Cell sorting allows researchers to isolate rare cell types from a heterogeneous population, increasing the number of cells available for downstream analysis. There are five “pillars” of cell sorting used as key performance criteria for a successful sort: viability, recovery, efficiency, purity and proliferation.

The main advantage of conventional cell sorters is that they are generally high-throughput, making them ideal for applications that require large numbers of cells. However, this comes with a drawback: due to the high pressure, electric charge, and shear forces involved, as well as the lack of temperature control throughout the process.

Gentle cell sorting is crucial because it preserves cell viability, functionality and physiological state. High-pressure sorting can cause stress-induced transcriptional changes, skewing results in gene expression analysis. Gentle sorting minimizes this stress, providing a more accurate picture of the cell's true state. For research in fields like oncology and regenerative medicine, it's crucial that downstream results reflect the true biology of the cells, not artifacts of the sorting process. In today’s cell research, this is especially vital as cell sorters must work with increasingly diverse cells—from fully functional innate immune cells to antigen-specific T cells, induced pluripotent stem cells, stem cells, organoids, neurons and more.

Technologies designed to improve on conventional sorting incorporate a range of features for gentler, safer, more consistent sorting of cellular populations.

More lasers

The MACSQuant Tyto Lux Cell Sorter from Miltenyi Biotec has integrated, patented microchip-based technology that provides gentle sorting for a myriad of applications, including fruit dye-expressing cells, rare or fragile cell populations, hazardous or infectious samples, cell line development, reporter protein research and more.

Equipped with an additional yellow laser and up to 12 fluorescent channels, the MACSQuant Tyto Lux Cell Sorter enhances flexibility in panel design. The closed, disposable cartridge provides a sterile, aerosol-free environment that protects both sample and operator—even when handling high-risk samples.

Hands-free operation, intuitive software, and optimized performance allow for a precise and efficient cell sorting workflow. The pre-installed MACSQuantify Tyto Software 3.2 provides optimized sort modes, high-speed performance, and seamless integration into GMP workflows with an optional GMP-ready 21 CFR Part 11 software module.

Personalized medicine case study

Ali Mohamed, Vice President of CMC Immatics—a clinical stage biopharmaceutical company focusing on T cell cancer immunotherapies in Houston—is using the MACSQuant Tyto in his current ACTolog multi-target pilot study. ACTolog is an adoptive cell therapy (ACT) using a patient’s own T-cells.

For the study, tumor antigen expression is tested from fresh tumor biopsies before the personalized cell therapy is produced. During this biomarker profiling tumor, targets are selected. After this, target-specific T-cells are isolated from the patient using the MACSQuant Tyto. In a subsequent T-cell priming and expansion phase, tumor-specific T cells expand to the kinds of numbers needed for cellular therapy. Finally, the T-cells are ready to be infused back into the patient and specifically combat malignant cells.

Importantly, Mohamed noted that the cell functionality of the sorted cells was preserved throughout, which is crucial in efficiently eliminating tumor cells.

“The gentle, microchip-based sorting mechanism preserves high viabilities among patients’ precious cells before they are moved to culture vessels for expansion,” said Mohamed.