High-Throughput Cell Screening With Interferometric Cytometry (Case No. 2007-720)

Summary

The combined technology platform encompasses optical cytometry via interferometric membrane probing and cell mechanical / membrane property characterization, using reflective microparticles and interferometric imaging to measure deformation and viscoelastic response of live cells. The approach links physical membrane dynamics to cellular state, enabling label-free diagnostics, mechanical phenotyping, or response monitoring. One of the patents (US 10,802,012 B2) applies interferometry with microparticles to observe membrane motion in response to magnetic actuation to infer cell viscoelastic properties and physiological state.

Background

Understanding mechanical and morphological properties of cells is increasingly important in diagnostics, drug screening, and cell biology. Traditional methods (e.g. micropipette aspiration, atomic force microscopy, traction force microscopy) are often low throughput, invasive, or require specialized instrumentation. Meanwhile, many optical cytometry techniques focus on fluorescence markers or bulk properties, lacking direct access to mechanical responses. There is a need for non-invasive, label-free, high-throughput methods that can probe mechanical and viscoelastic properties of cell membranes and correlate them to cell phenotype or response.

Innovation

• The patents introduce a method in which reflective microparticles (such as magnetic micromirrors) are adhered to or placed proximate to the cell membrane.

• The system uses interferometry (e.g. Michelson or similar configurations) to measure sub-nanometer displacements or motion of these microparticles in response to applied stimuli (e.g. magnetic force) or environmental perturbations.

• By analyzing the motion (amplitude, phase, dynamics) of the microparticles and relating them to applied force, the membrane mechanical properties, viscoelasticity, cell stiffness, or response dynamics can be inferred.

• The invention enables real-time or dynamic measurement of membrane movement and can correlate those mechanical properties to cellular states (e.g. healthy vs pathological, response to drugs).

• One embodiment involves applying a magnetic field to drive motion of the reflective microparticles, and observing the resulting membrane dynamics optically.

• The method is suited to measuring characteristics such as cell optical thickness, membrane displacement, mechanical deformation, or changes over time following stimuli.

Advantages

• Label-free mechanical phenotyping: does not rely on fluorescent dyes or genetic labels.

• High sensitivity: interferometric detection enables very fine displacement measurement (sub-nanometer).

• Potential throughput: integrated with optical cytometry, can analyze many cells in sequence.

• Non-destructive: minimal mechanical intrusion, preserving cell viability in many cases.

• Multiparametric: can measure both optical (thickness, refractive index) and mechanical (viscoelastic response) properties simultaneously.

• Correlative diagnostics: mechanical signatures can complement or even precede morphological or molecular markers.

Potential Applications

• Diagnostic assays where mechanical phenotype is indicative (e.g. cancer cell rigidity, metastatic potential).

• Drug screening: measuring how candidate compounds alter cell mechanics or membrane properties.

• Cell sorting or phenotyping platforms that incorporate mechanical contrast as a sorting criterion.

• Fundamental cell biology research: investigating mechanotransduction, membrane cytoskeleton integrity, or response to mechanical stimuli.

• Monitoring of cell state transitions (e.g. apoptosis, differentiation) via mechanical signature.

• Integration into optical cytometry devices (flow or static) for combined mechanical + optical characterization.

Patent / Applications

• US 10,802,012 B2 — Optical Cytometry to Determine Cell Characteristics via Membrane Interferometry & Microparticles Google Patents

• US 8,599,383 B2 — Optical Cytometry Google patents

• US 9,810,683 B2 — Use of live cell inteferometry with reflective floor of observation chamber to determine changes in mass of mammalian cells Google patents\