TWI660173B - Biosensing system - Google Patents

Abstract

A biological sensing system includes a field effect transistor, a sensing chip, and an external capacitor. The field effect transistor contains a gate. The sensing chip is electrically connected to the gate electrode through a wire. The external capacitor includes a first terminal and a second terminal, the first terminal is electrically connected to the lead, and the second terminal is electrically connected to the ground electrode.

Description

Biosensing system

This disclosure relates to a biosensor system.

In recent years, biosensors made by combining nanowire field effect transistors produced by electrochemical, microelectronics, and nanotechnology have extremely high sensitivity and selectivity, and have the characteristics of immediate measurement without label modification In the recent application of biomedical testing, it has attracted considerable attention and expectation. Common nanotube biosensors include Silicon Nanowire (SiNW) and Carbon Nanotube (CNT) developed using one-dimensional semiconductor nanomaterials.

Taking silicon nanowire field-effect transistor (SiNW-FET) as an example, a general design includes a three-electrode system: a source (S), a drain (Drain), and a gate (Gate). The source and drain are bridged by a semiconductor channel, and the gate is responsible for regulating the conductance of the channel. Then, a specific receptor is used as a sensing element on the surface modification of the silicon nanowire. This receptor can be an antibody. When the system is exposed to a solution environment containing specimens, such as proteins, DNA, RNA, etc., the specimens and receptors will bind to the surface of the SiNW-FET. At this time, the electric field formed by the charge carried by the biomolecule will affect the SiNW-FET The number of electrons or holes, which will cause the conductivity to rise or fall.

The present disclosure relates to a biosensor system, including a field effect transistor, a sensing chip, and an external capacitor. The field effect transistor contains a gate. The sensing chip is electrically connected to the gate electrode through a wire. The external capacitor includes a first terminal and a second terminal, the first terminal is electrically connected to the lead, and the second terminal is electrically connected to the ground electrode.

In some embodiments, the biosensor system further includes a liquid cell to polarize the reference electrode. The liquid tank contains a solution and the wafer is contacted with the solution. The reference electrode is in contact with the solution.

In summary, the bio-sensing system proposed in this disclosure can be used to sense the concentration of the specimen in the liquid tank. Before the sensing function is performed, the reference electrode applies a DC bias voltage to the biosensor system, and the capacitance makes the overall electrical property of the biosensor system quickly reach a stable state.

100‧‧‧Biosensor System

110‧‧‧Field Effect Transistor

111‧‧‧ Drain

112‧‧‧Source

113‧‧‧Gate

114‧‧‧Nano wire

115‧‧‧ Insulation

116‧‧‧ substrate

117‧‧‧ thermal oxide layer

120‧‧‧Sensor Chip

121‧‧‧ substrate

122‧‧‧oxide

123‧‧‧ conductive layer

124‧‧‧First material layer

125‧‧‧Second material layer

126‧‧‧third material layer

127‧‧‧ receptor

130‧‧‧Wire

141‧‧‧ the first end

142‧‧‧second end

150‧‧‧ liquid tank

151‧‧‧solution

152‧‧‧ specimen

160‧‧‧Reference electrode

C‧‧‧ Sensing Chip Double Electric Layer Capacitance

C ₁ ‧‧‧ the first equivalent capacitance

C ₂ ‧‧‧Second Equivalent Capacitance

C _ex ‧‧‧external capacitor

C _O ‧‧‧ electrode capacitance of sensor chip

C _p ‧‧‧parasitic capacitance

C _T ‧‧‧Gate capacitor of field effect transistor

L1, L2‧‧‧lines

R‧‧‧ Double-layer resistance of the sensor chip

R ₁ ‧‧‧first equivalent resistance

R ₂ ‧‧‧Second equivalent resistance

R _O ‧‧‧ electrode resistance of sensor chip

R _T ‧‧‧Gate resistance of field effect transistor

R _solution ‧‧‧ solution resistance

S1‧‧‧first voltage source

S2‧‧‧Second voltage source

S3‧‧‧Third voltage source

V _T ‧‧‧Gate voltage level

V _e ‧‧‧ surface voltage level of sensor chip

V _int ‧‧‧ initial voltage level

V _sta ‧‧‧ stable voltage level

FIG. 1A is a schematic three-dimensional view of a biosensor system according to an embodiment of the disclosure.

FIG. 1B is a cross-sectional view of a field effect transistor according to an embodiment of the disclosure.

FIG. 1C is a cross-sectional view of a sensing chip according to an embodiment of the disclosure.

