Simultaneous Detection Of Multiple Biological Targets Based On Optical Microcavities

Biological detection is an essential step of disease diagnosis,drug analysis and life science-related research.It plays an important role in clinical diagnosis and treatment,food safety and environmental monitoring.Qualitative or quantitative biological target detection can reflect the situation of the samples quickly and accurately,which is benefical to conduct timely disease diagnosis and quality control.At present,infectious diseases and cardiovascular diseases seriously threaten people’s health.Rapid and sensitive detection of pathogenic bacteria and specific biomarkers is a crucial step in the disease diagnosis.Traditional detection methods possess many disadvantages such as consuming time,low sensitivity and specificity,complex sample pretreatment and so on.In complex biological environments,it is difficult to realize rapid,accurate and ultra-sensitive detection of biological targets.With the advancement of technology,surface-enhanced Raman scattering and optical microcavity technologies have gradually developed showing great potential in sensitive biological detection.In this paper,we combined the above two technologies and constructed ultra-sensitive biosensors to detect common pathogenic bacteria and cardiac markers,which provides technical support for the diagnosis of infectious diseases and cardiovascular diseases.The research mainly includes the following two points:1.Dual-mode composite microcavity biosensors for ultra-sensitive simultaneous detection of two pathogenic bacteriaA PS/Au composite microcavity aptasensor was constructed using gold nanoparticles and polystyrene microspheres.Through the functional microcavity aptasensors,the simultaneous detection of two common pathogenic bacteria,Staphylococcus aureus and Escherichia coli,was realized in a complex biological environment.The composite microcavities were modified with different fluorescent dyes inside and different Raman signal molecules and specific aptamers on the surface.Fluorescent images of the samples were achieved by the signal from fluorescent dyes and visible qualitative analysis and semi-quantitative counting of the samples can be realized through the images.At the same time,Raman spectra were achieved from Raman signal molecules to conduct quantitative detection of S.aureus and E.coli.The Raman signal intensity presented a great linear relationship with the bacteria concentration.The localized surface plasmon resonance phenomenon of gold nanoparticles and the light-limiting effect of polystyrene microcavity synergetically enhanced the scattering signal of Raman molecules.The Raman enhancement factor reached 2.25×10¹¹ and the detection limits（LOD）of S.aureus and E.coli reached 3cfu/m L and 2 cfu/m L,respectively.2.Plasmon-coupled WGM microsphere cavity for ultra-sensitive simultaneous detection of two cardiac markersZnO microspheres were prepared by hydrothermal method and gold nanoparticles were modified on their surface by ion sputtering to construct a kind of ZnO/Au composite microcavity SERS substrate.Through the substrate,the ultra-sensitive detection of c Tn I and CK-MB were realized in serum.The high refractive index of ZnO makes it become a good optical confinement material.The combination of the surface plasmons of the gold nanoparticles and the WGM effect of ZnO microcavity made the composite microcavity possess a strong ability to enhance optical signal.Additionally,there also existed chemistry enhancement resulted from electron transfer.The Raman enhancement factor reached 1.14×10¹¹ and the LOD of c Tn I and CK-MB reached 7.7 pg/m L and 3.2 pg/m L,respectively.Meanwhile,the quantitative detection of c Tn I and CK-MB was successfully achieved in the range from 0.01 ng/m L to 100 ng/m L.