| Reliable and quantitative detection of ultra-low concentrations of biomarkers is of great importance in clinical applications.The current traditional clinical diagnostic methods,such as turbidimetric methods,microscopic analysis and cell culture,are both time-consuming and expensive,and are also not suitable for on-site diagnosis.Therefore,there is an urgent need for a sensitive,specific and rapid detection device for biomarker analysis.Silicon nanowire(SiNW)biosensors have become an important representative of the new generation of biosensors due to their high specificity,fast response time,and good biocompatibility.However,there is still a limitation of low sensitivity in the actual low concentration biomarker detection,which limits its application in clinical testing.In this paper,a SiNW biosensor was prepared based on the sidewall transfer technology in integrated circuit process,and its detection sensitivity was improved by design and process optimization,and the ultra-low concentration detection of cystatin C(CysC),a marker of kidney disease,was achieved by using its high sensitivity in the subthreshold region.The main research contents and results of this paper are as follows:1.The factors affecting the sensitivity of SiNW biosensors were studied and analyzed using the field-effect transistor biosensor signal variation tool(BioFET-SIM)model.The design and process optimization of high-sensitivity biosensors were carried out by combining domestic and international methods to improve the sensitivity of SiNW sensors.On the one hand,the effect of doping concentration on the working state of SiNW was investigated by regulating the doping concentration to achieve high-sensitivity detection.The experimental results show that the SiNW biosensor injected with a dose of 1E13 atoms/cm~2 can achieve highly sensitive sensing detection in the subthreshold region.On the other hand,the contact between its source-drain region and Al electrode is optimized by surface treatment of nickel-platinum metal silicide(NiPt-Silicide)and source-drain electrode,which effectively reduces the parasitic resistance of the device and improves the stability of the sensor for high-sensitivity detection.2.In order to improve the modification density of probe molecules on the SiNW surface,a polydimethylsiloxane(PDMS)microfluidic channel was designed and prepared.It was bonded to the surface of the sensing region of the SiNW biosensor by oxygen plasma treatment to pass the probe molecule and the target molecule to the SiNW surface accurately and efficiently,thus improving the modification density of the probe molecule and the binding probability of the target molecule,and being able to reduce the interference of the external environment.The experimental results show that the addition of PDMS microfluidic channels effectively improves the stability of detection and the sensitivity of sensing.3.The quantitative detection of CysC,a marker of nephropathy,was carried out using the prepared high-sensitivity SiNW biosensor.The results showed that the sensor could achieve the sensing response to ultra-low concentration of CysC solution with a linear detection range of 1 ag/mL to 1 ng/mL,and the fitted detection limit was0.253 ag/mL.The SiNW biosensor has the advantages of high sensitivity,high specificity and fast detection speed compared with other detection methods,and is compatible with the complementary metal oxide semiconductor(CMOS)process for large-scale and low-cost preparation.The SiNW biosensor is compatible with complementary metal-oxide-semiconductor(CMOS)processes and can be prepared on a large scale at low cost.The SiNW biosensor designed and prepared in this paper provides a portable and reliable detection platform for the clinical detection of biomarkers. |
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