Mohammad Ameen Qasaimeh

Cancer progression is shaped by coupled molecular, biochemical, and mechanical changes across multiple scales, from altered signaling and cytoskeletal organization to cellular deformation, adhesion, and metastatic dissemination. Circulating tumor cells (CTCs) are rare and heterogeneous in blood, occurring as single cells and multicellular clusters that provide access to evolving tumor phenotypes through liquid biopsy. Their apparent elasticity, deformability, adhesion, and viscoelastic behavior may reflect invasive potential, treatment response, and phenotypic state, while cytoskeletal proteins, membrane lipids, cell surface glycans, and receptors provide molecular context for these mechanical signatures. This review examines the complementary roles of microfluidics and atomic force microscopy (AFM) in multiscale CTC mechanobiology. Microfluidic platforms support label-free and affinity-based enrichment, capture, positioning, and recovery of viable cells. AFM provides localized measurements of apparent elasticity, deformation, adhesion, viscoelastic response, and nanoscale surface architecture in liquid, while functionalized probes enable molecular recognition and molecule-specific force measurements. We evaluate physical, affinity-based, cluster-preserving, open-space, and artificial intelligence-assisted microfluidic strategies together with reversible device assembly, automated AFM targeting, fluidic probes, advanced mapping modes, and treatment-response applications. Existing studies establish feasibility, including direct AFM measurements of individual patient-derived CTCs and automated analysis following microfluidic enrichment in model rare-cell mixtures. Clinical evidence remains limited, many integrated workflows rely on cultured cells or spiked samples, and within the literature identified in this review, direct AFM characterization of intact patient-derived CTC clusters was not found. Clinical translation will require confirmation of tumor identity, standardized acquisition, analysis, and reporting, increased throughput, statistical analysis that preserves the hierarchy of patients, cells, and force curves, and validation in independent patient cohorts. Integrated AFM-microfluidic platforms could extend CTC liquid biopsy beyond enumeration toward functional mechanobiological analysis relevant to metastasis, therapeutic response, and biomarker development.

Plug-and-play IPOF microfluidics converts open-space flows into addressable chemical nodes for programmable reagent delivery, gradient discretization, and multiplexed surface patterning.

Adoptive T cell therapy for solid tumors is limited by poor persistence of CD8+ T cells, a dysfunction that is often programmed during ex vivo expansion. Here, we show that, when biochemical inputs are held constant,substrate mechanics alone can direct durable anti-tumor function in primary human CD8+ T cells. Using polyacrylamide (PA) hydrogels of defined stiffness (soft ~1 kPa; stiff ~55 kPa) in both flat and bead formats, we first establish that contact geometry dominates early activation, whereas substrate stiffness governs the 14-day expansion trajectory. Across the rapid expansion protocol, flat PA substrates sustain proliferation, limit PD-1/LAG-3 acquisition, and preserve a balanced effector-regulatory cytokine profile. In contrast, Dynabeads™-expanded cells exhibit net cell loss and a more pronounced decline in cytokine output over time. To define the underlying programs, RNA-seq identifies a 125-gene biomimetic core shared by both PA conditions but absent from Dynabeads™, encompassing proliferation, OXPHOS, mechanobiology, and a stem-like precursor (Tpex) signature. Consistent with these transcriptional differences, metabolic profiling shows that flat soft PA best preserves dual glycolytic and mitochondrial capacity at day 14, indicating enhanced bioenergetic flexibility. Functionally, PA-primed CD8+ T cells display superior cytotoxicity against MDA-MB-231 and MCF-7 breast cancer cells in both 2D and collagen-based 3D co-cultures, with this advantage maintained under matrix constraints that mimic solid tumor microenvironments. Together, these findings establish substrate mechanics as a tunable and functionally decisive design parameter for engineering durable, solid-tumor-effective CD8+ T cell products in preclinical in vitro models of solid tumors.

This work presents the design, fabrication, and characterization of multichannel soft microfluidic force sensors for integration with laparoscopic graspers. The sensors consist of PDMS structures encapsulating Galinstan-filled microchannels, where applied forces induce structural deformation and a corresponding increase in electrical resistance. Fabrication is achieved through 3D printing and PDMS molding under cleanroom-free conditions, enabling cost-effective and reproducible sensor production. We systematically investigated key design parameters, including microchannel geometry and sensor thickness and stiffness, through finite element simulations and experimental validation. Results show that thinner, softer sensors with inverted stepped-triangle microchannels exhibit the highest sensitivity. To further extend functionality, we developed both multilayer and coplanar multichannel sensor designs, enabling dual-range sensing with improved linearity and tunability. The sensors were integrated into a laparoscopic grasper, with one sensor mounted on the handle to measure thumb-applied actuation forces and another sensor on the jaw to capture tissue contact forces. This dual-sensing configuration highlights the potential of soft microfluidic sensors to restore tactile feedback in minimally invasive surgery. Overall, microfluidic technology provides a practical, scalable approach to soft-sensing systems for surgical tools, robotics, and human-machine interfaces.

