Patent Publication Number: US-2022236214-A1

Title: Semiconductor Device Providing a Biosensor to Test for Pathogen

Description:
CLAIM TO DOMESTIC PRIORITY 
     The present application is a continuation-in-part of U.S. patent application Ser. No. 17/158,609, filed Jan. 26, 2021, which application is incorporated herein in its entirety by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates in general to a semiconductor device and, more particularly, to a semiconductor device and method providing a biosensor to test for a pathogen. 
     BACKGROUND OF THE INVENTION 
     In the field of public health, as performance analyses and medical diagnoses advance, sensors such as biosensors become essential. Biosensors are capable of detecting, proteins, such as antigens and antibodies and deoxyribonucleic acid (DNA), which are all deeply involved in the phenomena of life. 
     The flu has been around for more than 100 years and remains a deadly virus. While the flu today is managed through flu shots every winter, thousands of people die each year from the flu in the United States of America. SARS-COV-2 has proven to be more deadly than the flu by at least by an order of magnitude and as the SARS-COV-2 virus could persist for many years and, even if SARS-COV-2 is eradicated, other diseases are almost certain to occur in the future. 
     In recent history, global travel reaches a wide population with air travel bringing people together within a day or two across the globe. Yet, with all the benefits of global travel come some disadvantages. Perhaps the biggest disadvantage is that an outbreak of disease, such as the novel coronavirus or COVID 19, can spread around the world as fast as infected people can travel. The world population lives in a new era where pandemics are here and will likely alter the course of every aspect of life. As it is certain that people will continue air travel, technologists and scientists need to harness their skills and apply scientific principles to ideas that can engineer a way to aid countries, companies, and individuals on a path back to a quality of life approaching that of a pre-pandemic world. 
     To live in a pandemic world, a major concern will be test availability and test accuracy. The novel coronavirus itself is very small about one micrometer in diameter and now causes scientists to think of ways to defend humankind against a very tiny viral speck that has caused great economic and social damage to humankind. The polymerase-chain-reaction (PCR) swab test, involving a nasopharyngeal swab, is the standard, most reliable diagnostic method. Chemicals are used to amplify the virus&#39;s genetic material from the swab so that it can be analyzed. The test sample goes through a number of cycles in the lab before enough virus is recovered. Yet, swab-type coronavirus diagnostic tests can be inaccurate. A false positive result erroneously labels a person infected, with consequences including unnecessary quarantine and contact tracing. False negative results are more consequential, because infected persons who might be asymptomatic may not be isolated and can infect others. Nasal-swab type detection tests have been used to diagnose suspected cases at a clinic or hospital, where test results take anywhere from 15 minutes to 8 hours. 
     With the threat of the novel SARS-COV-2 coronavirus concerning health officials globally, there is urgent need for better methods of mass screening to contain the spread of the virus. Scanning foreheads of individuals for fever is widely used for screening, but temperature scanning cannot detect asymptomatic infections, nor can it distinguish the novel coronavirus from other respiratory illnesses. Swab-type coronavirus detection tests are slow and inefficient, making them impractical for mass screening, such as schools, workplaces, universities, and entertainment and sports venues. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates a single SARS-COV-2 viral particle; 
         FIGS. 2 a -2 c    illustrate testing for a pathogen using nanopipette; 
         FIGS. 3 a -3 d    illustrate plasma enhanced chemical vapor deposition; 
         FIGS. 4 a -4 d    illustrate forming a silicon on insulator wafer; 
         FIGS. 5 a -5 l    illustrate a process of forming a semiconductor biosensor with an SOI MEMS structure; 
         FIG. 6  illustrates the biosensor test for a pathogen; and 
         FIG. 7  illustrates a current detection circuit to test for the pathogen. 
     
