Is it possible to place a measuring instrument inside a cell? The “organic microlaser” (*1) developed by Associate Professor Yamagishi allows molecular concentrations within cells to be measured at the nanoscale. This new approach combines biocompatibility with high measurement accuracy, which has not been achievable with conventional molecular probes.
Measuring Intracellular Molecules with Organic Microlasers
I am proposing and developing a “laser bioprobe” that is capable of measuring chemical reactions occurring within the complex structure of a cell. A cell may be regarded as a “container enclosing countless molecules and proteins”. My goal is to create a probe with the ability to measure the dynamically changing concentrations of molecules inside a cell in real time.
Using a technique called “molecular assembly”, which forms spherical particles by isotropically gathering molecules, I aggregated organic dye molecules and organic polymers. This allowed me to fabricate microlasers as intended from materials that possess probe functions, and the results obtained were published in 2021. Furthermore, by examining molecular concentration sensors based on these devices, we successfully detected trace gas molecules at concentrations <1 ppm.
In the next stage, we are attempting to introduce the laser into living cells in order to measure molecular concentrations (right figure). In the future, host molecules or antibodies will be attached to the surface of the microlaser, thereby allowing it to identify and measure specific molecules. The quantitative detection of subtle or transient changes in the expression levels of particular molecules or proteins will be possible. Researchers in the biological sciences have suggested several applications, such as measuring ATP (*2) expression changes in response to a mechanical stimulation, monitoring changes in heat shock factor expression induced by temperature variations, and quantifying odor molecules locally. We plan to work on these topics.
(Figure) In the case of organic fluorescent molecules (left), the emission band has a broad wavelength width, ranging from several tens to several hundred nanometers, causing emissions from dyes with similar colors to overlap. In contrast, organic microlaser light (right) exhibits an extremely sharp emission peak with a width of approximately 0.1 nm. (Illustration by YAMAGISHI Hiroshi)
The Challenge of Achieving High-precision Measurements
I selected this organic approach to address the limitations of conventional measurement methods. One established approach for assessing protein concentrations is colorimetric measurements, which detect relative changes in fluorescence spectra using organic fluorescent molecules. In this method, fluorescent molecules are introduced into a cell, and the wavelength shift in the excitation light caused by reactions with proteins is measured. However, the accuracy of conventional fluorescent probes is around the micromolar level, which falls short of the nanomolar precision that is often required (left figure).
In recent years, researchers have investigated the use of microlasers as a new type of optical probe to replace fluorescent probes; however, practical implementation has yet to be achieved. The majority of microlasers currently in use are made from inorganic materials, such as gallium arsenide, which are unsuitable for long-term measurements due to their toxicity. Moreover, because these materials are inorganic, it is difficult to attach molecular recognition sites, such as antibodies or host molecules, to their surfaces. In contrast, organic materials are expected to overcome these challenges because they exhibit higher affinity with intracellular molecules.
Examining Life Phenomena from the Perspective of Organic Chemistry
As an organic chemist, I enjoy advancing my research while considering which molecules to use in order to build microlasers and also which optical properties to harness. Cells are extremely complex machines, and my strongest motivation is to capture their behavior in real time. Drawing on the results of this study, I also hope to take on the challenge of constructing novel biological systems.
(*1) Microlaser: A laser light source measuring only a few micrometers in size, studied in the field of photophysics.
(*2) ATP: Abbreviation for adenosine triphosphate. The energy released during its conversion to adenosine diphosphate serves as an essential energy source for vital biological processes.
(Date of interview: August 19, 2025)
