Biosensors can detect biomolecular interactions, thus have important applications in many areas including biomedicine, food safety, biosafety, environment protection.
We are doing research on label-free optical biosensors based on a CMOS compatible nanomaterial-porous silicon. Porous silicon is a nanostructured material with high surface area and tunable morphology, making it very suitable for constructing biosensors [APL2008, Biosensors and Bioelectronics]. In addition, we exploit Localized Surface Plasmon Resonance (LSPR) with resonant optical porous silicon devices to achieve high sensitivity of biomolecular detection (see Figure 1).
The optical biosensors based on porous silicon can be measured by portable fiber spectrometer [Physica E]. The optical measurement can also be completed by robots (see Video 1). Together with automatic specimen loading and biosensor surface rinsing (see Video 2), the automatic operation can help professionals to avoid biohazards. For the recent COVID epidemic, we have developed a rapid, on-site, fully automatic SARS-CoV-2 detection system (see Figure 2). When combined with porous silicon optical biosensor, the system can provide powerful population-scale screening. Both the biosensor and the detection system are of low cost and readily scalable to accommodate different population size. Furthermore, the biosensor, together with a handheld reflection spectroscopy system, can be utilized for personal or home use for health monitoring. Moreover, we are utilizing the biosensor and measurement system for detecting many other kinds of pathogens in environment, such as air, water and surface of the objects [NANO2012]. Our system has been deployed in Zhejiang and Hangzhou Centers for Disease Control and Prevention (CDC) for research use. Some data is shown in Figure 3. In collaboration with Hangzhou CDC, we are also developing a mobile P2 lab inside a modified van to carry out rapid and onsite detection of pathogens in high-risk environment.
Related Publications: APL2008, Biosensors and Bioelectronics, Physica E, NANO2012, IEEE EMBC 2020
Figure 1. Fabrication of porous silicon: (a) Six-inch diameter wafer where the active area is 11 cm in diameter, (b) PDMS well-based array on wafer in 96-well format from which a PDMS 6×7 well array is cut to form a biosensor chip. The enlarged view of a single well shows that within each well, a 2×2 spot array is defined through a robotic arm control program with each 0.5-mm diameter spot measured by reflection spectroscopy, (c) Binding of SARS-CoV-2 by engineered trimeric angiotensin converting enzyme-2 (T-ACE2) immobilized on biosensor surface.
Figure 2. The proposed sensing platform consisting of biosensor array chip, fiber spectrometer, Y-shaped fiber, 8 or 12 headed pipette, two-robotic arms used for alignment/measurement, and sample loading/rinsing. Note that the halogen white light source is not shown in this figure.
Figure 3. (a) shows the response of the biosensor for detection of S-ECD protein (40 nM). The biosensor has a specific response for S-ECD viral protein and a negligible response for PBS buffer only. For both samples, a total of three wells with one spot in each well were measured, and three measurements were taken both before and after the sample reaction with T-ACE2. (b) shows the response of the biosensor as a function of pseudovirus concentration. The biosensor response increases with increasing pseudovirus concentration, and the limit of detection is more than 107 copies/ml. For all specimens, a total of three wells with one spot in each well were measured, and three measurements were taken both before and after the sample reaction with T-ACE2. (c) shows the red shift of the biosensor as a function of inactivated SARS-CoV-2 virus concentration. Four spots (2×2 array) within each well were measured for each concentration, and three measurements were completed for each spot both before and after virus binding. The height of the red shifts increases as virus concentration increases. The response for negative controls is also shown including the culture medium and five clinical throat swab specimens of patients infected by viruses other than SARS-CoV-2 as diagnosed by RT-PCR: human bocavirus, enterovirus, adenovirus, parainfluenza virus Type 3 (PIV-3), and influenza A. The limit of detection is estimated to be 100 TCID50/ml, which is better than the state-of-the-art antigen detection methods with limits of detection of several hundred to thousands of TCID50/ml
Video 1. Robotic operation of experiment
Video 2. Automatic specimen loading and biosensor surface rinsing