    
    
     DETAILED DESCRIPTION OF THE DRAWINGS 
     The present invention is described in one or more embodiments in the following description with reference to the figures, in which like numerals represent the same or similar elements. While the invention is described in terms of the best mode for achieving the invention&#39;s objectives, it will be appreciated by those skilled in the art that it is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims and their equivalents as supported by the following disclosure and drawings. 
       FIG. 1  is a single SARS-COV-2 viral particle  10  with E protein  12 , spike (S) protein  14 , and M protein  16  extending from envelope  18 . Cells are the basic units of all living organisms that can independently exist. Any attack on the human cells in your body may become life threatening. The SARS-COV-2 is the virus that causes COVID-19 and can only be seen through a transmission electron microscope (TEM). Under a TEM image, SAR-COV-2 has a crown-like appearance, hence the name coronavirus comes from the Latin word “coronam” or “corona”. 
     During the infection process, the SARS-COV-2 virus particle  10  attacks the host&#39;s cells by attaching to receptors ACE2 in the host cell. S proteins  14  bind the virus to the surface of the cellular wall. When conditions are right, SARS-COV-2 virus particle  10  infiltrates the living host cell. Once inside the cell, SAR-COV-2 virus  10  enlists the infected cell to produce RNA and proteins. The virus takes over the cell&#39;s reproductive systems and can copy coronavirus RNA in bulk. The RNA tells the cell how to make viral proteins. The viral proteins are used to build a new generation of coronaviruses within the cell. The new released viruses travel in special compartments to leave the cell and infect adjacent healthy cells, while remaining coronaviruses can replicate within the parent cell attacking the parent cell until eventually destroying the host cell. The replication continues through every cell entered causing eventual destruction of the human cell structure until the virus is rendered inactive by host antibodies, medical intervention, or death of the host. 
     Given the challenges of the SARS-COV-2 virus and the cost of responding to the virus in a pandemic world, there is a need for faster and more accurate diagnostic testing that can be cost effectively applied worldwide. A rapid acceleration of diagnostics test (RADx) has been proposed that could potentially test 100&#39;s of millions of people per day. In one embodiment, RADx is based on nanopipette principles and implemented using scalable silicon on insulator micro electromechanical system (SOI MEMS) semiconductor manufacturing technology. Nanopipettes can uniquely identify biomolecules, such as proteins, based on differences in size, shape, and electrical charge. These differences are determined by the detection of ionic current as proteins interact with the nanopipette tip coated with probe molecules. The antibody-antigen reaction in the sample solution causes a change in the surface charge as a result changing the conductivity of the solution. That change in conductivity measures the concentration of the target SARS-COV-2 and provides a measurement proportional to the viral load of the nanoparticles infecting the human cells. 
       FIG. 2 a    illustrates a simplified technique using nanopipettes and current spectroscopy to detect to the target SARS-COV-2 virus. Nanopipette  50  is partially immersed in electrolyte/analyte solution  52 , e.g., potassium chlorine (KCl), contained within vessel  54 . Nanopipette  50  includes electrode  56  also partially immersed in electrolyte/analyte solution  52 . Electrode  56  is connected to the inverting input of low noise amplifier  58 . The non-inverting input of amplifier  58  receives a reference voltage V REF . Resistor  60  is connected between the output of amplifier  58  and its inverting input to set the gain of the amplifier. The output of amplifier  58  is routed through an analog-to-digital converter to a computer system (not shown) to analyze the measurements. Electrode  62  is partially immersed in electrolyte/analyte solution  52  and connected to ground terminal  64 . Amplifier  58  measures the current at the tip of nanopipette  50 , i.e., changes in current measures concentration of the target. 
     Nanopipette  50  has tip orifices on the order of tens to hundreds of nanometers (nm). Nanopipette  50  makes nanofabrication possible at liquid/solid interfaces. The technology is being applied to COVID-19 detection in an antibody/antigen reaction causing a change in the surface charge resulting in changes in the conductivity of the sample solution that can be directly related to COVID-19 detection. 
