CN113130648B - Tumor marker sensor based on fin field effect transistor manufacturing process - Google Patents

Tumor marker sensor based on fin field effect transistor manufacturing process Download PDF

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CN113130648B
CN113130648B CN201911402226.3A CN201911402226A CN113130648B CN 113130648 B CN113130648 B CN 113130648B CN 201911402226 A CN201911402226 A CN 201911402226A CN 113130648 B CN113130648 B CN 113130648B
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tumor marker
film
thickness
marker sensor
sensor
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CN113130648A (en
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魏千惠
张青竹
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GRIMN Engineering Technology Research Institute Co Ltd
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    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01LSEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L29/00Semiconductor devices adapted for rectifying, amplifying, oscillating or switching, or capacitors or resistors with at least one potential-jump barrier or surface barrier, e.g. PN junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof  ; Multistep manufacturing processes therefor
    • H01L29/66Types of semiconductor device ; Multistep manufacturing processes therefor
    • H01L29/68Types of semiconductor device ; Multistep manufacturing processes therefor controllable by only the electric current supplied, or only the electric potential applied, to an electrode which does not carry the current to be rectified, amplified or switched
    • H01L29/76Unipolar devices, e.g. field effect transistors
    • H01L29/772Field effect transistors
    • H01L29/78Field effect transistors with field effect produced by an insulated gate
    • H01L29/785Field effect transistors with field effect produced by an insulated gate having a channel with a horizontal current flow in a vertical sidewall of a semiconductor body, e.g. FinFET, MuGFET
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81BMICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B7/00Microstructural systems; Auxiliary parts of microstructural devices or systems
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81CPROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00015Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
    • B81C1/00023Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
    • B81C1/00119Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01LSEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L29/00Semiconductor devices adapted for rectifying, amplifying, oscillating or switching, or capacitors or resistors with at least one potential-jump barrier or surface barrier, e.g. PN junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof  ; Multistep manufacturing processes therefor
    • H01L29/66Types of semiconductor device ; Multistep manufacturing processes therefor
    • H01L29/66007Multistep manufacturing processes
    • H01L29/66075Multistep manufacturing processes of devices having semiconductor bodies comprising group 14 or group 13/15 materials
    • H01L29/66227Multistep manufacturing processes of devices having semiconductor bodies comprising group 14 or group 13/15 materials the devices being controllable only by the electric current supplied or the electric potential applied, to an electrode which does not carry the current to be rectified, amplified or switched, e.g. three-terminal devices
    • H01L29/66409Unipolar field-effect transistors
    • H01L29/66477Unipolar field-effect transistors with an insulated gate, i.e. MISFET
    • H01L29/66787Unipolar field-effect transistors with an insulated gate, i.e. MISFET with a gate at the side of the channel
    • H01L29/66795Unipolar field-effect transistors with an insulated gate, i.e. MISFET with a gate at the side of the channel with a horizontal current flow in a vertical sidewall of a semiconductor body, e.g. FinFET, MuGFET

Abstract

The invention discloses a tumor marker sensor based on a fin field effect transistor manufacturing process. The tumor marker sensor adopts a nanowire structure formed from top to bottom and compatible with CMOS, and comprises: a Si nanowire formed on the SOI substrate by a fin field effect transistor fabrication process; preparing a gold electrode by photoetching, magnetron sputtering and stripping processes; a high-k gate dielectric layer formed by an atomic layer deposition method is arranged on the surface of the tumor marker sensor; and the microfluidic multichannel is built on the surface of the sensor through a photoetching process and an alignment technology. The tumor marker sensor can be used for quickly, accurately and sensitively detecting the mixed protein solution, and has the advantages of miniaturization, integration, low manufacturing cost, cyclic utilization and the like.

