BIOFET WITH INCREASED SENSING AREA
The present disclosure provides a bio-field effect transistor (BioFET) and a method of fabricating a BioFET device. The method includes forming a BioFET using one or more process steps compatible with or typical to a complementary metal-oxide-semiconductor (CMOS) process. The BioFET device includes a substrate, a transistor structure, an isolation layer, an interface layer in an opening of the isolation layer, and a metal crown structure over the interface layer. The interface layer and the metal crown structure are disposed on opposite side of the transistor from a gate structure.
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This application claims priority to U.S. Provisional Patent Application No. 61/782,534, filed Mar. 14, 2013, and entitled “BioFET with Increased Sensing Area,” which application is incorporated herein by reference.
FIELDThis disclosure relates to biosensors and methods for forming bio-chips. Particularly, this disclosure relates to bio-chips having biosensors and fluidic devices and methods for forming them.
BACKGROUNDBiosensors are devices for sensing and detecting biomolecules and operate on the basis of electronic, electrochemical, optical, and mechanical detection principles. Biosensors that include transistors are sensors that electrically sense charges, photons, and mechanical properties of bio-entities or biomolecules. The detection can be performed by detecting the bio-entities or biomolecules themselves, or through interaction and reaction between specified reactants and bio-entities/biomolecules. Such biosensors can be manufactured using semiconductor processes, can quickly convert electric signals, and can be easily applied to integrated circuits (ICs) and microelectromechanical systems (MEMS).
Biochips are essentially miniaturized laboratories that can perform hundreds or thousands of simultaneous biochemical reactions. Biochips can detect particular biomolecules, measure their properties, process the signal, and may even analyze the data directly. Biochips enable researchers to quickly screen large numbers of biological analytes for a variety of purposes, from disease diagnosis to detection of bioterrorism agents. Advanced biochips use a number of biosensors along with fluidic channels to integrate reaction, sensing and sample management. BioFETs (biological field-effect transistors, or bio-organic field-effect transistors) are a type of biosensor that includes a transistor for electrically sensing biomolecules or bio-entities. While BioFETs are advantageous in many respects, challenges in their fabrication and/or operation arise, for example, due to compatibility issues between the semiconductor fabrication processes, the biological applications, restrictions and/or limits on the semiconductor fabrication processes, integration of the electrical signals and biological applications, and/or other challenges arising from implementing a large scale integration (LSI) process.
Aspects of the present disclosure are best understood from the following detailed description when read with the accompanying figures. It is emphasized that, in accordance with the standard practice in the industry, various features are not drawn to scale. In fact, the dimensions of the various features may be arbitrarily increased or reduced for clarity of discussion.
It is to be understood that the following disclosure provides many different embodiments, or examples, for implementing different features of the invention. Specific examples of components and arrangements are described below to simplify the present disclosure. These are, of course, merely examples and are not intended to be limiting. Moreover, the formation of a first feature over or on a second feature in the description that follows may include embodiments in which the first and second features are formed in direct contact, and may also include embodiments in which additional features may be formed interposing the first and second features, such that the first and second features may not be in direct contact. Further still, references to relative terms such as “top”, “front”, “bottom”, and “back” are used to provide a relative relationship between elements and are not intended to imply any absolute direction. Various features may be arbitrarily drawn in different scales for simplicity and clarity.
In a BioFET, the gate of a MOSFET (metal-oxide-semiconductor field-effect transistor), which controls the conductance of the semiconductor between its source and drain contacts, is replaced by a bio- or biochemical-compatible layer or a biofunctionalized layer of immobilized probe molecules that act as surface receptors. Essentially, a BioFET is a field-effect biosensor with a semiconductor transducer. An advantage of BioFETs is the prospect of label-free operation. Use of BioFETs avoids costly and time-consuming labeling operations such tagging analytes with fluorescent or radioactive probes.
