source 204 and a drain 206. The gate 202 is between the source electrode 204 and the drain electrode 206 and is disposed on the substrate 10. The source electrode 204 and the drain electrode 206 are disposed in the first region 10A of the substrate 10. There is also a Isolation layer (or field oxide layer) 30 . It should be noted that the above-mentioned isolation layer 30, gate 202, source 204 and drain 206 are formed using a suitable complementary metal oxide semiconductor (CMOS) process. The formation steps are not the main technical features of the present invention and are not discussed here. Make more statements.

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

In this embodiment, the area surrounded by the window 302 of the isolation layer 30 on the second area 10B is used as a receiving space to accommodate the fluid 60 to be tested (as shown in FIG. 1B ). Therefore, when the fluid 60 to be tested is placed In this accommodating space 302, the fluid 60 to be tested is allowed to contact the metal layer 404 of the second gate 40 for a period of time, and then the voltage value of the metal layer 404 is observed to change, and the content of the fluid to be tested 60 is determined by the change in the voltage value. Whether there is a target 602 and the concentration of the target 602 will be described in detail later.

Next, please refer to Figure 1B. Figure 1B shows a circuit schematic of a sensing chip 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 60 to be measured is placed on After the accommodating space 302 of the sensing chip 1 of the fluid device is provided, the fluid 60 to be measured is allowed to contact the plurality of receptors (receptors) 406 on the metal layer 404 of the second gate 40 of the fluid device and allowed to stand for at least 30 minutes. , during the standing process, these receptors 406 are used to capture the target object (or target molecule) 602 in the fluid 60 to be measured. It should be noted that the receptors 406 are processed by the antibody after the production of the sensing chip 1 It is fixed on the metal layer 404 during the process.

For example, the fluid 60 to be tested may be a BTP buffer containing an unknown target concentration, whole blood or plasma. When the fluid 60 to be tested is whole blood or plasma, the BTP buffer may be used to The fluid to be tested 60 is diluted, and then the diluted fluid to be tested 60 is placed in the accommodation space 302 of the fluid device (as shown in FIG. 1A ), that is, where the second gate 40 is located, and the diluted fluid to be tested 60 is Let it stand for a period of time. This standing time is not only to allow the metal layer 404 of the second gate 40 to have sufficient contact time with the diluted fluid to be measured 60, but also to allow the receptor 406 on the metal layer 404 to have enough time. Capture the target object 602 in the diluted fluid to be measured 60. When the plurality of receptors 406 on the surface of the metal layer 404 of the second gate 40 capture the target object 602 in the diluted fluid to be measured 60, the metal layer The voltage value of 404 will change with the number of targets 602 captured by the receptor 406, and then the current value changed by the metal layer 404 of the second gate 40 is output through the field effect transistor 20 (i.e., 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 target 602 in the diluted 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 can be an organism. When the fluid to be tested 60 is a BTP buffer, the target object 602 in the BTP buffer can be yeast, bacteria, viruses or proteins. And when the fluid 60 to be measured is plasma, the target objects 602 in the plasma may be cells.

Next, please refer to Figure 2. FIG. 2 is a schematic diagram showing yet another implementation of a sensing chip with a fluid device disclosed in the present invention. In FIG. 2 , the structure, connection relationship and function of each element of the sensing chip 1 with a fluid device are the same as those in the aforementioned FIGS. 1A and 1B , and will not be further described here. The difference between Figure 2 and the aforementioned Figures 1A and 1B is that one end of the polycrystalline silicon layer 402 in the second gate 40 is connected to the ground (GND) (ie, the left side of Figure 2) and the other end of the polycrystalline silicon layer 402 is connected to the temperature control unit. 15 is electrically connected and the sensing chip 1 with the fluid device is electrically connected to the temperature sensing circuit 17 . In this embodiment, the temperature sensing circuit 17 is used to measure the temperature of the sensing chip 1 having a fluid device, and the temperature control unit 15 is used to provide a temperature control signal, and control the polycrystalline silicon layer 402 with the width of the temperature control signal. temperature, thereby heating the fluid to be measured 60 in the accommodation space. Since the target 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, the target object 602 in the fluid to be measured 60 will The target object 602 is more easily captured by the receptor 406 on the metal layer 404, and its detailed detection steps are as follows. In addition, the connection positions of the ground terminal of the polycrystalline silicon layer 402 and the temperature control unit 15 shown in FIG. 2 can be interchanged left and right.

