Quantifying the biophysical properties of stomatocytes in health and disease
Authors: Zhaojie Chai, Jianlu Zheng, He Li, Ming Dao, George Em Karniadakis
Abstract
Hereditary stomatocytosis (HS) comprises red blood cell (RBC) disorders characterized by cup-shaped erythrocytes that respond oppositely to splenectomy: curative in overhydrated HS (OHS) but potentially thrombogenic in dehydrated HS (DHS/xerocytosis). This paradox persists because RBC biomechanics is governed by partly independent parameters--shear modulus, bending rigidity, surface-to-volume ratio (S/V), and cytoplasmic viscosity--that existing assays capture only piecemeal. Here we combine dissipative particle dynamics (DPD) simulations with microfluidic imaging to construct a control discocyte and three stomatocyte models (ST-RBC1-3) at fixed membrane area and decreasing volume (109.7, 101.5, 89.8 fL), spanning the OHS-to-DHS range. Tracing this parameter set through five mechanically orthogonal assays, we find that interendothelial-slit (IES) traversal is geometry-dominated: overhydrated ST-RBC1 requires an order of magnitude higher critical pressure than healthy RBCs, whereas dehydrated ST-RBC3 passes freely. ST-RBC3 nonetheless suppresses membrane tank-treading and raises low-shear whole-blood viscosity by ~29% at physiological haematocrit, comparable to Gaucher-disease hyperviscosity. A funnel-obstacle chip amplifies these differences into a label-free centerline-offset signal predicted to separate all four RBC types (~4.5 standard deviations between extreme phenotypes). These results unite single-cell mechanics, splenic filtration, and hemorheology in one framework, resolve the splenectomy paradox, and point toward microfluidic pre-operative risk stratification in HS.
Soft robotic systems are well suited for developing devices for biomedical applications. A bio-mimicking robotic soft esophagus (RoSE) is developed as an in vitro testing device of endoprosthetic stents for dysphagia management. Endoprosthetic stent placement is an immediate and cost-effective therapy for dysphagia caused by malignant esophageal strictures from esophageal cancer. However, later stage complications, like stent migration, could weaken swallow efficacy in the esophagus. The stent radial force (RF) on the esophageal wall is pivotal in avoiding stent migration. Due to limited randomized controlled trials in patients, stent design and stenting guidelines remain incomplete. To address this knowledge deficit, we investigate RoSE by implanting two stents (A and B) of different radial stiffness characteristics, to measure stent RF and its effect on migration. Endoscopic manometry under peristalsis is also performed to study the impact of stenting and stent dysfunction on intra-bolus pressure signatures (IBPSs) and swallowing efficacy. Each implanted stent undergoes experiments with varied peristalsis velocity, wavelength, and bolus concentrations. The results show that stiffer stent B has a higher RF, whereas stent A maintains a lower RF profile due to lesser stiffness. High RF is necessary to minimize migration under prolonged peristaltic contractions in RoSE. For manometry, stent A slightly increases IBPS, but stiffer stent B significantly decreases IBPS, especially for higher-concentration boluses. If a stiffer stent buckles, it can reduce swallow efficacy and cause recurrent dysphagia. RoSE is therefore an innovative soft robotic platform for testing endoprosthetic stents and addressing clinical challenges in stent evaluation.
Dipankar Bhattacharya, Sherine Jesna V. A., Leo K. Cheng +1
Deformability cytometry (DC) is a type of imaging flow cytometry, which uses a camera-equipped device to measure cellular stiffness in addition to other cellular properties at high throughput. Cellular properties such as area and elongation can identify cell types, but this requires prior knowledge of distinguishing properties and cannot be applied to clinically important cell aggregates. Using DC data, we evaluated conventional multi-class (MC) classification and introduced a multi-label (ML) approach for identifying blood cells and their aggregates. In particular, an ML classifier can simultaneously assign multiple cell-type labels to a single imaged event. We show that, unlike MC classification, ML classification can identify cell aggregates not represented in the training data. It also avoids the need for exhaustive, strictly defined aggregate labels, thereby simplifying and speeding up annotation. Since automated blood analyzers do not reliably analyze cell aggregates, our approach may help address this clinical gap.
Haptic rendering of viscoelastic materials that exhibit creep and stress relaxation is crucial for many applications, such as medical training with realistic biological tissue models. Fractional-order viscoelastic models provide an effective means of describing intrinsically time-dependent dynamics with few parameters, as these models can naturally capture memory effects. In this study, we present analyses of passivity and rendering performance for fractional-order viscoelastic models under finite-memory discretization. We derive closed-form expressions to ensure the passivity of haptic rendering with a fractional-order (FO) standard linear solid (SLS) model based on Grunwald-Letnikov derivative under short-memory discretization. We also provide symbolic expressions for the effective stiffness and damping of such FO-SLS models. The resulting passivity conditions constitute a unified framework that generalizes previously reported results for integer-order Kelvin-Voigt, Maxwell, and SLS models, since these results are special cases of the newly derived condition. Furthermore, we provide experimental validations of the theoretical passivity bounds and human-subject evaluations of perceived realism of FO-SLS models. Overall, this study establishes a unified theoretical framework and experimental evaluations for FO viscoelastic rendering under short-memory discretization.