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Engineers Develop Photonic Chipscope Enabling Label-Free Monitoring of Live Cell Activities

Understanding numerous biological processes and the response of cells to therapeutic drugs requires label-free, non-invasive, and statistical monitoring of cellular activity.

Engineers Develop Photonic Chipscope Enabling Label-Free Monitoring of Live Cell Activities.
Dr. Yuan Lin (left) and Dr. Zhiqin Chu (right). Image Credit: The University of Hong Kong

Existing techniques, on the other hand, are sometimes hampered by several time-consuming preparation procedures, complex apparatus, and incompatibility, all of which might interact with cells and generate undesirable effects.

In collaboration with Dr. Kwai Hei Li of the Southern University of Science and Technology, an interdisciplinary research team headed by Dr. Zhiqin Chu of the Department of Electrical and Electronic Engineering at the University of Hong Kong (HKU) and Dr. Yuan Lin of the Department of Mechanical Engineering at HKU has developed a low-cost, highly miniaturized, and incubator compatible GaN chipscope.

The GaN chipscope enables the real-time tracking of cells in the constricted and humid space of an incubator.

This viable device would contribute to the creation of a new class of biosensors while also providing fresh insights into fundamental cell biology and drug discovery research. The team has applied for a provisional patent in the United States.

Label-free analysis, as opposed to traditional fluorescent molecules and radionuclide-based labeling approaches, allows for real-time monitoring of bio signals without the need for artificial sample modification.

It preserves the intrinsic states of the targeted samples, reducing negative effects on the native conformation and biological activity of the ligands, cells, or tissues.

Electric impedance sensing-based microelectronic sensors are now the most popular label-free sensing technology on the market. This electric sensor has a well plate with an array of gold biosensors that allows real-time impedance detection to track and measure live cell adhesion dynamics.

However, samples sensitive to electrical signals, like nerves and myocardium, might be harmed by the electric field used there.

Due to their non-invasive and label-free nature, optical evanescence field-based sensing techniques, such as resonant waveguide grating biosensor (RWG) and surface plasmon resonance (SPR), have received a lot of attention in recent years.

Although these technologies have excellent optical precision and have been extensively used in the research of biomolecule interactions and the detection of living cell activities, they have a high demand for the testing condition and general set-up, posing significant limitations to their wide application in a variety of environments.

The well-known GaN-based monolithic chipscope now includes a customized small differential interference contrast (DIC) microscope that can statistically track the course of several intracellular processes without the use of labels.

It allows for real-time imaging of cellular/subcellular ultrastructural characteristics in the incubator as well as a photoelectric readout of cellular/subcellular refractive index (RI) changes.

A microscale InGaN/GaN-based light emission and photodetection subunits (LED-PD) are integrated into a miniaturized GaN photonic chip at the core of this device. Its distributed Bragg reflector’s unique layered construction may substantially improve light-gathering efficiency.

The photoelectric detection capability of the miniaturized GaN photonic chip enables real-time refractive index monitoring generated by collective cell behaviors at the chip surface. Meanwhile, users can precisely catch cell morphology changes in real-time thanks to the integrated mini-DIC imaging technology.

The platform can quantitatively recognize cell activities in situ, such as cell precipitation, initial attachment, spreading, shrinkage, and so on, by combining the imaging unit with the RI sensing unit. This simple, ready-to-use cell analyzer has been used to successfully assess pharmacological activity and track immune cell subtypes.

This study broadens the scope of GaN photonic chip applications in biosensing. The combined strategy of chip sensor and optical imaging, in particular, goes above the limitations of traditional “photonic chip” and “microscopy” monitoring methods. The resultant “chipscope” is a huge and exciting step forward in biosensor development.

Journal Reference:

Hou, Y., et al. (2022) A Versatile, Incubator-Compatible, Monolithic GaN Photonic Chipscope for Label-Free Monitoring of Live Cell Activities. Advanced Science. doi:10.1002/advs.202200910.

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