Description

Tumor marker sensor based on fin field effect transistor manufacturing process
Technical Field
The invention relates to a tumor marker sensor based on a fin field effect transistor (FinFET) manufacturing process, and belongs to the technical field of biosensors.
Background
With the rising of the morbidity and mortality of malignant tumors, the malignant tumor becomes the leading cause of death in China and also becomes a public health problem with much attention. Early diagnosis in time and high efficiency can realize early discovery and early treatment of tumors, remarkably improve the survival rate of patients, and is one of the most challenging problems in clinical medicine. Although modern imaging techniques have become an important tool for tumor diagnosis, tumor molecular markers still have irreplaceable clinical application value. The expression of tumor markers (such as nucleic acid, protein, peptide and the like), the variation of gene sequences or the change of cell signal transmission channels and the like existing in serum, plasma, tissues or other body fluids are detected by a molecular technology, so that important scientific judgment basis can be provided for the prevention and control, early diagnosis, curative effect observation, prognosis evaluation and the like of tumors. Domestic and foreign researches prove that the single marker has defects in diagnosing early malignant tumors, and the combination of multiple markers can improve the sensitivity and specificity of diagnosis.
The preparation method based on a Complementary Metal Oxide Semiconductor (CMOS) circuit can detect a plurality of tumor markers such as nucleic acid, protein and the like at a molecular level. The silicon nanowire serving as a novel one-dimensional semiconductor nanomaterial has the unique advantages of ultrahigh sensitivity, specific selectivity, label-free detection, excellent biocompatibility, quick real-time response, compatibility with a large-scale CMOS (complementary metal oxide semiconductor) preparation process and the like, and has attracted great attention in the biomedical detection aspect in recent years. However, most silicon nanowire field effect transistor sensors are manufactured by an electron beam direct writing process, require a support material with a large volume to produce nanowires, are low in yield, high in cost and not suitable for large-scale production, and can cause irreversible damage to cells in a detection process.
Therefore, the development of a tumor marker sensor which has high performance, low cost, high selectivity and high sensitivity and can be produced and processed in a large scale has important significance for early diagnosis of tumors.
Disclosure of Invention
The invention aims to provide a tumor marker sensor based on a fin field effect transistor (FinFET) manufacturing process, which can be used for quickly and accurately detecting more than two marker molecules with high flux and high sensitivity, and has the advantages of miniaturization, integration, low manufacturing cost and the like.
In order to achieve the purpose, the invention adopts the following technical scheme:
a tumor marker sensor based on a fin field effect transistor manufacturing process adopts a CMOS compatible top-down method to form a nanowire structure, and comprises the following steps: a silicon nanowire formed on the SOI substrate by a fin field effect transistor fabrication process; preparing a gold electrode by photoetching, magnetron sputtering and stripping processes; a high-k gate dielectric layer formed by an atomic layer deposition method is arranged on the surface of the biosensor; and the microfluidic multichannel is built on the surface of the sensor through a photoetching process and an alignment technology.
Wherein the high-k gate dielectric layer is HfO2、ZrO2Or Al2O3A layer.
Specifically, the preparation process of the tumor marker sensor comprises the following steps:
(1) reducing the thickness of the top layer silicon to 30nm by sacrificial oxidation and HF corrosion on an SOI (silicon-on-insulator) substrate, and then sequentially depositing SiO on the top layer silicon2Thin film, amorphous Si (alpha-Si) thin film and Si3N4A film;
(2) after the photolithography step, Si is performed3N4Transferring the pattern by a conventional dry etching process of the film and the amorphous Si film, removing the photoresist, and forming a rectangular pattern array;
(3) removal of Si on top of mask array using hot phosphoric acid solution3N4Hard mask, using plasma enhanced deposition of Si with thickness of 30nm3N4The film is subjected to corresponding reactive ion etching to form a side wall pattern;
(4) removal of two Si groups with tetramethylammonium hydroxide3N4Amorphous Si material between the side walls, and then nano-sized Si3N4Side wall hard mask array left in SiO2The top of the film;
(5) after the oxide at the bottom and the ultrathin Si are subjected to a dry etching process, removing the top hard mask by using HF to form a Si nanowire array;
(6) forming a deposited metal pattern by using negative photoresist, and sputtering and depositing a 100nm gold electrode, wherein the length of the gold electrode is 2mm in order to separate the test electrode from the tumor marker solution;
(7) growing a high-k gate dielectric layer on the surface of the tumor marker sensor by an Atomic Layer Deposition (ALD) method;
(8) the dual-channel micro-fluidic pipeline is prepared by a photoetching method, and the micro-fluidic pipeline is aligned with the sensor so that the tumor marker can pass through the sensitive area.
Wherein, in the step (1), SiO2The thickness of the film is 30-50nm, the thickness of the amorphous Si (alpha-Si) film is 50-150nm, and Si3N4The thickness of the film is 10-50 nm. Preferably, SiO2The thickness of the film is 30nm, the thickness of the amorphous Si film is 100nm, and Si3N4The thickness of the film was 30 nm.