Binding of a target biomolecule or bio-entity to the gate or a receptor molecule immobilized on the gate of the BioFET modulates the conductance of the BioFET. When the target biomolecule or bio-entity is bonded to the gate or the immobilized receptor, the drain current of the BioFET is varied by the gate potential, which depends on the type and amount of target bound. This change in the drain current can be measured and used to determine the type and amount of bonding between the receptor and the target biomolecule or bio-entity. A variety of receptors may be used to functionalize the gate of the BioFET such as ions, enzymes, antibodies, ligands, receptors, peptides, oligonucleotides, cells of organs, organisms and pieces of tissue. For instance, to detect ssDNA (single-stranded deoxyribonucleic acid), the gate of the BioFET may be functionalized with immobilized complementary ssDNA strands. Also, to detect various proteins such as tumor markers, the gate of the BioFET may be functionalized with monoclonal antibodies.
One example of a biosensor has a sensing surface is a top of a floating gate connected to the gate of the BioFET. The floating gate is connected to the gate structure of the BioFET through a stack of metal interconnect lines and vias (or multi-layer interconnect, MLI). The various metal layers over the gate electrode can also contribute to damage by antenna effect during the MLI formation process. In such a BioFET, the potential-modulating reaction takes place at an outer surface of the final (top) metal layer or a dielectric surface formed on top of the MLI and is sensed indirectly by the BioFET. The sensitivity of the device is lower than other biosensors because of parasitic capacitances associated with the MLI. As result a sensing plate dimension is usually specified so that a sufficiently detectable amount of potential-modulating reaction can take place on the sensing plate. The minimum sensing plate dimension in turn limits the BioFET density.
In another example, the biomolecules bind directly or through receptors on the gate or the gate dielectric of the BioFET. These “direct sensing” BioFETs directly senses the target biomolecules without the parasitic capacitances associated with MLI. Its construction requires removal of the MLI material above the BioFET to form a sensing well that exposes the gate electrode or gate dielectric to the fluidic environment where potential-modulating surface reactions occur. These BioFETs are more sensitive than the floating gate types but are challenging to construct for several reasons. The sensing well etched has a high aspect ratio, for example, 30 or greater, so it is usually performed with high energy plasma etch. The high-aspect ratio of the sensing well also limits the profile of the etched sensing well. The high energy plasma etch can damage the gate electrode due to charge-induced damage. One attempt in reducing the aspect ratio of the sensing well to make the etch easier results in limitation of the number of metal layers, down to one or two metal layers. The reduction in metal layers limits the interconnect routing and integration options of the device, for example, the number and type of circuits for controlling the BioFET. The process is also very sensitive to alignment, because misalignment may expose the metals in the MLI surrounding sensing well or cause the sensing surface area to be smaller than designed.
In yet another example, the biomolecules are placed close to the gate from a backside of the substrate. In this example, a sensing surface is formed on the backside of the transistor gate through backside of the substrate. This example avoids the difficulty of having to etch through multiple layers of interconnects and yet places the biomolecules close enough to the gate to have much higher sensitivity than the floating gate biosensor.
An opening is provided in the isolation layer 110. The opening is substantially aligned with the active region 108. An interface layer 124 is disposed on the bottom of the opening on the surface of the active region 108.
According to various embodiments of the present disclosure, a metal crown structure 126 is disposed over the interface layer 124 and at least partially covering the sidewalls of the opening. The metal crown structure 126 is the sensing surface used to detect biomolecules or bio-entities. Area of the metal crown structure 126 is larger than the interface layer 124 and thus can accommodate more potential modulating reactions. In some embodiments, the metal crown structure 126 extends over the top corners of the opening and partially covers the isolation layer 110. In certain embodiments, a number of receptors are bound or amplified on the metal crown structure 126 to provide sites for detecting biomolecules or bio-entities. In other embodiments, the metal crown structure 126 surface is used to bind biomolecules or bio-entities having particular affinities to the metal material. The metal-containing material for metal crown structure 126 includes tantalum, tantalum nitride, niobium, tungsten nitride, ruthenium oxide, or combinations of these. Other metals including gold and platinum may also be used. According to some embodiments, the material for the metal crown structure 126 is an ohmic metal.