     To implement an SOI MEMS nanopipette, atomic level deposition (ALD) deposits alumina or aluminum oxide on inner wall  68  of nanopipette  50  and along the backside of the membrane acting as an electrode that is in intimate contact with solution  52  where the specific antibodies for SARS-COV-2 reaction solution reside. SARS-COV-2 has a positive charge and the antibody reagent solution has a negative charge. The antibodies are attracted to the alumina electrode on the backside of the membrane. Alumina also serves as a way to narrow the thickness of nanopipette  50  so that the sample nasal fluid, saliva, or other biofluids containing SARS-COV-2 is in contact with the reaction group (a binder reference buffer solution) that selectively reacts with the specific SARS-COV-2 particle on the alumina electrode causing a change in electrical current that can be measured accompanying the chemical reaction that takes place when the antibodies combine with the SARS-COV-2 particle. The alumina electrode directly detects the change in electrical current caused by a change in impedance due to the chemical reaction. 
     Window  66  illustrates an exploded view of inner wall  68  of nanopipette  50  with probes  70  extending from the inner wall. Nanopipette  50 , including inner wall  68  and probes  70 , is surrounded by a sample of nasal fluid, blood, saliva, or other biofluids, potentially containing particles of coronavirus  72 . An electrical current flows through the probe tip causing particles of coronavirus  70  to emit an electronic charge. The charged particle  72  is attracted to probe  70  and causes a change in electrical current that is proportional to the amount of coronavirus in the sample. The current spectroscopy measures the change of charge on the nanopipette sensor tip caused by coronavirus particles.  FIG. 2 b    illustrates SARS-COV-2 virus  72  attaching to probes  70  with the direction of current as arrow  74 .  FIG. 2 c    illustrates SARS-COV-2 virus  72  attaching to probes  70  with the direction of current as arrow  76 . 
     Probes  70  immobilized by SARS-COV-2 virus can be implemented on SOI-MEMS-ALD manufacturable alumina nanopipette electrode tip. The nanopipette manufactured using deep reactive ion etching to create the nanocores and atomic level deposition precisely control the diameter of the nanocores and the thickness of the electrode on the backside of the membrane. The DRIE etch process leaves a scalloped side wall that can cause a problem for the flow of the nasal fluid, blood, saliva, or other biofluids through the nanopipette. To avoid this issue a sacrificial thermal oxide is grown on the inner wall of the nanopipette and then removed by wet chemistry following by hydrofluoric acid (HF) vapor phase fuming to smooth the inner wall. Then the atomic level deposition of a material such as alumina or any other material that enhances wetting of the nasal fluid, blood, saliva, or other biofluids through the nanopipette in addition to precisely controlling the diameter of the nanocores and thickness of the electrode on the backside of the membrane. The removal of these inner wall scallops is important to the surface chemistry that enables an electrical signal to be generated that is directly proportional to the viral load. 
       FIGS. 3 a -3 d    illustrate plasma enhanced chemical vapor deposition (PECVD) ALD where a vapor phase is capable of producing thin films of a variety of materials. Based on sequential, self-limiting reactions, ALD offers exceptional conformality on high-aspect ratio structures, thickness control at the angstrom level, and tunable film composition. In  FIG. 3 a   , precursors  80  flow into chamber  82 .  FIG. 3 b    shows plasma creating a mix of positive and negative species of precursors  80 .  FIG. 3 c    shows how species absorb on surface  84  of chamber  82  and react.  FIG. 3 d    shows thin film  86  growing and byproducts  88  released in the direction of arrow  90 . 
     In addition to using ALD to control the nanopipette thickness, ALD is later used to make the nanopipette functional in wafer form. Once the SOI-MEMS-ALD nanopipette has been fabricated in wafer form where up to tens of thousands of non-functional biosensor die are on the wafer it is then made functional by introduction of the reagent buffer solution in vapor phase into each nanopipette nanocore and cavity using atomic level vapor phase deposition using the same principle described in Alumina deposition of  FIGS. 3 a -3 d   . This provides for the mass functionalization of nanopipettes a MEMS wafer level manufacturing and eliminates the manual functionalization of each nanopipette and the associated surface chemistry contamination risk from manual operation. 