First, the fluid 60 to be measured is placed in the sensing chip 1 with the fluid device. Specifically, the fluid 60 to be measured is dropped into the accommodation space. Then, the temperature control unit 15 provides temperature control signal transmission The polycrystalline silicon layer 402 is used to heat the fluid to be measured, and the temperature of the polycrystalline silicon layer 402 is controlled by the width of the temperature control signal, thereby further controlling the temperature of the fluid to be measured 60 so that the temperature of the fluid to be measured 60 can be adjusted after a period of heating time. Reach the preset temperature, where the preset temperature range is 50℃-95℃. In another embodiment, if biological detection is performed, the biological target may be destroyed due to excessive temperature. Therefore, when performing biological detection, the default temperature is 90°C, 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 heat the fluid 60 to be measured through the polysilicon layer 402. At the same time, the temperature sensing circuit 17 continuously measures the temperature of the entire sensing chip 1 with the fluid device. The temperature is used to control the temperature of the fluid to be measured 60 and the sensing chip 1 with the fluid device at a fixed temperature. Accordingly, it can be measured during the process of heating the temperature of the fluid to be measured 60 to the preset temperature. The concentration or quantity of the target object 602 in the fluid 60 to be measured. Specifically, when the temperature control unit 15 is used to heat the fluid 60 to be measured, the target 602 in the fluid 60 to be measured will produce a change in kinetic energy due to the increase in temperature. This change in kinetic energy will drive the target 602 to move in the fluid to be measured. Movement or decomposition in the measured fluid 60 is more easily captured by the plurality of receptors 406 on the surface of the metal layer 404. As described in FIG. 1A and FIG. 1B , during the heating process, the voltage value of the metal layer 404 of the second gate 40 will change with the number of target objects 602 captured by the multiple receptors 406 , and the second The gate 40 transmits the voltage value change of the metal layer 404 to the external processing unit (not shown in the figure) via the field effect transistor with the corresponding current value change, and is processed by the external processing unit (not shown in the figure) until After the temperature of the fluid to be measured 60 reaches the preset temperature and the current value no longer changes, at this time, multiple voltage values in the fluid to be measured 60 corresponding to changes in the voltage value of the metal layer 404 at the preset temperature can be obtained. The concentration value of target 602.

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

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. However, in order to avoid the excessive number of target objects 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 accuracy, the present invention also discloses another sensing chip 1000 with a fluid device, as shown in FIG. 3A . Figure 3A is a top view of another embodiment of a sensing chip with a fluidic device. In FIG. 3A , the sensing chip 1000 with a fluid device 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 of the sensing chip 1000 in this embodiment is The device also has an isolation layer (not shown in the figure), a second gate 4000 and a reference electrode (not shown in the figure). The second gate 4000 is also disposed in an isolation layer having a window (not shown in the figure). The second gate 4000 on the substrate (not shown in the figure) is a polysilicon layer 4002 and one or more metal layers 4004 in sequence. In this embodiment, the polycrystalline silicon layer 4002 in the second gate 4000 is a continuous whole layer, and the metal layer 4004 is arranged on the polycrystalline silicon layer 4002 in a subdivided manner. Each metal layer 4004 is connected to a field effect electrode. The crystal 20 is electrically connected, and the field effect transistor 20 connects these output currents in parallel to calculate the change in the total output current.