Figure 2 shows the voltage level-time relationship measured at the gate when the biosensor system in Figure 1A is not provided with a capacitor.

FIG. 3 is a voltage level-time relationship diagram measured at the gate electrode when the capacitance of the biosensor system in FIG. 1A has an ideal capacitance value.

FIG. 4 is a schematic diagram of an equivalent circuit of each component in the biosensor system in FIG. 1A.

FIG. 5 shows an equivalent circuit diagram further simplified from FIG. 4.

Figure 6 shows the voltage level-time relationship measured by the biosensor system.

In the following, a plurality of embodiments of the present invention will be disclosed graphically. For the sake of clarity, many practical details will be described in the following description. It should be understood, however, that these practical details should not be used to limit the invention. That is, in some embodiments of the present invention, these practical details are unnecessary. In addition, in order to simplify the drawings, some conventional structures and components will be shown in the drawings in a simple and schematic manner. And, unless otherwise indicated, the same component symbols in different drawings may be regarded as corresponding components. These drawings are shown for the purpose of clearly expressing the connection relationship between the elements in these embodiments, and are not intended to show the actual dimensions of the elements.

Please refer to FIG. 1A, which illustrates a three-dimensional schematic diagram of the biosensor system 100 according to an embodiment of the disclosure. As shown in FIG. 1A, the biosensor system 100 includes a field effect transistor (FET) 110, a sensing chip 120, a wire 130, an external capacitor C _ex , a liquid tank 150, and a reference electrode 160. The field effect transistor 110 includes a drain electrode 111, a source electrode 112, and a gate electrode 113. The gate electrode 113 is electrically connected to the sensing chip 120 through a wire 130. The external capacitor C _ex includes a first terminal 141 and a second terminal 142. The first terminal 141 is electrically connected to the wire 130, and the second terminal 142 is electrically connected to the first voltage source S1. In this embodiment, the first voltage source S1 provides a ground quasi-voltage V _g . A solution 151 is loaded in the liquid tank 150, and the sensing wafer 120 contacts the solution 151. The reference electrode 160 is in contact with the solution 151 and is electrically connected to the second voltage source S2. Through the above configuration, the biosensor system 100 can sense the concentration of a specific component in the solution 151 by the voltage level measured by the gate 113. The detailed principle and device details will be explained later.

As shown in FIG. 1A, the field effect transistor 110 in this embodiment is a junctionless nanowire field effect transistor (JN FET). The drain 111 and the source 112 in the field effect transistor 110 are connected by a nano wire 114, and the nano wire 114 can be used as a channel between the drain 111 and the source 112. The gate 113 covers the nanowire 114, and an insulating layer 115 is provided between the gate 113 and the nanowire 114 to separate the two.

In this embodiment, the material of the nano-wire 114 includes silicon (Si), the material of the insulating layer 115 includes silicon oxide (SiO ₂ ) and silicon nitride (Si ₃ N ₄ ), and the material of the gate 113 includes polycrystalline silicon. In this embodiment, the silicon material of the nanowire 114 is N-type doped, and the polycrystalline silicon material of the gate 113 is P-type doped. In the state where no voltage is applied to the gate 113, the work function difference between the gate 113 and the nanowire 114 will cause a depletion region within the nanowire 114, and the charge carriers cannot be drawn. The electrode 111 and the source electrode 112 circulate. When a voltage is applied to the gate electrode 113, the empty area in the nanowire 114 is reduced (or disappeared), so that the charge carriers can flow between the drain 111 and the source 112. In summary, the voltage level of the gate electrode 113 will affect the electrical property between the drain electrode 111 and the source electrode 112.

It should be understood that the field effect transistor 110 shown in FIG. 1A is for illustrative purposes only. The actual stacked structure of the field effect transistor 110 can be referred to FIG. 1B, which illustrates a cross-sectional view of the field effect transistor 110 according to an embodiment of the present disclosure. As shown in FIG. 1B, the field effect transistor 110 further includes a substrate 116. A thermal oxidation layer 117 is provided on the substrate 116. The thermal oxidation layer 117 is provided with a drain electrode 111, a source electrode 112, and a nanowire 114. A portion of the thermal oxidation layer 117 between the drain electrode 111 and the source electrode 112 is recessed toward the substrate 116, and the insulating layer 115 and the gate electrode 113 cover the nanowire 114 at the recess of the thermal oxidation layer 117.

Now go back to Figure 1A. The gate 113 of the field effect transistor 110 is electrically connected to the sensing chip 120 through a wire 130, so that the sensing chip 120 and the gate 113 are electrically coupled. That is, the voltage levels of both the sensing chip 120 and the gate electrode 113 are the same. When the voltage level of the sensing chip 120 is changed, the voltage level of the gate electrode 113 is also changed together. In this embodiment, the sensing chip 120 can be used as a capacitive sensing electrode.