       FIG. 4 a    illustrates base substrate wafer  102 , such as silicon, germanium, aluminum phosphide, aluminum arsenide, gallium arsenide, gallium nitride, indium phosphide, silicon carbide, or other bulk semiconductor material. Base substrate wafer  102  has a thickness of 300-500 micrometers (μm) and is prepared by grinding and polishing. In  FIG. 4 b   , buried oxide layer  104  is formed over base substrate wafer  102  by high temperature thermal growth. Buried oxide layer  104  contains one or more layers of silicon dioxide (SiO 2 ), silicon nitride (Si 3 N 4 ), silicon oxynitride (SiON), tantalum pentoxide (Ta 2 O 5 ), aluminum oxide (Al 2 O 3 ), and other material having similar insulating and structural properties. In  FIG. 4 c   , device layer  106  is joined by high temperature fusion bonding or other direct wafer bonding (DWB). In DWB, device layer  106  is first bonded to base substrate wafer  102  at room temperature using macroscopic short-range surface forces. Next, device layer  106  and base substrate wafer  102  are heated to form strong primary bonds at the interface. The DWB process is attractive, as it allows high-strength bonds that are stable at high temperatures to be formed without the introduction of a bonding interlayer or the application of clamping loads during thermal treatment. DWB is particularly useful in the manufacture of MEMS. Device layer  106  can be silicon, germanium, aluminum phosphide, aluminum arsenide, gallium arsenide, gallium nitride, indium phosphide, silicon carbide, or other bulk semiconductor material.  FIG. 4 d    shows SOI wafer  110  including base semiconductor wafer  102 , buried oxide layer  104 , and device layer  106 . SOI wafer  110  undergoes device preparation including high precision grinding and polishing. In one embodiment, SOI wafer  110  has a width or diameter of 100-450 millimeters (mm) and thickness of about 0.4 to 1.0 mm. 
       FIGS. 5 a -5 l    illustrate formation of a biosensor using SOI MEMS, DRIE, and ALD techniques to make a semiconductor device capable of detecting a pathogen.  FIG. 5 a    illustrates a portion of SOI wafer  110  including base semiconductor wafer  102 , buried oxide layer  104 , and device layer  106 . In  FIG. 5 b   , surface  114  of base semiconductor wafer  102  is cavity-SOI etched to form cavity or opening  116  extending through the base semiconductor wafer to buried oxide layer  104  using deep reactive ion etching (DRIE). The DRIE is a highly anisotropic etch process used to create deep penetration, steep-sided holes, cavities, and trenches in wafers/substrates, typically with high aspect ratios. To create deep anisotropic etching of silicon, the etch process switches between different plasma chemistries to provide fluorine-based etching of the silicon while protecting the sidewall of the growing feature with a fluorocarbon layer. A C 4 F 8  plasma deposits a fluoropolymer passivation layer onto the mask and into the etched feature. A bias from the platen causes directional ion bombardment resulting in removal of the fluoropolymer from the base of the feature and the mask. The fluorine free radicals, in the SF 6  plasma, etch the exposed silicon at the base of the etch feature isotropically. The DRIE process repeats multiple times to achieve a vertical etch profile for cavity  116 . A backside wet etch stopping on buried oxide layer  104  is also an advantage of SOI wafer  110 . Buried oxide removal by wet or vapour HF allows the structure in  FIG. 5 b    to be highly manufacturable. 
     In  FIG. 5 c   , surface  120  of device layer  106  is photoresist stripped and cleaned. The thickness of device layer  106  is reduced to about 5 μm. 
     In  FIG. 5 d   , the portion of device layer  106  spanning across cavity  116  is referred to as membrane  128 . Openings  130  are formed through the membrane portion of device layer  106  using front side aperture photolithograph with 2 μm critical dimension and DRIE. Openings  130  extend to cavity  116 . The processing features of DRIE can form openings  130  at 1 μm or less in diameter. SOI wafer  110  is particularly useful as buried layer  104  stops DRIE from the top and bottom surfaces of the wafer. The DRIE etch process can leave a scalloped sidewall that can cause a problem for the flow of the nasal fluid, blood, saliva, or other biofluids through the nanopipette. 
     In  FIG. 5 e   , a sacrificial thermal oxide layer  132  is grown on sidewalls  134  of openings  130 . In  FIG. 5 f   , the sacrificial thermal oxide layer  132  is removed by wet chemistry following by HF vapor phase fuming to smooth the inner wall. Another sacrificial thermal oxide layer  132  is again grown on sidewalls  134  of openings  130 , as shown in  FIG. 5 e   . The sacrificial thermal oxide layer  132  is again removed by wet chemistry following by HF vapor phase fuming to smooth the inner wall, as shown in  FIG. 5 f   . The process of repetitive growth of thermal oxide and removal continues multiple times, in accordance with  FIGS. 5 e -5 f   , until the sidewall of opening  130  is smooth. The smooth sidewalls  134  make opening  130  hydrophilic promoting wetting to the surface, as opposed to Hydrophobic. By eliminating the scalloping from the DRIE etch and using the sacrificial thermal oxide followed by HF fuming or any oxide and silicon etches, sidewall  134  can be smoothed to a tapered form. 
     The smoothing process of  FIGS. 5 e -5 f    can be shown Table 1 as: 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Sidewall smoothing process 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 DRIE trench etch 
                   