In another embodiment, the sensing element is composed of a plurality of sensing chips 1000 having a fluid device. Similarly, each sensing chip 1000 having a fluid device is composed of a fluid device and a field effect transistor 20. The fluidic device is composed of an isolation layer (not shown in the figure), a reference electrode (not shown in the figure) and a second gate 4000. The second gate 4000 is composed of a polycrystalline silicon layer 4002 and one or more metal layers. 4004, that is, a polycrystalline silicon layer 4002 corresponds to one or more metal layers 4004. The second gate 4000 of the fluid device is used to capture the target 602 of the fluid 60 to be measured and further detect it. By using the sensing chip 1000 with the fluid device having two different structural designs, the target 602 can be A larger quantity of fluid 60 to be measured is detected by the second gate 4000 of the sensing chip 1000 having a fluid device in a sub-area manner. Similarly, the second gate 4000 in each sensing chip 1000 having a fluid device is electrically connected to a field effect transistor 20, so that when the second gate 4000 in each sensing chip 1000 having a fluid device After contacting the fluid 60 to be measured, the voltage value changes 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 using this area-by-area detection method to determine whether there is a target object 602 in the fluid to be measured 60 in each partition area, the concentration of the target object 602 in the fluid to be measured 60 in a partition area can also be obtained, and The sum of these concentration targets 602 per unit area is the sum of the targets 602 of the entire fluid 60 to be measured. Accordingly, by using sensing elements with multiple sensing chips 1000 having fluid devices, detection is performed in different areas. And the output parallel connection method improves the sensitivity of detection, simultaneously increases the sample volume of the corresponding fluid 60 to be measured, and increases the accuracy of the detection results.

Next, please refer to FIG. 3B . FIG. 3B shows that the sensing element is composed of a plurality of sensing chips with fluid devices and detects different targets in the same fluid to be measured in a partitioned manner. In Figure 3B, the structure of the sensing element is the same as that in Figure 3A. Here, the multiple sensing chips on the sensing element are divided into four blocks: Test A, Test B, Test C and Test D. In these four blocks In each block, the receptors on the second gate 4000 of the fluid device of the sensing chip on the same block are the same, but the receptors in different blocks are different. Therefore, in the Test A block and the Test B block , the receivers in the Test C block and Test D block are 4006A, 4006B, 4006C and 4006D respectively. In this embodiment, the purpose of dividing into different blocks is to capture different types of target objects 602A, 602B, 602C and 602D in the same fluid 60 to be measured. Therefore, similarly, the fluid 60 to be measured is accommodated in the accommodating space 302 of the sensing chip 1 with the fluid device as shown in FIGS. 1A and 1B above. Due to the different blocks Test A, Test B, Test C and Acceptance in Test D The devices 4006A, 4006B, 4006C and 4006D are different, so the target objects 602A, 602B, 602C and 602D to be captured in the fluid 60 to be measured are also different. Therefore, with this sensing element, the metal layer of the second gate 4000 in the Test A block, Test B block, Test C block and Test D block can be set according to the target object 602 that the user wants to detect. The types of receivers 4006A, 4006B, 4006C and 4006D on 4004, accordingly, different target objects 602A, 602B, 602C and/or can be captured in the same fluid 60 to be tested at the same detection time. Or target object 602D, which can greatly save the user's operating time and manpower.

Next, please refer to Figure 4A. FIG. 4A is a schematic diagram illustrating another implementation of a sensing chip with a fluidic device disclosed in the present invention. In Figure 4A, the sensing chip 7 with a fluid device is also composed of a field effect transistor 20 and a fluid device 80. The sensing chip 7 with a fluid device includes a substrate 70, and a dotted line is provided on the substrate 70 to distinguish It is divided into a first region 70A and a second region 70B. The first region 70A of the substrate 70 is provided with a field effect transistor 20, such as an N-type metal oxide semiconductor (NMOS). Its structure and formation method are the same as those in FIG. 1A. Add more statements. An isolation layer 30 is provided on the second region 70B of the substrate 70 . The isolation layer 30 has a window 302 , and the window 302 is used to expose the surface of the substrate 10 in the second region 10B.