In the step (6), the gold electrode is Ti/Au, Pd/Au or Ni/Au, wherein the thickness of the adhesion layer is 5-30nm, and the thickness of the conductive layer such as gold is 50-200 nm.
In the step (7), the thickness of the high-k gate dielectric layer is 5-20 nm.
The invention has the beneficial effects that:
1. the tumor marker sensor is manufactured by the traditional mainstream FinFET process, and is easy to realize low cost and industrialization.
2. The concentration level of the marker is reflected by real-time monitoring of the current, and the basic quantitative detection of the tumor marker is realized.
3. The discrimination of the test is improved by different surface modification antibodies, more than two tumor markers are simultaneously and multichannel detected, and the accuracy of early diagnosis of the tumor is improved.
Drawings
FIG. 1 is a top view of a tumor marker sensor of the present invention.
FIG. 2 is a graph of AFP and GGT2 sensor leakage current over time in an example.
Detailed Description
The present invention is further described in detail below with reference to the drawings and examples, but the scope of the present invention is not limited thereto.
As shown in fig. 1, the tumor marker sensor of the present invention employs a CMOS compatible "top-down" formed nanowire structure, which specifically includes: an SOI substrate 1; si nanowire 2 and gold electrode 3 formed on the SOI substrate; a high-k gate dielectric layer 4 is formed on the surface of the sensor; a microfluidic multi-channel 5 is set up above the tumor marker sensor. Wherein, the high-k gate dielectric layer can be HfO2、ZrO2Or Al2O3And (3) a layer.
In one embodiment of the present invention, the method for manufacturing a tumor marker sensor includes the steps of:
(1) forming a thick top layer of silicon on an SOI (silicon-on-insulator) substrate by sacrificial oxidation and HF etchingThinning the thickness to 30nm, and then sequentially depositing SiO on the top layer silicon2Thin film, amorphous Si (alpha-Si) thin film and Si3N4A film;
(2) in the presence of Si3N4Carrying out photoetching after the conventional dry etching process of the film and the amorphous Si film, transferring the pattern by etching, and removing the photoresist to form a rectangular mask array;
(3) removal of Si on top of mask array using hot phosphoric acid solution3N4Hard mask, using plasma enhanced deposition of Si with thickness of 30nm3N4Carrying out corresponding reactive ion etching on the film to form a side wall pattern;
(4) removal of two Si groups with tetramethylammonium hydroxide3N4Amorphous Si material between the side walls, and then nano-sized Si3N4Side wall hard mask array left in SiO2The top of the film;
(5) SiO of the bottom2After the ultrathin top layer Si is subjected to a dry etching process, removing the top hard mask by using HF to form a Si nanowire array;
(6) forming a deposition metal pattern by using a negative photoresist, and sputtering and depositing a gold electrode with the thickness of 100nm, wherein the length of the gold electrode is 2mm in order to separate the test electrode from the marker solution;
(7) and growing a high-k gate dielectric layer on the outer surface of the tumor marker sensor by an atomic layer deposition method (ALD method).
When the tumor marker sensor is used, two different antibodies are coupled in different microfluidic channels through glutaraldehyde and 3-Aminopropyltriethoxysilane (APTES), and the sensor is placed in a protein mixed solution detection environment; the protein solution to be detected and different antibodies in the channel form antigen-antibody combination to be adsorbed on the surface of the sensor, and the change of the potential or current generated by the sensor is recorded. Because the protein and the molecule both have certain charges, when the protein is combined with the corresponding antibody, the change of an electric field or electric potential is generated on the surface of the sensor, the change of the protein level combined with the antibody can be detected by detecting the change of the current of the sensor, and then the analysis and calculation are carried out by a data processing system, so that the information of medical diagnosis and the like with different protein concentration levels can be obtained.
Examples
The tumor marker sensor with the structural characteristics shown in figure 1 is prepared by the method, wherein the length of the silicon nanowire is about 50 mu m, and the width of the silicon nanowire is about 30 nm. The length of the gold electrode is 2mm, the width of the gold electrode is 100 mu m, the space between the electrodes is 30 mu m, and the high-k gate dielectric layer is HfO2A layer having a thickness of 10 nm.
A mixed solution of 50ng/mL alpha-fetoprotein (AFP) solution and 100ng/mL gamma-glutamyltranspeptidase-2 (GGT2) was prepared, 1. mu.L of the mixed solution was dropped into the inlet of the microfluidic channel, negative pressure was applied to the outlet to allow the mixed protein solution to slowly flow through the silicon nanowire region, and the detection electric signal was recorded using a Keithley 4200 semiconductor analyzer. The resulting electrical signals are shown in FIG. 2, with leakage current signals for AFP and GGT2 represented by black and gray curves, respectively. With the mixed solution injected into the micro-channel nanowire reaction area, the current is increased from pA quantity level to about 1nA, which shows that AFP and GGT2 are respectively combined with corresponding antibodies to cause the change of the surface charge of the sensor, thereby influencing the magnitude of the nanowire current.

