[M-IS08] アストロバイオロジー

[MIS08-09] Label-free single-molecule detection of molecules of astrobiological and astrochemical interest using nanogap-based tunneling current measurements

*高萩 航¹、増田 直旺¹、寺澤 昌平²、柳瀬 航太¹、安部 稜士²、ギンター テーレン²、瀬谷 巧²、大城 敬人³、谷口 正輝³、ロンゴ リアム^1,4、藤島 皓介^1,5 (1.東京科学大学地球生命研究所、2.東京科学大学生命理工学院、3.大阪大学産業科学研究所、4.ブルーマーブル宇宙科学研究所、5.慶應義塾大学大学院政策・メディア研究科)

キーワード：ラベルフリー1分子計測、量子トンネル電流、ナノギャップ、アストロバイオロジー、アストロケミストリー

Single-molecule detection and analysis of complex organic molecules is crucial in fields such as analytical chemistry, molecular biology, and proteomics, where detailed understanding of individual molecular behaviors and interactions underpins both research and diagnostic advancements. Here, we present a nanogap platform for label-free detection of small organic molecules – including non-canonical amino acids and their peptides – based on electron tunneling currents. When molecules transiently occupy the nanogap, their organic conductivity modulate the quantum tunneling current, thus generating characteristic "fingerprints". This approach allows for direct identification of organic molecules without the need for labeling or modifying, and it reveals subtle molecular differences through event statistics, suggesting the feasibility of extracting sequence information with further optimization. Using this platform, we performed nanogap measurements for 20 canonical and 14 non-canonical amino acids, demonstrating clear signal differences among all species tested. To further elucidate the underlying physicochemical parameters, we performed quantum chemical calculations to estimate the HOMO/LUMO energy levels of 34 amino acids in various ionic and neutral forms (cation, anion, zwitterion, and neutral). These computational insights, combined with our nanogap measurements, pave the way towards label-free sequencing technologies for molecules of astrobiological and astrochemical relevance, including RNA, DNA, and peptides. Advanced statistical clustering and pattern recognition algorithms facilitated effective event classification, molecular species discrimination, and ongoing improvements – such as machine learning-based signal processing and optimized electrode functionalization – are expected to further enhance sensitivity, specificity, and throughput.
The small measurement volume, the label-free analytical procedure, and the fact that the measurement system, including tip and instrument, contains no bio-reagents, allowing for long-term storage, are practical advantages for the use of nanogap devices in space exploration. Given its suitability for molecules of astrobiological and astrochemical interest (e.g., RNA, DNA, amino acids, peptides), the method holds promise for detecting potential biosignatures on Mars, life in deep subsurface environments, or evidence of life on the icy moons – thereby extending its relevance to astrobiological investigations.