A droplet-based system enables high-throughput single-cell RNA sequencing (scRNA-seq) for analyzing the transcriptomes of tens of thousands of individual cells. The system uses microfluidics to encapsulate cells in droplets, allowing for efficient processing and sequencing. It achieves a 50% cell capture rate and can process up to eight samples per run. The system uses barcoded oligonucleotides to index cells and enables the detection of rare populations. It was validated using cell lines and synthetic RNAs, demonstrating its sensitivity and ability to detect low-frequency cell populations. The system was used to profile 68,000 peripheral blood mononuclear cells (PBMCs), revealing distinct immune subpopulations. It also enabled the detection of donor and host chimerism in bone marrow samples from transplant patients by analyzing single nucleotide variants (SNVs). The system's ability to detect rare cell populations and its high throughput make it a valuable tool for studying complex biological systems. The technology was applied to analyze PBMCs from healthy donors and transplant patients, revealing subpopulation differences and providing insights into disease states. The system's scalability and high-throughput nature allow for the analysis of large numbers of cells, making it suitable for various applications in biomedical research. The study highlights the potential of this technology for improving clinical outcomes by enabling detailed analysis of cellular composition and disease progression.A droplet-based system enables high-throughput single-cell RNA sequencing (scRNA-seq) for analyzing the transcriptomes of tens of thousands of individual cells. The system uses microfluidics to encapsulate cells in droplets, allowing for efficient processing and sequencing. It achieves a 50% cell capture rate and can process up to eight samples per run. The system uses barcoded oligonucleotides to index cells and enables the detection of rare populations. It was validated using cell lines and synthetic RNAs, demonstrating its sensitivity and ability to detect low-frequency cell populations. The system was used to profile 68,000 peripheral blood mononuclear cells (PBMCs), revealing distinct immune subpopulations. It also enabled the detection of donor and host chimerism in bone marrow samples from transplant patients by analyzing single nucleotide variants (SNVs). The system's ability to detect rare cell populations and its high throughput make it a valuable tool for studying complex biological systems. The technology was applied to analyze PBMCs from healthy donors and transplant patients, revealing subpopulation differences and providing insights into disease states. The system's scalability and high-throughput nature allow for the analysis of large numbers of cells, making it suitable for various applications in biomedical research. The study highlights the potential of this technology for improving clinical outcomes by enabling detailed analysis of cellular composition and disease progression.