Single cell mechanodeformation signatures as early biomarkers for hematological malignancies.

Abstract

Single-cell mechanical profiling of deformations has become a promising method of identifying a functional biomarker in patients with blood cancers. By quantifying the physical and mechanical properties of individual cells, this method examines the biomechanical changes that occur after alterations in the structure of the cytoskeleton, as well as changes occurring within the nucleus or chromatin as it relates to being transformed by cancerous processes. Mechanodeformation signatures provide a unique, universally applicable, and label-free measure of cellular states; therefore, they provide a different methodological category compared with traditional approaches such as immunophenotyping and molecular assays. This article critically reviews the mechanobiological basis for deformation and describes and compares quantifiable measurement parameters of deformation (stiffness, deformation index, recoverability, and transition dynamics) as well as a comparison between traditional methods of deformability analysis with microfluidic technologies, including their respective analytical performance, throughput, and clinical readiness. Relevant data will be summarized for each of the three leukemias, multiple myelomas and lymphomas examined, with an emphasis on study design, sample size, and validation of mechanism based on established criteria of measurable outcomes. We will also discuss how clinical applications such as early diagnosis, risk stratification, treatment response analysis, and monitoring of people with minimal detectable percentile changes (MRD) can all be done in a clinical setting. A special emphasis will be placed on pre-and post-analytical variables, standardization, quality control, and reproducibility, all critical to successfully implementing laboratory assessments. Additionally, we will examine different levels of variation (e.g., biological heterogeneity, cross-platform comparison, bias due to artificial intelligence, and regulatory requirements). Current research supports biological plausibility and discrimination within studies; however, large-scale multi-site validation and harmonized reporting standards must still happen before establishing routine use. The development of mechanodeformation signatures will create the opportunity for it to be integrated into current functional imaging tests used as a standard metric with regular measurements being taken over time. This ongoing study will serve to expand the current utilization of single-cell biomechanical phenotyping to improve personalized/precision-based medicine within the field of hematology.