# High-Throughput DNA Analysis Platform Based on an Optofluidic Ring Resonator Laser
## 1 Introduction  
A DNA sequence holds the most fundamental information about an individual life form; thus, its analysis offers significant potential for a variety of studies related to biology and medicine [1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14]. Traditional DNA sequence analysis, such as high-resolution melting (HRM) [3; 15], is widely used not only in lab-scale research but also in real-world applications for pathogen diagnostics. During the recent coronavirus disease of 2019 (COVID-19) pandemic, real-time polymerase chain reaction (PCR), which is based on HRM, has been utilized as the standard diagnostic tool since it is the most powerful and reliable technique available.  
However, laser-based DNA analysis schemes have been introduced in the last few years, challenging the traditional PCR technique in simplicity, sample consumption, and particularly in detection speed [16; 17; 18; 19; 20; 21; 22]. Since a laser is a nonlinear optical phenomenon with a laser threshold, DNA sequences can be analyzed with a single laser emission. When compared with traditional DNA analysis, which takes at least a few hours, laser-based analysis has a huge advantage in rapid, high-throughput DNA sequential detection.  
DNA detecting lasers that have been described mostly utilize optofluidic platforms, and laser gain has been obtained using dyes labeled with DNA or intercalating dyes. Similarly to traditional fluorescence-based analyses, dye-labeled DNA molecules, such as molecular beacons, have allowed for efficient DNA detecting lasers; however, they include complex DNA labeling sample preparation processes [16; 18; 20]. The use of intercalating dyes rendered laser-based DNA analysis simple and cost-effective, and lasers were obtained with several different laser cavities/schemes [17; 21]. While an optofluidic platform with a Fabry-Perot cavity implemented laser-based DNA detection [22], a few different ring resonator cavities exhibited superior laser characteristics owing to an intrinsically higher Q factor. The very first form of the optofluidic ring resonator (OFRR)-based DNA laser was introduced in 2012 [17]. This technique utilizes a glass capillary filled with a DNA sample mixed with intercalating dye, demonstrating that DNA sequences can be simply and rapidly detected using DNA laser emission. However, since the non-target DNA stillemits fluorescence, which does not contribute to the laser feedback, the analysis cannot be regarded as a \"digital-like\" scheme from an optical standpoint. DNA probe molecules functionalized on the surface of the OFRR enabled a truly digital-like optical detection of DNA sequences, suppressing the fluorescence background from the non-target DNA molecules [21]. A drawback of this novel method is that pretreatment of the OFRR with a DNA probe hinders the performance of a rapid, high-throughput DNA analysis platform, which is the most desirable trait of laser-based DNA analysis to replace existing traditional DNA analysis.  
In this study, we propose an OFRR laser scheme using microdroplets of a DNA/ intercalating dye and investigate optically true, digital-like DNA sequence detection to yield a realistic, rapid, high-throughput DNA analysis platform. The nL-sized microdroplets filled with a simple mixture of DNA and intercalating dye are individual reaction chambers for high-throughput analysis, and the glass-capillary-based OFRR laser connected downstream detects the DNA laser by analyzing their sequences. The laser emission was subsequently detected by the fiber taper to reject the unwanted fluorescence background. This resulted in a truly digital optical signal similar to the DNA laser with the surface-functionalized OFRR.