It should be understood that the sensing chip 120 shown in FIG. 1A is for illustrative purposes only. The actual stacked structure of the sensing chip 120 can be referred to FIG. 1C, which illustrates a cross-sectional view of the sensing chip 120 according to an embodiment of the present disclosure. As shown in FIG. 1C, the sensing wafer 120 includes a substrate 121, an oxide layer 122, a conductive layer 123, a first material layer 124, a second material layer 125, and a third material layer 126.

In this embodiment, the conductive layer 123 and the conductive wire 130 of the sensing chip 120 can serve as extensions of the gate electrode 113. That is, the materials of the conductive layer 123 and the wire 130 may be the same as those of the gate electrode 113, and both of them include polycrystalline silicon. For example, the conductive layer 123 may be polycrystalline silicon with a thickness of about 380 nanometers. In this embodiment, the substrate 121 may be a silicon substrate, the oxide layer 122 may be silicon oxide (SiO ₂ ) having a thickness of about 2.5 μm, the first material layer 124 may be aluminum (Al) having a thickness of about 100 nm, and the second The material layer 125 may be aluminum oxide (Al ₂ O ₃ ) with a thickness of about 10 nm, and the third material layer 126 may be silicon nitride (Si ₃ N ₄ ) with a thickness of about 8 to 10 nm.

In some embodiments, the sensing chip 120 is detachably connected to the gate 113 of the field effect transistor 110. That is, the sensing chip 120 can be discarded. For example, the wire 130 may be disconnected to separate the sensing chip 120 from the field effect transistor 110. Then, the new sensing chip 120 can be electrically connected to the wire 130. In this way, the field effect transistor 110 can be repeatedly used, which effectively saves costs.

Now go back to Figure 1A. In this embodiment, the sensing wafer 120 is disposed below the liquid tank 150, and one surface of the sensing wafer 120 contacts the solution 151 in the liquid tank 150. In this embodiment, the solution 151 is a phosphate buffered saline (PBS). On the other hand, the reference electrode 160 is immersed in the solution 151 and is connected to the second voltage source S2. The second voltage source S2 can provide a fixed DC bias voltage V _ref .

When the second voltage source S2 is turned off, the entire biosensor system 100 is in an initial state. After turning on the second voltage source S2 and providing the reference electrode 160 with a fixed DC bias voltage V _ref , the charge and voltage distribution in the entire biosensor system 100 will change accordingly. The change of the charge and voltage distribution in the biosensor system 100 over time is affected by the external capacitance C _ex .

Please refer to Figure 1A and Figure 2 together. FIG. 2 shows the voltage level measured at the gate 113 when the capacitance value of the external capacitance C _ex of the biosensor system 100 in FIG. 1A is equal to zero (it can be considered that the external capacitance C _{ex is} not set)- Time diagram. As shown in FIG. 2, when the second voltage source S2 is turned on, the voltage level V _{T of the} gate 113 will quickly rise to an initial voltage level V _int . After a period of time, the charge and voltage distribution inside the entire biosensor system 100 reaches a stable state. At this time, the voltage level V _{T of the} gate 113 changes to a stable voltage level V _sta . In this embodiment, the voltage level V _T of the gate 113 is reduced to a stable voltage level V _sta , but it is not limited thereto.

It can be inferred from FIG. 2 that the larger the difference between the initial voltage level V _int and the stable voltage level V _sta is, the time for the voltage level V _{T of the} gate 113 to fall from the initial voltage level V _int to the stable voltage level V _sta . The longer. Therefore, if the gap between the initial voltage level V _int and the stable voltage level V _sta can be reduced, the biosensor system 100 can be accelerated to a stable state.

Specifically, the value of the initial voltage level V _int can be changed by adjusting the capacitance value of the external capacitor C _ex . The capacitance of the ideal external capacitor C _ex should be such that the initial voltage level V _int is equal to the stable voltage level V _sta . Please refer to FIG. 3, which shows a voltage level-time relationship diagram measured at the gate 113 when the external capacitance C _ex of the biosensor system 100 in FIG. 1A has an ideal capacitance value. As shown in FIG. 3, in this embodiment, the initial voltage level V _int is equal to the stable voltage level V _sta . That is, after the reference electrode 160 provides a DC bias voltage V _ref , the entire biosensor system 100 quickly reaches a stable state.