The fluid device is disposed on the second region 70B of the substrate 70 and is electrically connected to the field effect transistor 20 . The fluid device includes: an isolation layer 30 and a second gate 80 . The isolation layer 30 has a window 302. The window 302 is used to expose the surface of the substrate 70 in the second area 70B, and the area surrounded by the window 302 is an accommodation space. The second gate 80 is disposed in the window 302 of the isolation layer 30 . The second gate 80 includes a polysilicon layer 802 and one or more metal layers 804 in sequence from the substrate 70 upward.

In this embodiment, the area surrounded by the window 302 of the isolation layer 30 is used as an accommodation space. This accommodation space is used to accommodate the fluid 90 to be measured (as shown in FIG. 2B ). Therefore, when the fluid 90 to be measured is contained in place here After accommodating the space 302, the fluid to be measured 90 will contact the metal layer 804 of the second gate 80, causing the voltage value of the metal layer 804 to change. The detailed operation will be described later. The fluid 90 to be measured in this embodiment is gas.

Next, please refer to Figure 4B. Figure 4B shows a circuit schematic of a sensing chip with a fluidic device. In FIG. 4B , the source electrode 204 of the field effect transistor 20 is connected to ground, and the drain electrode 206 is connected to an external processing unit (not shown in the figure). During operation, the sensing chip 7 with the fluid device is placed in an environment with the fluid to be measured 90, and after leaving it 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 better voltage value range can 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 with electrical properties opposite to 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, suspended particles or gas molecules in the fluid to be measured 90; similarly, if the polycrystalline silicon layer 802 applied to the second gate 80 is If a negative voltage is applied to the surface of the metal layer 804 of the second gate 80, a plurality of positive charges (not shown in the figure) opposite to the polarity of the polycrystalline silicon layer 802 will be generated, and bacteria with negative charges in the fluid 90 to be measured will , viruses, suspended particles or gas molecules will affect the charge of these positively charged particles.

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 the fluid to be measured will Targets 902 with positive charges within 90 such as bacteria, viruses, suspended particles or gas molecules will affect the amount of negative charge 8042, and the voltage value of the metal layer 804 of the second gate 80 will change with the surface of the metal layer 804. These targets 902 are changed, and then the current value generated by the metal layer 804 of the second gate 80 is transmitted to an external processing unit (not shown in the figure) through the field effect transistor 20, and the corresponding value of the metal layer 804 can be obtained. The voltage value corresponds to the concentration value (or quantity) of the target object 902 in the fluid 90 to be measured.

In another embodiment, in order to obtain the concentration of various target objects 902 in the fluid 90 to be measured under unit volume, the target objects 902 can be bacteria, viruses, suspended particles or gas molecules, corresponding to each different The target 902 is used to change the receptor 806 in the second gate 80 of the sensing chip 7 with a fluid device. As mentioned above, the sensing elements of the sensing chip 7 with a fluid device (not shown in the figure) will be arranged in an array. (represented) is placed in a 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 fluid device, and the second gate electrode 80 of each sensing chip 7 with a fluid device in the array is The surface of the metal layer 804 of the gate 80 will generate negative charges (or positive charges), and capture various targets 902 corresponding to the fluid 90 to be measured according to the type of each receptor 806. Each of the arrays has a fluid device. The voltage values generated after the target is captured by the sensing chip 7 are respectively converted by the field effect transistor 20 of each sensing chip 7 with a fluid device to generate a corresponding current value, and then each current value is passed through The field effect transistor 20 is output to an external processing unit (not shown in the figure), and the concentrations of different types of target objects 902 in the fluid to be measured 90 can be obtained based on each current value.

