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HD-DoE®
Technology Platform

Controlling the fate of a cell

Our HD-DoE (high-dimensional design-of-experiments) technology is a powerful platform that extracts conditions for making all types of specialized human cells, including neurons, insulin cells, endothelial cells, pigment epithelium, collecting duct cells, and bronchiolar cells to name a few. Trailhead Biosystem’s HD-DoE platform addresses the optimization challenges around cell purity and potency to understand the variance in cell manufacturing methods.

We use computerized DoE, executed through robotic media preparation, to test the entirety of a multidimensional factor space. We then use Multi-Variate Data Analysis to mathematically model differentiation and identify optimal conditions for reaching specific cell fates.

The Trailhead Biosystems® Difference

Traditional Black-Box Biology

  • Single factor optimization, highly iterative process.
  • Experiments designed and limited by the human mind.
  • Cell culture is done by hand and prone to error.
  • Results are limited to the original design.

Trailhead® Systems Biology

  • Efficient, multi-dimensional experiments.
  • Experiments are designed with proprietary mathematical software.
  • Robots perform precise, scalable experiments.
  • Design enables results to be used in virtual experiments.

Our HD-DoE platform allows us to build protocols for making specialized human cells from iPSCs:

Built from Scratch

All protocols are based on unique stage-inducing media, not copied from literature or existing IP

Data, Not Hypothesis, Driven

All protocols are based on empirical data obtained from using HD-DoE

Validation

All protocols are validated through molecular and histological attributes that are respected and qualified by literature

Quality by Design

All protocols adhere to a Quality-by-Design standard, for all stages

Critical Process Parameters

All protocol inputs are statistically qualified as Critical Process Parameters

Close-to-Absolute-Conversion

All protocols are developed to maximize purity, seeking to attain Close-to-Absolute-Conversion to the desired fate

Universality

Our protocols typically achieve consistent differentiation regardless of iPSC line/clonal origin

Mathematics: Meet Biology

We attain response modeling of key cellular parameters through highly dimensioned experiments.

We merge developmental biology with cutting-edge hardware and computerized experimental design and analysis to perform process-specific parameter optimization in order to develop cell therapies. Our HD-DoE (high-dimensional design-of-experiments) platform is unique. We are pushing the boundaries of dimensional testing to speak with, and control, biology.

We use computerized DoE, executed through robotic media preparation, to test the entirety of a multidimensional factor space. We then use Multi-Variate Data Analysis to mathematically model differentiation and identify optimal conditions for reaching specific cell fates.

Our HD-DoE platform allows us to build protocols for making specialized human cells from iPSCs:

Organization

iPSC-derived neurons assemble into morphological structures and extend their neurites across open spaces.

Oligodendrocytes

Trailhead iPSC-derived Oligodendrocytes, O4 staining (green). Oligodendrocytes insulate the nerve connections in the brain.

Good Neighbors

Fields of oligodendrocyte progenitor cells establish cell-cell connections through GAP-junctions.

Forebrain Interneurons

Trailhead iPSC-derived Forebrain Interneurons, TUJ1 staining

Forebrain Interneurons

Interneurons modulate the excitatory activity of glutamatergic neurons. Trailhead iPSC-derived forebrain interneurons. GABA staining.

Parvalbumin+ Interneurons (MGE)

Trailhead iPSC-derived interneurons, PVALB staining

Midbrain

Trailhead iPSC-derived neurons, TUJ1 staining

A Sense of Direction

Newly-born TUJ1+ neurons arrange longitudinally.

Synapsin

Functional iPSC-derived neurons assemble in neural networks – they extend axons, generate and store synaptic vesicles.

Endothelial Pockets

Endothelial cells from iPSCs form endothelial pockets.