               
               
                   
                 Ashing 
               
               
                   
                 Trench etch - post clean 1 
                 SPM (H2SO4 + H2O2) 
               
               
                   
                 Trench etch - post clean 2 
                 BHF 20″ 
               
               
                   
                 N column imp - pre clean 
                 SC1 + DHF + SC2 
               
               
                   
                 N column imp 
               
               
                   
                 N column imp - post clean 
                 SPM (H2SO4 + H2O2) 
               
               
                   
                 N column drive-in - pre clean 
                 SC1 + DHF + SC2 
               
               
                   
                 N column drive-in 
                 Oxide thickness 640 A 
               
               
                   
                 N column wet etch 
                 5% HF: 10′ + S/D 
               
               
                   
                 P column imp - pre clean 
                 DHF + IPA 
               
               
                   
                 P column imp 
               
               
                   
                 P column imp - post clean 
                 SPM (H2SO4 + H2O2) 
               
               
                   
                 P column drive-in - pre clean 
                 SC1 + DHF + SC2 
               
               
                   
                 P column drive-in 
                 Oxide thickness 630 A 
               
               
                   
                 Trench pad -OX - pre clean 
                 SC1 + DHF + SC2 
               
               
                   
                 Trench pad -OX 
                 1000 C., wet 4400 ± 400 A 
               
               
                   
                   
               
            
           
         
       