The semiconductor device also includes a fluidic structure 132 over the isolation layer 110 that forms a fluidic channel or well over the metal crown structure 126. During operation, a liquid analyte 130 is flowed into the fluidic channel. The liquid analyte 130 includes target molecules that would bind to the receptors 128 on the metal crown structure 126. The reaction and bound target molecules are sensed by the semiconductor device 100. The semiconductor device 100 includes electrical contacts, shown symbolically and not as a cross section of the actual contact, to the source region 106 (116), the drain region (118), the gate structure 102 (120), and/or the active region 108 (e.g., front gate (FG) 122).
Thus, while a conventional FET uses a gate contact to control conductance of the semiconductor between the source and drain (e.g., the channel), the semiconductor device 100 allows receptors formed on the opposing side of the FET device to control the conductance, while the gate structure 102 (e.g., polysilicon) provides a back gate (e.g., source substrate or body node in a conventional FET). The gate structure 102 provides a back gate that can control the channel electron distribution without a bulk substrate effect. Thus, if molecules attach to receptors provided on the metal crown structure 126, the resistance of the field-effect transistor channel region is altered. In some embodiments, a front gate bias is used instead of a back gate bias. The front gate electrode is located proximate to the sensing surface. Therefore, the semiconductor device 100 may be used to detect one or more specific biomolecules or bio-entities in the analyte environment around and/or in the opening 112.
The semiconductor device 100 may include additional passive components such as resistors, capacitors, inductors, and/or fuses; and other active components, including P-channel field effect transistors (PFETs), N-channel field effect transistors (NFETs), metal-oxide-semiconductor field effect transistors (MOSFETs), complementary metal-oxide-semiconductor (CMOS) transistors, high voltage transistors, and/or high frequency transistors; other suitable components; and/or combinations thereof. It is further understood that additional features can be added in the semiconductor device 100, and some of the features described below can be replaced or eliminated, for additional embodiments of the semiconductor device 100.
The method 200 begins at operation 202 where a substrate is provided. The substrate is a semiconductor substrate. The semiconductor substrate may be a silicon substrate or wafer. Alternatively, the substrate may comprise another elementary semiconductor, such as germanium; a compound semiconductor including silicon carbide, gallium arsenic, gallium phosphide, indium phosphide, indium arsenide, and/or indium antimonide; an alloy semiconductor including SiGe, GaAsP, AlInAs, AlGaAs, GaInAs, GaInP, and/or GaInAsP; or combinations thereof. In various embodiments, the substrate is a semiconductor-on-insulator (SOI) substrate. The SOI substrate may include a buried oxide (BOX) layer formed by a process such as separation by implanted oxygen (SIMOX), and/or other suitable processes. The substrate may be doped, such as p-type and n-type. As used herein, workpiece refers to a substrate together with any material bonded or deposited thereon. The semiconductor substrate (or device substrate) refers to the base material on and in which the devices are built and does not include any deposited or bonded material.
Referring to
After forming the FET on the substrate, a multi-layer interconnect (MLI) structure is formed on the substrate. The MLI structure may include conductive lines, conductive vias, and/or interposing dielectric layers (e.g., interlayer dielectric (ILD)). The MLI structure may provide physical and electrical connection to the transistor. The conductive lines may comprise copper, aluminum, tungsten, tantalum, titanium, nickel, cobalt, metal silicide, metal nitride, poly silicon, combinations thereof, and/or other materials possibly including one or more layers or linings. The interposing or inter-layer dielectric layers (e.g., ILD layer(s)) may comprise silicon dioxide, fluorinated silicon glass (FGS), SILK (a product of Dow Chemical of Michigan), BLACK DIAMOND (available from Applied Materials of Santa Clara, Calif.), and/or other insulating materials. The MLI may be formed by suitable processes typical in CMOS fabrication such as CVD, PVD, ALD, plating, spin-on coating, and/or other processes.
