Sa Cai

All Publications

• A frugal CRISPR kit for equitable and accessible education in gene editing and synthetic biology. Nature communications Collins, M., Lau, M. B., Ma, W., Shen, A., Wang, B., Cai, S., La Russa, M., Jewett, M. C., Qi, L. S. 2024; 15 (1): 6563

  Abstract

  Equitable and accessible education in life sciences, bioengineering, and synthetic biology is crucial for training the next generation of scientists, fostering transparency in public decision-making, and ensuring biotechnology can benefit a wide-ranging population. As a groundbreaking technology for genome engineering, CRISPR has transformed research and therapeutics. However, hands-on exposure to this technology in educational settings remains limited due to the extensive resources required for CRISPR experiments. Here, we develop CRISPRkit, an affordable kit designed for gene editing and regulation in high school education. CRISPRkit eliminates the need for specialized equipment, prioritizes biosafety, and utilizes cost-effective reagents. By integrating CRISPRi gene regulation, colorful chromoproteins, cell-free transcription-translation systems, smartphone-based quantification, and an in-house automated algorithm (CRISPectra), our kit offers an inexpensive (~$2) and user-friendly approach to performing and analyzing CRISPR experiments, without the need for a traditional laboratory setup. Experiments conducted by high school students in classroom settings highlight the kit's utility for reliable CRISPRkit experiments. Furthermore, CRISPRkit provides a modular and expandable platform for genome engineering, and we demonstrate its applications for controlling fluorescent proteins and metabolic pathways such as melanin production. We envision CRISPRkit will facilitate biotechnology education for communities of diverse socioeconomic and geographic backgrounds.

  View details for DOI 10.1038/s41467-024-50767-2

  View details for PubMedID 39095367

• Bioinspired nanotransducers for neuromodulation NANO RESEARCH Yang, F., Wu, X., Cai, S., Hong, G. 2023

  View details for DOI 10.1007/s12274-023-6136-6

  View details for Web of Science ID 001076987400003

• Nanotransducer-Enabled Deep-Brain Neuromodulation with NIR-II Light. ACS nano Wu, X., Yang, F., Cai, S., Pu, K., Hong, G. 2023

  Abstract

  The second near-infrared window (NIR-II window), which ranges from 1000 to 1700 nm in wavelength, exhibits distinctive advantages of reduced light scattering and thus deep penetration in biological tissues in comparison to the visible spectrum. The NIR-II window has been widely employed for deep-tissue fluorescence imaging in the past decade. More recently, deep-brain neuromodulation has been demonstrated in the NIR-II window by leveraging nanotransducers that can efficiently convert brain-penetrant NIR-II light into heat. In this Perspective, we discuss the principles and potential applications of this NIR-II deep-brain neuromodulation technique, together with its advantages and limitations compared with other existing optical methods for deep-brain neuromodulation. We also point out a few future directions where the advances in materials science and bioengineering can expand the capability and utility of NIR-II neuromodulation methods.

  View details for DOI 10.1021/acsnano.2c12068

  View details for PubMedID 37079455

• Systemically Delivered, Deep-Tissue Nanoscopic Light Sources PROGRESS IN ELECTROMAGNETICS RESEARCH-PIER Wu, X., Yang, F., Cai, S., Hong, G. 2023; 177: 33-42

  View details for Web of Science ID 000968675700001

• Palette of Rechargeable Mechanoluminescent Fluids Produced by a Biomineral-Inspired Suppressed Dissolution Approach. Journal of the American Chemical Society Yang, F., Wu, X., Cui, H., Jiang, S., Ou, Z., Cai, S., Hong, G. 2022

  Abstract

  Mechanoluminescent materials, which emit light in response to mechanical stimuli, have recently been explored as promising candidates for photonic skins, remote optogenetics, and stress sensing. All mechanoluminescent materials reported thus far are bulk solids with micron-sized grains, and their light emission is only produced when fractured or deformed in bulk form. In contrast, mechanoluminescence has never been observed in liquids and colloidal solutions, thus limiting its biological application in living organisms. Here, we report the synthesis of mechanoluminescent fluids via a suppressed dissolution approach. We demonstrate that this approach yields stable colloidal solutions comprising mechanoluminescent nanocrystals with bright emissions in the range of 470-610 nm and diameters down to 20 nm. These colloidal solutions can be recharged and discharged repeatedly under photoexcitation and hydrodynamically focused ultrasound, respectively, thus yielding rechargeable mechanoluminescent fluids that can store photon energy in a reversible manner. This rechargeable fluid can facilitate a systemically delivered light source gated by tissue-penetrant ultrasound for biological applications that require light in the tissue, such as optogenetic stimulation in the brain.

  View details for DOI 10.1021/jacs.2c06724

  View details for PubMedID 36190898

• A biomineral-inspired approach of synthesizing colloidal persistent phosphors as a multicolor, intravital light source. Science advances Yang, F., Wu, X., Cui, H., Ou, Z., Jiang, S., Cai, S., Zhou, Q., Wong, B. G., Huang, H., Hong, G. 2022; 8 (30): eabo6743

  Abstract

  Many in vivo biological techniques, such as fluorescence imaging, photodynamic therapy, and optogenetics, require light delivery into biological tissues. The limited tissue penetration of visible light discourages the use of external light sources and calls for the development of light sources that can be delivered in vivo. A promising material for internal light delivery is persistent phosphors; however, there is a scarcity of materials with strong persistent luminescence of visible light in a stable colloid to facilitate systemic delivery in vivo. Here, we used a bioinspired demineralization (BID) strategy to synthesize stable colloidal solutions of solid-state phosphors in the range of 470 to 650 nm and diameters down to 20 nm. The exceptional brightness of BID-produced colloids enables their utility as multicolor luminescent tags in vivo with favorable biocompatibility. Because of their stable dispersion in water, BID-produced nanophosphors can be delivered systemically, acting as an intravascular colloidal light source to internally excite genetically encoded fluorescent reporters within the mouse brain.

  View details for DOI 10.1126/sciadv.abo6743

  View details for PubMedID 35905189

• Tether-free photothermal deep-brain stimulation in freely behaving mice via wide-field illumination in the near-infrared-II window. Nature biomedical engineering Wu, X., Jiang, Y., Rommelfanger, N. J., Yang, F., Zhou, Q., Yin, R., Liu, J., Cai, S., Ren, W., Shin, A., Ong, K. S., Pu, K., Hong, G. 2022

  Abstract

  Neural circuitry is typically modulated via invasive brain implants and tethered optical fibres in restrained animals. Here we show that wide-field illumination in the second near-infrared spectral window (NIR-II) enables implant-and-tether-free deep-brain stimulation in freely behaving mice with stereotactically injected macromolecular photothermal transducers activating neurons ectopically expressing the temperature-sensitive transient receptor potential cation channel subfamily V member 1 (TRPV1). The macromolecular transducers, ~40 nm in size and consisting of a semiconducting polymer core and an amphiphilic polymer shell, have a photothermal conversion efficiency of 71% at 1,064 nm, the wavelength at which light attenuation by brain tissue is minimized (within the 400-1,800 nm spectral window). TRPV1-expressing neurons in the hippocampus, motor cortex and ventral tegmental area of mice can be activated with minimal thermal damage on wide-field NIR-II illumination from a light source placed at distances higher than 50 cm above the animal's head and at an incident power density of 10 mW mm-2. Deep-brain stimulation via wide-field NIR-II illumination may open up opportunities for social behavioural studies in small animals.

  View details for DOI 10.1038/s41551-022-00862-w

  View details for PubMedID 35314800