There are several ways to find the ideal external capacitor C _ex . For example, the external capacitance C _ex with different capacitance values can be directly replaced in the biosensor system 100, and the gap between the initial voltage level V _int and the stable voltage level V _sta can be measured in order to select the ideal external Capacitance C _ex .

Alternatively, the ideal capacitor value can be estimated by calculation to select the ideal external capacitor C _ex . Specific calculation method can refer to Figure 4. FIG. 4 is a schematic diagram of the equivalent circuits of the components in the biosensor system 100 in FIG. 1A.

Each component in FIG. 4 may correspond to FIG. 1A to FIG. 1C, and is not repeatedly marked for the sake of brevity. As shown in FIG. 4, the field effect transistor 110 and the sensing chip 120 are electrically connected by a wire 130. On the other hand, the drain 111 of the field effect transistor 110 is further electrically connected to the third voltage source S3. In this embodiment, the third voltage source S3 provides a ground quasi-voltage V _g . However, in other embodiments, the third voltage source S3 may provide a positive bias voltage or a negative bias voltage, and the disclosure is not limited to the above.

The equivalent circuit between the second voltage source S2 to the third voltage source S3 has been shown in FIG. 4. The corresponding meanings of the symbols in the figure are arranged as follows:

As shown in FIG. 4, the voltage level V _{T is} actually the voltage level difference (that is, V _G ) between the gate 113 of the field effect transistor 110 and the ground electrode. On the other hand, _CP is a parasitic capacitance (non-solid element) in the biosensor system 100, and its value is much smaller than the capacitance value of the external capacitance _Cex . Specifically, the difference between the two values can exceed 500 times.

Please refer to FIG. 5 for an equivalent circuit diagram further simplified from FIG. 4. As shown in FIG. 5, the circuit between the lead 130 and the second voltage source S2 can be simplified into a first equivalent resistance R ₁ and a first equivalent capacitance C ₁ , and the first equivalent resistance R ₁ and The first equivalent capacitance C _{1 is} connected in parallel. The circuit between the lead 130 and the third voltage source S3 can be simplified into a second equivalent resistance R ₂ and a second equivalent capacitance C ₂ , and the second equivalent resistance R ₂ and the second equivalent capacitance C _{2 is} connected in parallel.

After the circuit of FIG. 5 is calculated, it can be learned that the initial voltage level V _int and the stable voltage level V _sta satisfy the following relationship:

That is, the proportion of each capacitance value in the biosensor system 100 will affect the initial voltage level V _int , and the proportion of each resistance value in the biosensor system 100 will affect the stable voltage level V _sta . As can be seen from the above formulas (1) and (2), in this embodiment, the size of the initial voltage level V _int can be adjusted by the external capacitor C _ex .

As mentioned above, the capacitance value of the external capacitor C _{ex should} ideally make the initial voltage level V _int equal to the stable voltage level V _sta , so the value should satisfy the following formula (3): After the capacitance value of the external capacitor C _ex is properly selected, a voltage level-time relationship diagram similar to that shown in FIG. 3 can be obtained. However, in some embodiments, the initial voltage level V _int does not need to be completely equal to the stable voltage level V _sta . For example, the initial voltage level V _int may be slightly less than or greater than the stable voltage level V _sta .

That is, in practice, it is not necessary to completely satisfy equation (3). Because in the actual situation, the specifications of commonly used capacitors must also be considered. On the other hand, as mentioned above, the sensing chip 120 is disposable. When the new sensing chip 120 is replaced, the first equivalent resistance R ₁ and the first equivalent capacitance in the biosensor system 100 are replaced. C ₁ will change slightly, and then change the initial voltage level V _int and the stable voltage level V _sta slightly. In a word, in practice, the capacitance value of the external capacitor C _ex only needs to keep the difference between the initial voltage level V _int and the stable voltage level V _sta within a certain range. For example, the error between the two can satisfy the following formula (4):

Next, please refer to FIG. 6, which illustrates a voltage level-time relationship diagram measured by the biosensor system 100. In FIG. 6, the line segment L1 represents the voltage level-time relationship diagram of the biosensor system 100 without the external capacitor C _ex after the second voltage source S2 turns on the DC bias voltage V _ref , and the line segment L2 represents the use of an external capacitor. A voltage level-time relationship diagram of the biosensor system 100 of C _ex after the second voltage source S2 turns on the DC bias voltage V _ref .