     
     The asking step and trench etch post clean 1 step provide photoresist and contamination removal. The trench etch post clean 2 step provides for removal of O3TEOS on SiN at about 700 angstroms (A). The N column implant (imp)—pre clean step provides cleaning prior to implant. The N column imp—post clean step removes contamination after implant. The N column drive-in—pre clean step provides cleaning prior to diffusion. The N column wet etch step removes oxide film from N column drive-in. The P column imp—pre clean step cleans isopropyl alcohol (IPA) dry. The P column imp—post clean step removes contamination after implant. The P column drive-in—pre clean step provides cleaning for diffusion. Trench pad—OX—pre clean step provides cleaning for diffusion. Trench pad—OX step improves occurrence of crystal defect after tetraethyl orthosilicate (TEOS) deposition. 
     The removal of the inner sidewall scallops is important to the surface chemistry that enables an electrical signal to be generated that is directly proportional to the viral load. A continuous current should be able to flow through the core without high resistance presented by the sidewall of the core itself due to scallops obstructing flow of fluid. Core  140  should be tapered with the wider portion proximate to surface  120 , and the narrower portion proximate to cavity  116 . An opposite taper is also possible. 
     Returning to  FIG. 5 g   , a layer of material  136  is deposited on sidewalls of cavity  116 , backside surface  138  of membrane  128 , and on sidewalls of openings  130  using ALD. In one embodiment, layer of material  136  is alumina or aluminum oxide (Al 2 O 3 ). Alternatively, layer of material  136  can be any material that enhances wetting of the nasal fluid, blood, saliva, or other biofluids through core  140 , in addition to precisely controlling the diameter of the core and thickness of the electrode on the backside of the membrane.  FIG. 5 h    provides closer detail of membrane  128 . Core  140  is defined as the pathway through membrane  128  with alumina  136  on the sidewalls of openings  130 . Core  140  functions similar to nanopipette  50 . A biofluid sample will be deposited on surface  144  of membrane  128 . A portion of the biofluid sample travels through core  140  to cavity  116  which will contain the antibody reagent solution. The ALD process allows the diameter of core  140  to be highly controlled ranging from 50 nm to 2.0 which in turn controls the amount of biofluid sample passing through the core to cavity  116 . The ratio of the span of membrane  128  to the thickness of the membrane is about 5:1 to provide robustness for the pathogen testing process. The thickness of membrane  128  ranges from 2-20 μm. In one embodiment, the span of membrane  128  is 25 μm and the thickness of the membrane is 5 μm. The shape and dimensions of core  140  are important to the accuracy and performance of the biosensor. The combination of DRIE in forming openings  130  and ALD of alumina to precisely set the diameter of core  140  provides a controllable and repeatable SOI MEMS manufacturing process. 
     The core thickness is related to the current flow and desired to be less than 400±20 nanometers (nm). ALD provides a close tolerance on core thickness by depositing an electrical insulator on sidewall of the core to control thickness and provide electrical isolation, hydrophilic property, and conformal coating. 
     In  FIG. 5 i   , CSOI backside contact  150  is formed over surface  114  of base substrate  102  using DWB. In another embodiment, CSOI backside contact  150  is performed after cavity  116  is formed in base substrate wafer  102 . SOI  110  and membrane  128  are formed after CSOI backside contact  150  is formed. CSOI backside contact  150  includes port  154  to fill cavity  116  with antibody reagent solution post manufacturing. 
     In  FIG. 5 j   , vias are formed from surface  120  through device layer  106  and base substrate wafer  102  to CSOI backside contact  150 . The vias are filled with doped polysilicon or other conductive material to form through conductive silicon vias (TSV)  158   a  and  158   b . Alternatively, TSVs  158   a - 158   b  can be metal pillars, such as Cu. Electrically conductive layers  160 ,  162 , and  164  are formed over surface  120  using PVD, CVD, electrolytic plating, electroless plating process, or other suitable metal deposition process. Conductive layers  160 ,  162 , and  164  can be one or more layers of aluminum (Al), copper (Cu), tin (Sn), nickel (Ni), gold (Au), silver (Ag), or other suitable electrically conductive material. Conductive layer  160  makes electrical connection to TSV  158   a . Conductive layer  162  makes electrical connection to TSV  158   b . Conductive layer  164  makes electrical connection through device layer  106  to the antibody reagent solution in cavity  116 . Accordingly, TSV  158  provide electrical connection between the front side and backside of biosensor  172 . 