Referring to the example of
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In some embodiments, details of the forming the opening operation includes a number of steps as shown in process diagram of
In operation 254 of
In
In other embodiments, the device substrate is thinned such that the bulk silicon layer is removed, and the buried insulating layer remains on the substrate. The removal of the bulk silicon may be performed using, for example, CMP, HNA, and/or TMAH etching, which stops at the buried insulating layer. The substrate may have a thickness of approximately 500 Angstroms (A) to 1500 A after the thinning process. For example, in one embodiment the active region of an SOI substrate has a thickness of between of approximately 500 A and 1500 A. The buried insulating layer (now providing the surface of the substrate) may be the isolation layer.
In operation 256 of
In operation 258 of
In operation 260 of
In operation 262 of
In operation 264 of
The present disclosure also pertains to embodiments where the electrical connections for the BioFET device are made to the opposite side of the substrate as the fluidic connections. In those embodiments, electrodes and pads are formed connecting to the MLI on the front side of the substrate before the carrier substrate is bonded and device substrate thinned. From the backside, trench 602 is not formed.
Referring back to
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The metal layer is deposited conformally over the substrate and in the opening covering the interface layer. The metal layer may be deposited using a PVD (sputtering), metal chemical vapor deposition (MCVD), atomic layer CVD (ALCVD), electrochemical deposition with a seed layer, or electroless deposition. In some embodiments, an ion beam deposition may be used to selectively deposit the metal layer in and around the opening.
In operation 212, the metal layer is patterned to form a metal crown structure. In some embodiments, the patterning involves removing, by etching, unwanted portions of the metal layer deposited in operation 210. An etch mask is first deposited and patterned. The etch mask may be a photoresist or a hardmask patterned by a photolithography process. In other embodiments, a photoresist material is first deposited and patterned on the substrate and removed after the metal layer is deposited. Lifting off the photoresist material also removes any overlying metal layers. The lift-off technique may be useful when the dry etch involving plasma to remove the metal pattern would cause undesirable amounts of plasma-induced damage to other exposed metal surfaces. Because the photoresist in the lift-off process may be removed with just wet etching or including low-power plasma etching, it is sometimes preferred over the metal patterning technique. However, the lift-off process has the potential to produce more contaminants and a shape of the resulting metal crown structure may include jagged edges.
In the example of
According to various embodiments, the metal crown structure 1202 has a surface area that is about twice as large as the surface area of the interface layer 1102. The larger surface area allows more potential modulating reaction to take place on its surface. However, the area is not so large that significant resistance develops across the metal crown structure. Further, the area is not so large so that a high number of reactions would remove the BioFET from the linear region of the I-V curve into the saturation region. While the gate bias may be changed during operation to ensure that the BioFET stay in the linear region, the reduction in sensitivity and the concomitant increase in analyte concentration would reduce the benefit of the metal crown structure.
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In some embodiments, more than one type of metal crown structure is formed or deposited. Different metal crown structures may mean that the surface areas are different by patterning. Thus measurements from different regions of the transistor IV curve may be compared to determine the analyte concentration. In some examples, different materials are used in different sites. Because the receptors may be designed to have different affinities to different metal crown structure materials, a BioFET device may have several BioFETs configured to detect different biomolecules or bio-entities. For example, some sites may include a tantalum containing metal crown structure and other sites may include a ruthenium oxide containing metal crown structure. A receptor may be designed to have a higher affinity for one or the other of the surfaces. Another receptor may not be selective between the two. By exposing the selective receptor first through the microfluidic channel and wells, bonding sites on the high affinity surface may be occupied before the non-selective receptor is exposed to the surfaces. By designing receptors for different surfaces, a BioFET device can be used to design several biomolecules or bio-entities.
During operation of the BioFET device, a solution that contains target molecules is provided in the fluidic channel. The BioFET device may contain different areas for processing the target molecule. Some bio-material may be lysed, separated, dyed, and otherwise tested or analyzed using chemical, electrical, or optical means. For example, a drop of blood may be inserted in an inlet and initially separated by plasma and cell type. Certain cells in the blood drop may be lysed. Some macromolecules in the lysate may be further broken down for analysis by downstream in the flow path. Deoxyribonucleic acid (DNA) molecules may be fragmented by restriction or shearing into target strands.