As shown by the line segment L1 in FIG. 6, the average voltage level V _T of the gate electrode 113 decreases by about 3.72 mV every ten minutes. On the other hand, the line segment L2 in FIG. 6 decreases the voltage level V _T of the gate electrode 113 by approximately 0.66 mV every ten minutes. The difference between the two is about five times. In other words, in the biosensor system 100 using the external capacitor C _ex , the voltage level V _{T of the} gate 113 changes very little (it can be regarded as being in a stable state), which is obviously better than that of the biosensor without the external capacitor C _ex .测 系统 100。 Test system 100.

It can be known from the above description of FIGS. 1A to 6 that after the second voltage source S2 turns on the DC bias voltage V _ref , the voltage level V _T of the gate 113 in the biosensor system 100 is significantly changed from the initial voltage level V _int The stable voltage level V _{sta is} quickly reached. Next, please return to FIG. 1A. After the biosensor system 100 reaches a stable state, an analyte 152 can be added to the solution 151. As shown in FIG. 1A, the surface of the sensing wafer 120 is processed in advance, and a receptor 127 is attached thereto. The specimen 152 in the solution 151 may react with the receptor 127 on the surface of the sensing wafer 120. Specifically, the specimen 152 may be attached to the receptor 127. Therefore, the concentration of the specimens 152 in the solution 151 affects the number of the specimens 152 attached to the sensing wafer 120.

The specimen 152 attached to the sensing wafer 120 changes the electrical properties of the sensing wafer 120. Since the gate electrode 113 is electrically coupled to the sensing chip 120, an external semiconductor sensing device can sense an electrical change (such as a V _T change) of the gate electrode 113 and use this electrical change to calculate the solution 151 The concentration of the intermediate sample 152. In this way, the detection function of the biosensor system 100 is achieved.

In summary, the present disclosure proposes a bio-sensing system that can be used to sense the concentration of a specimen in a liquid tank. Before performing the sensing function, The pole will apply a DC bias voltage to the biosensor system, and the capacitor will make the overall electrical property of the biosensor system reach a stable state quickly.

This disclosure has been described by examples and the above-mentioned embodiments, and it should be understood that the present invention is not limited to the disclosed embodiments. On the contrary, the present invention encompasses various modifications and approximate arrangements (eg, as would be apparent to one of ordinary skill in the art). Therefore, additional claims should be based on the broadest interpretation to cover all such changes and approximate arrangements.

Claims (8)

A biological sensing system includes: a field effect transistor including a gate; a sensing chip electrically connected to the gate through a wire; and an external capacitor (C _ex ) including a first terminal and a first terminal. Two ends, the first end is electrically connected to the wire, and the second end is electrically connected to a ground quasi electrode; a liquid tank containing a solution, wherein the sensing chip contacts the solution; and a reference electrode is contacted with the solution A first equivalent resistance R ₁ and a first equivalent capacitance C ₁ between the lead and the reference electrode, and a second equivalent resistance R ₂ and a first equivalent resistance between the lead and the ground electrode. Two equivalent capacitors C ₂ , whose values satisfy: A biological sensing system includes: a field effect transistor including a gate; a sensing chip electrically connected to the gate through a wire; and an external capacitor (C _ex ) including a first terminal and a first terminal. Two ends, the first end is electrically connected to the wire, and the second end is electrically connected to a ground quasi electrode; a liquid tank containing a solution, wherein the sensing chip contacts the solution; and a reference electrode is contacted with the solution A first equivalent resistance R ₁ and a first equivalent capacitance C ₁ between the lead and the reference electrode, and a second equivalent resistance R ₂ and a first equivalent resistance between the lead and the ground electrode. Two equivalent capacitors C ₂ , whose values satisfy: / <20%. The biosensor system according to claim 1 or 2, wherein a parasitic capacitance C _p exists between the lead and the ground quasi electrode, and a numerical relationship between the external capacitance C _ex and the parasitic capacitance C _p is as follows: C _p <C _ex . The biosensor system according to claim 3, wherein: C _p * 500 <C _ex . The biosensor system according to claim 1 or 2, wherein the sensing chip is detachably connected to the gate. The biosensing system according to claim 1 or 2, wherein the field effect transistor further comprises: a substrate; a semiconductor layer provided on the substrate; an insulating layer provided on the semiconductor layer; and a conductive Layer, disposed on the insulating layer. The biosensor system according to claim 1 or 2, wherein the sensing chip includes a capacitive sensing electrode. The biosensor system according to claim 7, wherein the sensing chip further comprises: a substrate; an insulating layer provided on the substrate; a semiconductor layer provided on the insulating layer; a conductive layer covering the A semiconductor layer; a first material layer covering the conductive layer; a second material layer covering the first material layer; and a third material layer covering the second material layer.