     Membrane  128 , which is the span of device layer  106  above reagent cavity  116 , is formed using direct wafer bonding silicon on oxide (SOI) and serves as a structural member to make the device more robust. The membrane alumina-lined SOI can also have silicon hexagonal posts created by photolithogrpahy and DRIE etch that further supports the membrane at various locations across the cavity at a low density not to impact the microfluidic flows of reagent solution when converted from vapor phase to liquid solution.  FIG. 5 k    shows an embodiment with silicon posts or pillars  170  disposed in cavity  116  to provide additional support for membrane  128 . 
       FIG. 5 l    is a top view of biosensor  172  with membrane  128 , cores  140 , and conductive layers  160 - 164 . 
     Biosensor  172  can be used to test for a variety of pathogens. In one embodiment, the pathogen to be tested is the SARS-COV-2 virus. Biosensor  172  is based in part on SOI MEMS technology, and in particular uses DRIE to create openings and ALD to form alumina within those openings. DRIE and ALD provides precise control and repeatable manufacturability over the shape and size of core  140  in membrane  128 , which are key to accurate and efficient testing. 
     Biosensor  172  is typically sent post manufacturing to a lab or medical facility to inject the desired antibody reagent solution through port  154  and into cavity  116 . The antibody reagent solution is selected according to the pathogen to be detected. For example, the antibody reagent solution may be selected that reacts with the specific SARS-COV-2 particle. Biosensor  172  can be configured to detect other pathogens by selection of the corresponding antibody reagent solution. However, the medical facility injecting the desired antibody reagent solution manually into every biosensor port  154  and cavity is a very slow process to functionalize the biosensor. The use of a sacrificial thermal oxide grown on the inner wall of the nanopipette and then removed by wet chemistry followed by HF vapor phase fuming to smooth inner wall provides the microfluidic control of the target sample enabling sensitivity and accuracy. The application of ALD to control the diameter of the nanocore plus the use of atomic level vapor phase deposition of the reagent buffer solution to mass functionalize each nanopipette in wafer form makes this a novel high volume mass production worthy technology. 
     Biosensor  172 , loaded with the antibody reagent solution that reacts with the SARS-COV-2, can be sent to the field for testing purposes.  FIG. 6  illustrates testing on human subject  200  using biosensor  172 . Nasopharyngeal test swab  204  is taken from nasal cavity  206  of human subject  200 . Test swab  204  contains biofluid  202 . Test swab  204  with biofluid  202  is inserted into opening  208  of test unit  210 . Test unit  210  is a one-time use, disposable cartridge. Test unit  210  contains biosensor  172  and includes electrical connector  212 , which is connected to conductive layers  160 ,  162 , and  164  on biosensor  172 . Electrical connector  212  is inserted into electrical receptacle  218  of tester  220 . Placing test swab  204  in opening  208  causes biofluid  202  to be deposited on surface  144  of membrane  128 . Accordingly, a sufficient amount of biofluid  202  to perform the test is deposited on surface  144  of membrane  128 . Biofluid  202  can be nasal fluid, saliva, blood, and other bodily fluids. Biofluid  202  is drawn through core  140  and introduced into cavity  116  to mix with the antibody reagent solution. Alumina  136 , as deposited by ALD on inner walls of hole  130  and on surface  138  inside cavity  116 , controls the width of core  140  to pass a known amount of biofluid  202  to react with the antibody reagent solution. If present, SARS-COV-2 virus particles bond with the antibody reagent solution specifically selected for such reaction, i.e., SARS-COV-2 test. Alumina  136  acts as an electrode host that is in intimate contact with the antibody reagent solution. These antibodies are attracted to the alumina electrode host in core  140  and on surface  138  of membrane  128 . An ionic current is generated as SARS-COV-2 virus particles interact with the antibody reagent solution along the alumina electrode host in core  140  and on surface  138  of membrane  128 . The SARS-COV-2 virus particles chemically reacting with the antibody reagent solution, i.e., antibodies combining with SARS-COV-2, changes the impedance in the ionic current path. The antibody-antigen reaction in the sample solution causes a change in the surface charge as a result changing the conductivity of the solution. That change in conductivity measures the concentration of the target SARS-COV-2 and provides a measurement proportional to the viral load of the nanoparticles infecting the human cells. 