After processing the bio-material into targets, the targets are detected by flowing through microfluidic channels and wells containing the BioFETs. The flow may be controlled such that the targets have a long residence time in the presence of the metal crown structure sensing surfaces as compared to the reaction time. In some embodiments, gate bias is varied while the current flown through the BioFET is collected. The electrical information from the BioFET are collected and analyzed.
In various embodiments, a CMOS fabrication facility (e.g., foundry) may process the methods in accordance with various embodiments for the associated device up to the fluidic channel formation. In an embodiment, a subsequent user may provide the surface treatment technologies, ionic solutions, receptors, and the like.
In summary, the methods and devices disclosed herein provide a BioFET that is fabricated using CMOS and/or CMOS compatible processes. Some embodiments of the disclosed BioFET may be used in biological and/or medical applications, including those involving liquids, biological entities, and/or reagents. One detection mechanism of some embodiments described herein includes a conductance modulation of the FET of the BioFET due to the binding of the target bio-molecule or bio-entity to the gate structure, or a receptor molecule disposed (e.g., immobilized) on the gate structure of a device.
Some embodiments of the BioFETs are arranged in an array form. They may include a back-gate for back-gate biasing to improve respond time and/or enhance sensitivity. The gate structures may be built on silicon-on-insulator (SOI) substrates. This may provide advantages in some embodiments of operation at a higher speed and/or consumption of less power. The inverted transistor provided on an SOI substrate may achieve improved fabrication uniformity, have improved process control, and the like. Some embodiments may provide for an improved short-channel effect, for example, due to the formation on a SOI substrate.
Thus, it will be appreciated that in one embodiment a BioFET device is described that includes a substrate, a transistor structure in the substrate, an isolation layer with an opening on a side of the substrate opposite from a gate structure of the transistor, an interface layer in the opening, and a metal crown structure over the interface layer and at least partially covering the sidewalls of the opening. The transistor structure has a gate structure over a source region, a drain region, and a channel region. The opening in the isolation structure is at the channel region of the transistor structure.
One aspect of the present disclosure pertains to a semiconductor device is provided that includes an array of BioFET devices. The array is connected to at least one sense amplifier. A first BioFET device in the array includes a gate structure formed on a substrate, a source region and a drain region formed in the substrate adjacent the gate structure, a channel region interposing the source and drain regions and underlying the gate structure, and an interface layer disposed on the channel region, and a metal crown structure over the interface layer, the metal crown structure having a larger surface area than the interface layer. The interface is disposed on a first side of the channel region and the gate structure is disposed on the opposing, second side of the channel region.
Another aspect of the present disclosure pertains to a method of fabricating a BioFET device includes forming a transistor on a semiconductor substrate and etching an opening in an isolation layer disposed on a second side of the semiconductor substrate to exposes the channel region of the transistor. The transistor includes a gate structure formed on a first side of the semiconductor substrate and a channel region between a source region and a drain region. The method also includes depositing an interface material on the channel region in the opening, depositing a metal layer, and patterning the metal layer to form a metal crown structure.
In describing one or more of these embodiments, the present disclosure may offer several advantages over prior art devices. In the discussion of the advantages or benefits that follows it should be noted that these benefits and/or results may be present is some embodiments, but are not required. Advantages of some embodiments of the present disclosure include the ability to offer a customer-customizable product. For example, fluidic channel formation, receptor introduction and the like may be performed by a customer. The size, shape, and material of the metal crown structure may be customized by the customer. As a further example of advantages of one or more embodiments described herein, in conventional devices it is typical to require high aspect ratio processing to form a bio-compatible interface (e.g., requiring etching from a front surface of the substrate to a gate structure). Because the present methods provide for processing on a backside of a thinned wafer, the aspect ratio is reduced.
