Quantitative Deformability Cytometry: Rapid, Calibrated Measurements of Cell Mechanical Properties.

Advances in methods that determine cell mechanical phenotype, or mechanotype, have demonstrated the utility of biophysical markers in clinical and research applications ranging from cancer diagnosis to stem cell enrichment. Here, we introduce quantitative deformability cytometry (q-DC), a method for rapid, calibrated, single-cell mechanotyping. We track changes in cell shape as cells deform into microfluidic constrictions, and we calibrate the mechanical stresses using gel beads. We observe that time-dependent strain follows power-law rheology, enabling single-cell measurements of apparent elastic modulus, Ea, and power-law exponent, ß. To validate our method, we mechanotype human promyelocytic leukemia (HL-60) cells and thereby confirm q-DC measurements of Ea = 0.53 ± 0.04 kPa. We also demonstrate that q-DC is sensitive to pharmacological perturbations of the cytoskeleton as well as differences in the mechanotype of human breast cancer cell lines (Ea = 2.1 ± 0.1 and 0.80 ± 0.19 kPa for MCF-7 and MDA-MB-231 cells). To establish an operational framework for q-DC, we investigate the effects of applied stress and cell/pore-size ratio on mechanotype measurements. We show that Ea increases with applied stress, which is consistent with stress stiffening behavior of cells. We also find that Ea increases for larger cell/pore-size ratios, even when the same applied stress is maintained; these results indicate strain stiffening and/or dependence of mechanotype on deformation depth. Taken together, the calibrated measurements enabled by q-DC should advance applications of cell mechanotype in basic research and clinical settings.

Adjuvant high dose rate brachytherapy for soft tissue sarcomas: initial experience report.

PURPOSE: Adjuvant high-dose-rate brachytherapy (HDRBT) offers advantages over low dose rate brachytherapy (LDRBT), although there are little data on local tumor control and treatment related toxicity. We report outcome in patients with primary, recurrent, and metastatic extremity and superficial trunk soft tissue sarcoma. MATERIAL AND METHODS: Eleven patients (12 sites) with intermediate or high grade sarcoma were treated with adjuvant HDRBT following surgical resection. Patients were treated at 3.4 Gy fractions delivered twice daily to a total dose of 34 Gy (1 patient received 9 fractions). RESULTS: With median follow-up of 20.8 months, 1 patient developed a local recurrence. 2-year local control and overall survival are 89% and 71%, respectively. Wound complications occurred in 3 sites. Two of the wound complications developed in the area of previous external beam radiotherapy (EBRT). CONCLUSION: Surgical resection followed by HDRBT is associated with excellent early local tumor control and acceptable wound complication.