dFC: Digital Flow Cytometry

Absolute Quantitation with Single-Molecule Counting

from biomolecules to biological nanoparticles

Digital Flow Cytometry (dFC)

Flow cytometry forbiological moleculesand nanoparticles

From affinity profiling and QC of therapeutic and research antibodies to multiparameter characterization of biological nanoparticles such as EVs, LNPs, and viral vectors

Antibodies
EVs
LNPs
Viral vectors
Pangnostics PanView digital flow cytometer, shown in a front three-quarter studio rendering.

Pangnostics’ PanViewTM digital flow cytometer (dFC) employs planar microfluidics to enable 100% single-fluorophore detection at high particle throughput, enabling greater sensitivity and capabilities than conventional macrofluidic flow cytometers.

THE PARADIGM SHIFT

Turning flow cytometry upside down.

Conventional nanoscale flow cytometers use a top-down approach in which technologies developed for cells were adapted for nanoparticles.Pangnostics takes a bottom-up approach that starts with single-molecule detection (SMD).

CONVENTIONAL FLOW CYTOMETRY

  • Macrofluidic sheath-flow systems
  • Insufficient sensitivity to detect every fluorophore
  • Cannot detect single molecules or small EVs
  • Quantitation requires external calibration

PANGNOSTICS dFC

  • Planar microfluidic system
  • 100% single-fluorophore sensitivity
  • Detects every fluorescent biomolecule or particle
  • Absolute quantitation via single-molecule counting
Scientific size spectrum showing LOD of current nanoscale flow cytometers
LOD of current nanoscale
flow cytometers
Scientific size spectrum showing LOD of dFC (100% fluorophore detection)
LOD of dFC
(100% fluorophore detection)

HOW dFC WORKS

Making every molecule count

Explore how dFC detects every fluorescent molecule.

Watch how individual counts become a distribution.

Because fluorophore emission is stochastic, the detected photon bursts can vary widely from one fluorophore to another. The high sensitivity of dFC ensures the detection of even the dimmest fluorophore population.

WHY dFC

Unparalleled sensitivity.
12-color detection.

Absolute quantitation

Count fluorescent molecules and particles directly, without external calibration

Single-molecule sensitivity

Detect biological molecules and nanoparticles that conventional flow cytometers miss

Deep phenotyping of EVs and other biological nanoparticles

Four excitation lasers and 12 detection channels enable detection of up to 12 biomarkers, corresponding to ~4000 possible EV subpopulations.

High throughput

The high spatial resolution of dFC minimizes coincident detection (swarming), improving the accuracy of quantitation and enabling high particle throughput, with data acquisition at 10 kHz.

Applications

Conceptual antibody illustration

Antibody QC

Absolute concentrations, F:P, KD, aggregate detection

Learn more
Conceptual translucent extracellular vesicle illustration

EV analysis

Deep phenotyping, biomarker copy numbers, subpopulation concentrations

Learn more
Conceptual lipid nanoparticle cutaway illustration

Lipid nanoparticles

Encapsulation efficiency and payload-positive fraction

Coming soon
Conceptual viral vector illustration

Viral vectors (e.g., AAVs)

Full/empty capsid ratio and genome-containing particle fraction

Coming soon

SINGLE-MOLECULE ANALYSIS

Antibody analysis by dFC:

Absolute antibody concentrations

Direct, quantitative measurements

Fluorophore-to-protein ratio (F:P) (degree-of-labeling)

QC of antibody-dye conjugates used in research

Binding affinity (KD)

Rapid screening of labeled and unlabeled therapeutic and research antibodies

Aggregate detection

For labeled and unlabeled therapeutic and research antibodies

Watch an overview of
antibody analysis

SINGLE-PARTICLE ANALYSIS

Single-EV analysis by dFC:

  • 12-channel biomarker analysisSimultaneous detection of multiple EV surface and cargo markers.
  • EV phenotypingIdentify and characterize distinct EV subpopulations.
  • Absolute concentrations of EV subpopulationsDirect, quantitative measurements.
  • Absolute quantitation of biomarker copy numbersSingle-molecule sensitivity enables copy number measurements by digital deconvolution.
  • EV sizing based on a membrane dyeDetermine EV size distributions using a lipid membrane dye.

SINGLE-PARTICLE ANALYSIS

Phenotyping individual EVs

With 4 excitation lasers and 12 color channels, dFC can unmask the biological heterogeneity of biomedical nanoparticles such as EVs in a single experiment—down to the smallest nanoparticle.

Video preview
Eight-marker single-EV heatmap with an expanded view of EVs 500–600

SINGLE-PARTICLE ANALYSIS

Absolute concentration measurements

Direct counting of fluorescent antibodies or EV subpopulations

By detecting every molecule that flows through the channel, dFC achieves absolute quantitation of the concentration of fluorescently-labeled biomolecules or EV subpopulations.

Tumor-cell-derived EV subpopulation concentrations and measured EV concentration across dilution factors

SINGLE-PARTICLE ANALYSIS

Absolute quantitation of biomarkers

The ultra-high sensitivity of dFC enables single-molecule counting of protein and nucleic acid biomarker copy numbers associated with each EV—without external calibration.

Video preview
Watch how single-EV biomarker copy numbers are calculated using digital deconvolution

A CLOSER LOOK

Follow an EV through the dFC PanFlow™ Chip.

Video preview

Eight-marker EV heatmap

Eight-marker single-EV heatmap with an expanded view of EVs 500–600