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

Next, step S14: soak the sensing chip with the fluid device in a buffer solution to measure the base line. In this step, the sensing chip 1 with the fluid device is first immersed in the buffer solution. Since there is no target in the buffer solution, there is fluid The surface of the metal layer 404 of the second gate 40 of the sensing chip 1 of the device and the receiver 406 will not affect the voltage, but the voltage value of the sensing chip 1 with the fluid device can be supplied by the reference electrode 50 after being soaked in the buffer solution. And the voltage value transmitted to the external processing device (not shown in the figure) through the field effect transistor 20. This voltage value is the voltage value provided by the reference electrode to the metal layer 404 itself, thereby obtaining the drain current and gate voltage. A base line, which can be used for comparison with the subsequent detection of the fluid to be tested with target objects.

In step S16: place the fluid to be measured on the sensing chip with the fluid device, and let it stand for 30 minutes before cleaning and testing. In this step, the fluid 60 to be measured is accommodated in the sensing chip 1 with the fluid device, and left for 30 minutes, so that the fluid 60 to be measured can interact with the second gate 40 of the sensing chip 1 with the fluid device. Metal layer 404 is fully in contact. During the standing process, the receptors 406 on the surface of the metal layer 404 are used to capture the target 602 in the fluid 60 to be measured. As mentioned above, after the receptor 406 captures the target object 602, it will cause the voltage value of the metal layer 404 to change in the subsequent step 20.

Next, step S18: Clean the sensing wafer with the fluid device using a buffer solution. In this step, the sensing chip 1 with the fluid device that was soaked in the buffer solution in step S16 is cleaned with a new buffer solution. For the accuracy of detection, the cleaning step is required for the sensing chip 1 with the fluid device.

Step S20: Repeat step S14 to compare the detection result with the original baseline to determine whether there is a target object in the fluid to be measured and the concentration of the target object. In this step, the detection result obtained in the aforementioned step S14 is compared with the baseline. In addition to judging whether there is a target 602 in the fluid 60 to be measured by the change of the voltage value, it can also be determined by the voltage value. The voltage value is used to estimate the concentration of the target 602 in the fluid 60 to be measured.

Based on the above steps, FIG. 6 is a schematic diagram showing the comparison between the baseline and the fluid to be tested containing three different concentrations of E. coli. In Figure 6, the baseline is obtained using a buffer solution. Then according to the above-mentioned steps S18 to step S20, the fluids to be tested with different concentrations of E. coli are placed in the sensing chip 1 with the fluid device for detection, where the concentrations of E. coli are 10 ² cells/ml, 10 ⁴ /cells/ml and 10 ⁶ cells/ml. From Figure 6, in addition to the fact that the sensing chip 1 with a fluid device can detect E. coli in the fluid to be measured, it can also be seen that under the same voltage conditions, the higher the concentration of different E. coli, the higher the sensor chip 1 with the fluid device. The changes in the current value of the metal layer 404 of the second gate 40 of the measured chip 1 are also different.

To sum up the above, the sensing chip 1, 7, 1000 with the fluid device disclosed in the present invention can not only detect the fluid to be measured in the form of liquid or gas, but also can detect the target 602 and target 602A of the fluid 60 to be measured. , the concentration of the target 602B, the target 602C, and/or the target 602D is not just to detect the presence of the target 602, the target 602A, the target 602B, the target 602C, and/or the target 602D, but The concentration of the target 602, the target 602A, the target 602B, the target 602C, and/or the target 602D in the fluid to be measured can be obtained in a short period of time, and the obtained results can be provided to subsequent relevant personnel. Research or judgment is carried out to solve the technical problem that the existing sensing chip can only detect the presence or absence of a target but cannot quantify the target.

In addition, in embodiments of the present invention, the second gates 40, 80, 4000 in the sensing chips 1, 7, 1000 with fluid devices are compatible with the current standard CMOS (complementary metal oxide semiconductor) semiconductor process. Therefore, the chip factory does not need any additional special or customized processes to complete the process, which solves the technical problem in the existing technology that the sensing chip requires a special process to complete.

