Printed on a Chip, Living Laser Is an Adept Biosensor

A standard inkjet printer is at the heart of a new method that Nanyang Technological University Singapore and China (NTU Singapore and China) developed for monitoring the sometimes subtle interactions between bacteria and antibiotics. The researchers’ approach produced a disposable “living laser on a chip” that supports direct drug-screening applications.

The technology, they said, could enable increasingly sensitive and high-throughput testing using micronano laser technology.

Introduced in a study led by NTU Singapore’s Yu-Cheng Chen, the living laser incorporates multiple microlasers printed from an office-quality inkjet printer, functioning as a highly sensitive and culture-free sensor and capable of being fabricated into a mass dimension in seconds. The sensor serves to encapsulate living bacteria in micro-size water droplets. The system is also washable in addition to being disposable.

Its value lies in the need to improve on conventional techniques that take longer periods of time to indicate even obvious drug interactions involving bacteria and antibiotics, and may not be optimally sensitive.

The researchers built the sensor in a three-step process that began with labeling bacteria with nuclei acid dyes capable of recognizing DNA and RNA present in cells. Team members then injected the cells and cell media into an office printer into which antibiotic drugs could then be added directly into the printhead. Hemisphere microdroplets were then printed in array patterns on mirror chips.

A laser beam scanned the “living” laser arrays, generating emission images from whispering-gallery modes (WGMs). Those WGMs were themselves enhanced, resulting in a stronger laser emission, by the result of the drug’s interaction with the bacteria. In that process, the cell membrane was destroyed, releasing more fluorescent DNA, or gain molecule, into the droplet over time.

Because the laser signal is sensitive to the changes of the dye molecules at the droplet interface, the intact system was able to capture minute increases of the released DNA, resulting in a significant change in the laser emissions and gain distribution. Testing ultimately showed that laser emission image analysis was more sensitive than fluorescence image analysis by two orders of magnitude — also considering that fluorescence images saturate over time.

“Our findings show that the amplification that occurs during laser generation enabled us to quantify tiny changes in biological processes in the gain medium,” Chen said.

According to NTU’s Shilun Feng, co-author of the study describing the biosensor, the same approach that the team employed to merge microfluidic fabrication with on-chip lasing could be applied to arrange living species with high sensitivity.

“With the rapid needs for drug screening against viruses, this technology could even enable viruses or bacteria to culture inside the microdroplets and monitor the dynamic interactions with drugs,” Feng said.

The research was published in Analytical Chemistry (www.doi.org/10.1021/acs.analchem.1c00020).