Claims (5)

1. A tumor marker sensor based on a fin field effect transistor manufacturing process is characterized in that the tumor marker sensor adopts a CMOS compatible 'top-down' method to form a nanowire structure, and comprises the following steps: a silicon nanowire formed on the SOI substrate by a fin field effect transistor fabrication process; preparing a gold electrode by photoetching, magnetron sputtering and stripping processes; forming a high-k gate dielectric layer on the surface of the sensor by an atomic layer deposition method; a microfluidic multichannel is built on the surface of the sensor through a photoetching process and an alignment technology; the preparation process of the tumor marker sensor comprises the following steps:
(1) reducing the thickness of the top layer silicon to 30nm on an SOI substrate by a sacrificial oxidation and HF corrosion method, and then sequentially depositing SiO on the top layer silicon2Thin film, amorphous Si thin film and Si3N4A film;
(2) after the photolithography step, Si is performed3N4Transferring the pattern by a conventional dry etching process of the film and the amorphous Si film, removing the photoresist, and forming a rectangular pattern array;
(3) removal of Si on top of mask array using hot phosphoric acid solution3N4Hard mask, using plasma enhanced deposition of Si with thickness of 30nm3N4Carrying out corresponding reactive ion etching on the film to form a side wall pattern;
(4) removal of two Si groups with tetramethylammonium hydroxide3N4Amorphous Si material between the side walls, and then nano-sized Si3N4Side wall hard mask array left in SiO2The top of the film;
(5) after the oxide at the bottom and the ultrathin Si are subjected to a dry etching process, removing the top hard mask by using HF to form a Si nanowire array;
(6) forming a deposited metal pattern by using negative photoresist, and sputtering and depositing a gold electrode with the thickness of 100nm, wherein the length of the gold electrode is 2mm in order to separate the test electrode from the tumor marker solution;
(7) growing a high-k gate dielectric layer on the surface of the tumor marker sensor by an atomic layer deposition method;
(8) the dual-channel micro-fluidic pipeline is prepared by a photoetching method, and the micro-fluidic pipeline is aligned with the sensor so that the tumor marker can pass through the sensitive area.
2. The tumor marker sensor of claim 1, wherein the high-k gate dielectric layer is HfO2、ZrO2Or Al2O3And (3) a layer.
3. The tumor marker sensor according to claim 1, wherein in the step (1), SiO is2The thickness of the film is 30nm, the thickness of the amorphous Si film is 100nm, and Si3N4The thickness of the film was 30 nm.
4. The tumor marker sensor according to claim 1, wherein in the step (6), the gold electrode is Ti/Au, Pd/Au or Ni/Au, wherein the thickness of the adhesion layer material is 5-30nm and the thickness of the conductive layer Au is 50-200 nm.
5. The tumor marker sensor according to claim 1, wherein in step (7), the thickness of the high-k gate dielectric layer is 5-20 nm.
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