Microfluidic probes (MFPs) are an emerging class of open microfluidic devices that use hydrodynamic flow confinement (HFC) to enable precise, contact-free delivery and removal of fluids on biological surfaces.

Three-dimensional in vitro tumor models are increasingly recognized for their value in preclinical oncology, offering enhanced physiological relevance compared to traditional two-dimensional cultures. These systems improve the reliability of drug response assessment and hold potential for advancing patient-specific treatment strategies. In this work, we introduce the Spheromatrix, a paper-based platform designed to support spheroid formation, long-term preservation, and parallelized drug evaluation. This scalable system maintains the viability, proliferation, and metabolic activity of tumor spheroids across a variety of cancer cell lines, including U87 glioblastoma. Importantly, it supports cryopreservation and subsequent re-culture, potentially enabling the generation of pre-formed, ready-to-use 3D tumor models. Drug testing on U87 spheroids revealed consistent cytotoxic effects of cisplatin and temozolomide (TMZ), both as single agents and in combination, before and after cryostorage. Combined treatment amplified cytotoxic outcomes, indicating a potentiating effect of cisplatin on TMZ-induced cell death. These results position the Spheromatrix as a practical and versatile platform for building 3D tumor model biobanks and addressing critical gaps in current model accessibility and reuse.

Population density plays a critical role in microbial fitness, yet its influence on pathogen colonization and persistence remains incompletely understood. Porphyromonas gingivalis (Pg) exhibits Allee-type growth, requiring a quorum threshold to replicate, yet is frequently detected at low abundance in vivo. We integrate quantitative growth experiments with mathematical modeling to identify ecological and stochastic determinants of Pg persistence. A cubic Allee-effect model quantifies a quorum threshold below which populations collapse, while conditioned medium from Veillonella parvula (Vp) lowers this threshold, indicating early-colonizer facilitation. Stochastic extensions and Fokker–Planck analysis show that microenvironmental noise enables escapes across the Allee barrier, consistent with long-term subthreshold experiments yielding a stationary, powerlaw–like distribution and under-threshold survival. Pg–Vp co-cultures further demonstrate replicate rescue outcomes for subcritical inocula. Critically, Vp reliably saturates to capacity, constraining terminal phases within the experimental horizon to coexistence (Pg persists with Vp at capacity) or Pg extinction . A two-species replicator model maps these outcomes onto a ( β, γ ) plane, restricting accessible regions once Vp is established and suggesting interventions that reduce facilitation or variability to restore eubiosis and limit Pg-associated inflammation.

The study presents the development of a radially compartmentalized paper chip (RCP‐Chip) designed for the rapid detection of multiple gene targets of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) using reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) assay. The RCP‐Chip features reaction chambers for multiplexing, fluidic resistors to prevent backflow, fluidic ports for excess fluid venting, and an outer ring to contain overflowing fluids, all within a single‐layer cellulose paper platform. Optimization results successfully achieve a color readout sensitivity of 10 copies µL⁻¹ RNA spiked in water (singleplex device) and 2040 copies µL⁻¹ RNA spiked saliva samples (multiplex device). The chip demonstrates the capability to simultaneously detect the envelope (E) and nucleocapsid (N) genes of SARS‐CoV‐2 in a single run. Remarkably, the RCP‐Chip technology enables rapid qualitative amplification of SARS‐CoV‐2 RNA in as little as 4 min using pH‐based assay. It further enhances this visual detection by implementing in situ synthesis of gold nanoparticles (AuNPs) within the single‐layer paper platform, achieving a total assay time of 9 min. The adaptability of RCP‐Chip can extend beyond SARS‐CoV‐2 detection: It can be modified and optimized for detecting gene targets of other microbial pathogens across diverse environments pertaining to cause diseases.

The missing tactile sensation in minimally invasive surgery (MIS) presents significant challenges and safety risks in routine surgical procedures. Previous attempts to integrate tactile sensors onto the jaws of surgical tools encountered issues with sterilization, biocompatibility, and wiring complexities. This work introduces a novel “off-the-jaw” (OTJ) tactile sensing system, which tackles these limitations by integrating force and angle sensors onto the handle of MIS instruments to indirectly measure the grasping force and angle during tissue palpation while preserving the original design and functionality of the grasping jaws. A prototype was developed using a force-sensitive resistor and a rotary potentiometer integrated onto the handle of a laparoscopic grasper. Real-time data processing provides user-friendly visual feedback on tissue thickness and stiffness. Testing was performed using soft elastomeric samples designed to mimic human tissues of varying sizes and stiffness. Initial validation demonstrated a strong correlation between the force applied by the user’s thumb on the handle and the force exerted by the grasping jaws on the samples. The sensor-equipped handle successfully differentiated samples based on thickness and stiffness and integrated seamlessly with various surgical end effectors in a plug-and-play manner. Pre-clinical trials with both regular and surgical users revealed significant improvements in sample sorting and lump detection tasks, with up to 30% increase in speed and accuracy. The OTJ technology holds promising potential to improve surgical precision and patient care by restoring tactile feedback in MIS, ultimately contributing to safer and more effective surgical practices.