Claims
1. A biological field-effect transistors (BioFET) device, comprising:
- a substrate;
- a transistor structure in the substrate having a gate structure over a source region, a drain region, and a channel region;
- an isolation layer on a side of the substrate opposite from the gate structure, said isolation layer having an opening at the channel region of the transistor structure;
- an interface layer in the opening; and,
- a metal crown structure over the interface layer and at least partially covering sidewalls of the opening.
2. The BioFET device of claim 1, wherein the metal crown structure comprises tantalum, tantalum nitride, niobium, tungsten nitride, ruthenium oxide, or combinations of these.
3. The BioFET device of claim 1, wherein the metal crown structure completely covers the sidewalls of the opening.
4. The BioFET device of claim 1, wherein a portion of the metal crown structure covers a portion of the isolation layer.
5. The BioFET device of claim 1, wherein the interface layer comprises a high-k dielectric.
6. The BioFET device of claim 1, wherein the interface layer comprises aluminum oxide, titanium oxide, hafnium oxide, tantalum oxide, or tin oxide.
7. The BioFET device of claim 1, further comprising:
- a fluidic channel disposed on the isolation layer.
8. The BioFET device of claim 1, further comprising:
- a multi-layer interconnect (MLI) disposed in the substrate on a side of the substrate that is same as the gate structure.
9. The BioFET device of claim 8, wherein a carrier substrate is bonded to the substrate via a passivation layer over the MLI.
10. The BioFET device of claim 1, wherein a surface area of the metal crown structure is at least twice of the interface layer.
11. A method of making a biological field-effect transistors (BioFET) device, comprising:
- forming a transistor on a semiconductor substrate, wherein the transistor includes a gate structure formed on a front side of the semiconductor substrate and a channel region between a source region and a drain region;
- etching an opening in an isolation layer disposed on a back side of the semiconductor substrate, wherein the opening exposes the channel region of the transistor;
- depositing an interface material on the channel region in the opening;
- depositing a metal layer on the interface material; and
- patterning the metal layer to form a metal crown structure.
12. The method of claim 11, further comprising forming a multi-layer interconnect (MLI) on the front side of the substrate.
13. The method of claim 11, wherein the isolation layer is an insulator of a silicon-on-insulator (SOI) substrate.
14. The method of claim 11, further comprising:
- thinning the semiconductor substrate; and
- depositing an isolation layer on the back side of the semiconductor substrate.
15. The method of claim 14, wherein the semiconductor substrate is an SOI substrate and the thinning removes a buried oxide layer.
16. The method of claim 11, further comprising:
- binding a receptor on the metal crown structure, wherein the receptor is selected from the group consisting of enzymes, antibodies, ligands, receptors, peptides, nucleotides, cells of organs, organisms and pieces of tissue.
17. A device, comprising:
- a first biological field-effect transistors (BioFET) device, including: a gate structure formed on a substrate; a source region and a drain region formed in the substrate adjacent the gate structure; a channel region interposing the source and drain regions and underlying the gate structure; an interface layer disposed on the channel region, wherein the interface is disposed on a first side of the channel region and the gate structure is disposed on an opposing, second side of the channel region; and a metal crown structure over the interface layer, the metal crown structure having a larger surface area than the interface layer; and
- a sense amplifier coupled to the first BioFET device.
18. The device of claim 17, wherein the metal crown structure comprises multiple layers.
19. The device of claim 17, further comprising:
- a plurality of BioFETs, wherein the plurality of BioFETs are configured in an array.
20. The device of claim 19, wherein at least one of the plurality of BioFETs has a different material in the metal crown structure from at least another one of the plurality of BioFETs.
Type: Application
Filed: Aug 16, 2013
Publication Date: Sep 18, 2014
Applicant: Taiwan Semiconductor Manufacturing Company, Ltd. (Hsin-Chu)
Inventors: Chun-Wen Cheng (Zhubei City), Yi-Shao Liu (Zhubei City), Fei-Lung Lai (New Taipei City)
Application Number: 13/969,160
International Classification: G01N 27/414 (20060101);