1: Sensing chip with fluidic device

10:Substrate

10A: The first area

10B:Second area

20: Field effect transistor

202: Gate

204:Source

206:Jiji

30:Isolation layer

302:Window

40: Second gate

402:Polycrystalline silicon layer

404: One or more metal layers

406:Receiver

50:Reference electrode

60: Fluid to be measured

602:Target

Claims (8)

A sensing chip with a fluid device includes: a substrate having a first area and a second area; a field effect transistor disposed in the first area of the substrate, the field effect transistor including a A first gate, a source and a drain, the first gate is disposed between the source and the drain and on the substrate; and a fluid device is disposed in the second area 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 in the second area, wherein an area surrounded by the window is an accommodation space; a second gate disposed in the window of the isolation layer, the second gate including a polysilicon layer and one or more metal layers from the substrate upward; and a reference electrode adjacent to the second gate The reference electrode is disposed on the second area of the substrate, and the reference electrode is in contact with the fluid to be measured, wherein a fluid to be measured is accommodated in the accommodation space, so that the metal layer of the second gate electrode contacts To the fluid to be measured, one end of the polycrystalline silicon layer in the second gate is used to ground and the other end of the polycrystalline silicon layer is electrically connected to a temperature control unit. The temperature control unit provides a temperature control signal, and through The polycrystalline silicon layer uses the temperature control signal to heat the fluid to be measured in the accommodation space and regulate a temperature of the fluid to be measured, so that the temperature of the fluid to be measured reaches a preset temperature. A plurality of receptors on a surface of the metal layer are used to capture a plurality of targets in the fluid to be measured, and a voltage value of the metal layer of the second gate will increase as the receptors capture the The number of these targets changes, and the second gate changes the voltage value of the metal layer through A corresponding current value change is transmitted from the field effect transistor to an external processing unit, and the external processing unit processes it to obtain the changes in the target objects in the fluid to be measured corresponding to the voltage value change of the metal layer. A concentration value at the preset temperature. The sensing chip with a fluid device as claimed in claim 1, wherein the reference electrode is in contact with the fluid to be measured and is used to provide a signal required for measuring changes in the voltage value of the metal layer of the second gate. voltage. The sensing chip with a fluid device as claimed in claim 1, wherein the temperature control unit is a pulse width modulation unit (PWM). The sensing chip with a fluid device as described in claim 1, wherein the preset temperature range is 50°C-95°C. A sensing chip with a fluid device includes: a substrate having a first area and a second area; a field effect transistor disposed in the first area of the substrate, the field effect transistor including a A first gate, a source and a drain, the first gate is disposed between the source and the drain and on the substrate; a fluid device is disposed in the second area of the substrate and connected with The field effect transistor is electrically connected, and the fluid device includes: an isolation layer having a window, and is disposed on the second area of the substrate to expose a surface of the substrate in the second area, wherein the window An area enclosed is an accommodation space; and a second gate is disposed in the window of the isolation layer. The second gate includes a polycrystalline silicon layer and one or more metal layers from the substrate upward. , Thereby, when the sensing chip with the fluid 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 fluid device, the third gate of the fluid device is When a voltage is applied to the second gate, a plurality of charges will be generated on a surface of the metal layer of the second gate, and a charged amount of each charge on the metal layer will be transferred to a target object in the fluid to be measured. influence, and a voltage value of the metal layer of the second gate will change with the number of the targets captured by the charges, and the second gate will pass the voltage value of the metal layer through the field effect The transistor is sent to an external processing unit to process the voltage and current values. The sensing chip with a fluidic device as claimed in claim 5, wherein the voltage is less than 30 volts. The sensing chip with a fluid device as described in claim 5, wherein the fluid to be measured is a gas. The sensing chip with a fluid device as claimed in claim 5, wherein the target may be bacteria, viruses, suspended particles or gas molecules.