     Test unit  210  is one-time use and disposable having been contaminated with biofluid  202  from human subject  200 . Tester  220  is reusable and contains electrical circuitry necessary to measure an ionic current.  FIG. 7  illustrates components of test unit  210  and tester  220 . In tester  220 , test button  222  closes current path  226  to ground terminal  224 . Current path  226  through biosensor  172  passes through conductive layer  164 , core  140 , antibody reagent solution, CSOI backside contact  150 , TSVs  158   a - 158   b , conductive layers  160  and  162  of biosensor  172 . Current path  226  continues through connector  212  and receptacle  218  to the inverting input of low noise amplifier  230 . The non-inverting input of amplifier  230  receives a reference voltage V REF . Resistor  232  is connected between the output of amplifier  230  and its inverting input to set the gain of the amplifier. The output of amplifier  230  is routed through analog-to-digital converter  234  to test processor  236  to analyze the measurements, see  FIG. 6 . Test processor  236  transmits the test signal to test receiver  240  by wireless transmission, e.g., Bluetooth or WiFi, or by direct electrical connection. In one embodiment, test receiver  240  is a smart phone with display  242  to show test results. 
     Upon depositing the biofluid into opening  208  of test unit  210 , inserting connector  212  into receptacle  218 , and pressing activate test button  222 , tester  220  completes current path  226  and allows current to flow in the direction of arrow  238 . If the biofluid contains no SARS-COV-2, the impedance in current path  226  remains at its nominal value and the ionic current flowing through current path  226  remains at its nominal value. If the biofluid contains SARS-COV-2, the antibodies combine with the SARS-COV-2 particles changing the impedance of solution in proximity of the alumina  136  electrode. The change in impedance of the alumina electrode causes a change in the ionic current accompanying the chemical reaction that takes place when the antibodies combine with the SARS-COV-2 particles. The impedance in current path  226 , particularly through the alumina  136  electrode on surface  138  and in core  140 , increases from its nominal value and the ionic current flowing through current path  226  decreases from its nominal value. The decrease in the ionic current is proportional to the amount or concentration of the SARS-COV-2 particles in the test. Accordingly, biosensor detect the presence and concentration of the SARS-COV-2. Test unit  210  with biosensor  172  simplifies and reduces the antibody-antigen reaction test to less than 30 seconds, making the test practical for mass testing at mass screening, such as schools, workplaces, universities, and entertainment and sports venues. Again, other pathogens can be detected by matching with the appropriate reactant antibody solution. 
     In summary, infectious diseases have been a leading cause of mortality worldwide, with viruses making global impact on healthcare and socioeconomic development. The rapid development of drug resistance to currently available therapies and adverse side effects due to prolonged use is a serious public health concern. The interaction of nanostructures with microorganisms is revolutionizing the biomedical field by offering advantages in both diagnostic and therapeutic applications and the necessary diagnostic testing of these illnesses. Test unit  210  with biosensor  172  is highly manufacturable, reliable, and offers a rapid, low cost test capability. Test unit  210  in combination with tester  220  provide a handheld diagnostic unit that is easy to use, through a portable reader and disposable cartridges, with no lab, amplification, or sample prep needed. Mass screening reduces the spread of viruses, particularly during a pandemic. 
     Semiconductor technology, such as DRIE, DWB, and ALD, can contribute to transforming the way infectious diseases are detected, diagnosed, and surveilled by enabling a new era of biosensor point-of-care diagnostics sensors. SOI MEMS can be applied to nanopore biosensors for detection of human infectious disease diagnostics, pathogen surveillance by applying SOI MEMS to detect specific pathogens in samples of nasal fluid, blood, saliva, or other biofluids. 
     While one or more embodiments of the present invention have been illustrated in detail, the skilled artisan will appreciate that modifications and adaptations to those embodiments may be made without departing from the scope of the present invention as set forth in the following claims.