Floating-Gate Carbon Nanotube FET Biosensor For Detection Of Disease

In today’s medical diagnosis,the detection of disease biomarkers with ultra-low concentration is very important.At present,Polymerization chain reaction（PCR）technology and Enzyme-Linked Immuno Sorbent Assay（ELISA）test paper are commonly used to detect gene screening and cancer diagnosis respectively in China.However,some of these methods need to require the labeling of target biomolecules and involve complicated equipment,impeding their application in Point-of-Care Test（POCT）devices.Therefore,it is urgent to develop a biosensing platform with miniaturization,high-throughput,ultrasensitive,and cost effective.In recent years,due to the excellent electrical properties and ultra-high specific surface area of nanomaterials and the continuous development of semiconductor device manufacturing technology,Field Effect Transistor（FET）biosensors constructed with nanomaterials have been widely concerned.In the past ten years,many FET biosensors with nano-materials have been reported continuously,but these biosensors have some problems,such as being unable to be mass-produced and prepared,not stable enough,poor uniformity and low sensitivity,So there is still no relevant product on the biosensor market.Semiconductor carbon nanotubes（CNTs）are considered as ideal channel materials for building ultra-sensitive field effect transistor biosensors because of their atomic-thickness bodies,excellent electrical properties,good biocompatibility and good size compatibility.But the fabrication of reproductive,stable,and ultrasensitive CNT FET-based biosensors on a large scale is still challenging.Furthermore,because the structure of the traditional CNT FET biosensor is not optimized,which makes the performance of the sensor cannot be further improved.thus greatly reducing the development potential of the carbon nanotube FET biosensor in practical application.In this paper,firstly,we use solution method to produce high-purity carbon nanotube materials on a large scale,through combining device structure optimization,and material advancement to overcome previous limitations.We fabricated CNT FETs with high uniformity on a 4-inch substrate based on photolithography.The fabricated CNT FETs devices were characterized,and demonstrated good performance,such as,The overall distribution of the subthreshold swing（SS）is 80 m V/dec,the current on/off ratios as high as 10⁵～10⁶,Bias stress measurements indicate that the device presents long-term stability for sensing applications.Secondly,Because the channel material of the traditional FET biosensor is directly exposed to the external environment,the different influences of the external environment and functional materials on the channel make the sensing mechanism of the sensor complex,and it is difficult to achieve uniform performance and high sensitivity of the sensor.To solve these problems,we propose the structure of a biosensor based on the floating gate type FET,the introduction of dielectric layer isolates the influence of external environment and functional materials on the electrical properties of carbon nanotubes to a certain extent,so that the sensor shows better uniformity and stability,and this structure is compatible with the fabrication process of carbon-based integrated circuit,so it can be an ideal structure for the construction of carbon-based biosensor platform.In this paper,we continue to optimize the process to prepare a kind of Y₂O₃ thin film,which is used as gate dielectric,and have realized the fabrication of high-quality floating gate carbon nanotube field effect transistor.Then,the biological probe molecules were immobilized on the surface of the device.Finally,we analyze the working mechanism of floating gate FET sensor and traditional FET sensor.Through experimental and theoretical analysis,floating gate FET sensor can maintain good uniformity and stability in low concentration environment and high concentration environment,and has high sensitivity.As demonstrations,FG CNT FETs are used to construct biosensors for detecting specific DNA sequences for Patau syndrome screening and microvesicles（MVs）secreted by hepatoma carcinoma cells.After analyzing the static test results,the theoretical record detection limits as low as 100 a M and 6 particles/μL.respectively,with excellent specificity and stability.On this basis,we tested the sensor in real time,and the test results are consistent with the static test results.The sensor can respond quickly to DNA molecules with a concentration of 100 a M.And the sensor still has good stability under bias stress.The floating gate CNTs FET biosensor proposed in this work can be developed into a universal biosensing platform.By changing the connecting molecules of different biological probes,the selective detection of different disease markers can be realized.The recent advances of CNT-based integrated circuits together with the biosensor platform we developed show that,the CNT FET-based sensor architectures is expected to be combined with carbon-based integrated circuits to realize highly integrated and multiplexed carbon-based intelligent biosensor chips,which has great application potential in future medical diagnostics and other fields.