Microfluidic Chips for Advanced Disease Models

BMSEED’s microfluidic chip is the first commercial microfluidic device that is both stretchable and allows for in-situ, real-time electrophysiological recording and stimulation. The critical technology to enable these capabilities is the integration of our stretchable microelectrode arrays (sMEAs) within the microfluidic chip. The chip consists of two concentric chambers that a separated by a microfluidic channel, and is interfaced via a cassette with the perfusion fluid handling system. It enables physiologically relevant disease modeling in three‐dimensional (3D) cell cultures. Designed specifically for preclinical studies for neurological and neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s Disease (PD), and traumatic brain injury (TBI), our platforms offer researchers an innovative tool for drug screening and mechanistic studies.

Introduction

Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) account for 50-75% of all dementia cases, and affects about 10% of people age 65 (14% for African Americans) and 50% over the age of 85. Currently available treatments for AD/ADRD patients only help manage the symptoms of the disease, but there is no cure. Without a treatment to stop or reverse the progression of the disease, the number of Americans living with AD/ADRD is projected to grow from 5.8 million today to 13.8 million by 2050.

BMSEED’s microfluidic chip addresses two major problems in developing treatments for AD/ADRD.

1) Gap between pre-clinical drug screening and clinical trials: A review has identified over 100 compounds with 40 different mechanisms of action that had been considered as potential treatments for AD/ADRD. Twenty of these compounds showed evidence of benefits in pre-clinical trials, but all candidates failed in Phase III clinical trials, and none was FDA approved. This failure clearly shows that current pre-clinical models of AD/ADRD are not adequate to predict clinical outcomes.

2) Interactions between genetic and environmental risk factors to develop AD/ADRD are poorly understood: Numerous studies found substantial epidemiological evidence that a history of traumatic brain injury (TBI) increases the risk to develop AD/ADRD later in life. Notably, the Amyloid β plaques that are produced following a TBI are similar to those observed in early stages of AD/ADRD. Furthermore, repetitive mild TBI may lead to permanent degenerative changes including chronic traumatic encephalopathy and Alzheimer’s disease. Other theories linking TBI and AD/ADRD are neuronal loss, persistent inflammation, and cytoskeletal pathology. Nevertheless, the complex relationship between AD/ADRD and TBI, as well as the role of genetics, is not fully understood.

BMSEED’s cutting-edge technology addresses these challenges by integrating:

• 3D Microfluidic Chip Design: Dual-chamber design with a precisely engineered microchannel with trapezoidal posts to allow controlled perfusion of nutrients, drugs, and biomarkers.

• Stretchable Microelectrode Arrays (sMEAs): Integrates stretchable electrodes with the microfluidic chip to enable in-situ, real time electrophysiological measurements of cell health and function.

• Integrated TBI Simulation: In conjunction with BMSEED’s MEASSuRE system, biomechanical stimuli such as those that reproduce the biomechanics of a TBI can be applied to the cells in the chip. The embedded stretchable electrodes enable electrophysiological assessments of cellular health and function before and after stretching.

Benefits

(1) The platform is not limited to a particular theory for AD pathogenesis, and all prevailing theories can be investigated: Aβ plaques, phosphorylated Tau fibrils, neuroinflammation, and vascular dysfunction.

(2) The two-chamber design enables the investigation of single cell types and of neuronal crosstalk with microglia and astrocytes, which is an important factor in mediating changes in neuronal electrophysiology, viability, and synaptic density.

(3) Cells from various sources can be investigated, e.g., from human induced-pluripotent stem cells (hiPSC) from healthy individuals and those with AD/ADRD, as well as from wild type and genetically modified animal models.

(4) The microfluidic channel between the two chambers allows to control the biochemical environment (nutrients, biomarkers, oxygen, drugs) in the cell culture, e.g., to reproduce conditions that cause vascular degeneration and neuroinflammation.

(5) The two chambers are filled with a 3D Matrigel matrix to more accurately represent the cellular environment in vivo compared to 2D cultures typically used in pre-clinical research.

(6) The microfluidic chip consists of soft materials, which more accurately mimics the environment in vivo than cell culture platforms made of plastic or glass.

(7) BMSEED’s proprietary soft and stretchable electrodes are embedded in the platform and enable the functional assessment of neuronal health in situ.

(8) The tool replicates the biomechanics of a TBI by mechanically deforming the cells on the microfluidic chip. The embedded soft, stretchable electrodes enable the direct assessment of the neuronal health and function before and after the injury.

Applications

BMSEED’s microfluidic devices are designed to serve multiple research needs:

• Preclinical Drug Screening: Rapid, high-throughput testing of candidate compounds in a model that closely mimics the in vivo environment.

• Mechanistic Studies: Investigation of the pathological processes behind AD/ADRD, including amyloid beta (Aβ) plaque formation, tau pathology, neuroinflammation, and vascular dysfunction.

• TBI-AD/ADRD Interface: Explore the complex relationship between mechanical brain injury and subsequent neurodegeneration.

• Broader Neurodegenerative Research: Although focused on AD/ADRD, the technology is readily adaptable to studies in other neurological disorders such as Parkinson’s disease.

Technology & Innovation

BMSEED’s innovation lies in our unique ability to combine advanced microfabrication techniques with biological expertise in cell culturing:

• Stretchable Electrode Technology:
  Our microelectrodes, which maintain function even at high strains (up to 50%), allow for realistic simulation of both physiological and pathological mechanical deformations.

• 3D Microfluidic Integration:
  The dual-chamber system mimics in vivo cellular environments by ensuring controlled perfusion and diffusion of key molecules.

• Modular Design:
  The platforms are engineered for scalability — from single-well devices for detailed mechanistic studies to multi-well systems for high-throughput applications.

• Versatile Cell Compatibility:
  Supports experiments with mouse-derived cells, human induced-pluripotent stem cell (hiPSC) derivatives, and co-culture systems to study neuron–glia interactions in a 3D context.

Benefits for Researchers

• Physiological Relevance:
  3D cell cultures provide a more accurate representation of in vivo conditions compared to traditional 2D models.

• Comprehensive Readouts:
  Integrated electrophysiology and imaging capabilities allow for simultaneous monitoring of functional and structural changes.

• High-Throughput Capability:
  Multi-well systems enable parallel experiments, significantly accelerating the pace of discovery.

• Customizable Protocols:
  Whether you are investigating basic cellular mechanisms or screening potential therapeutics, BMSEED’s platforms can be tailored to your experimental needs.

Frequently Asked Questions About our Microfluidics Module

1. What is BMSEED’s Microfluidics Module?

The Microfluidics Module is an advanced 3D cell culture system that integrates BMSEED’s stretchable microelectrode arrays (sMEAs) with a microfluidic channel to simulate the in vivo cellular environment in the brain to study neurological and neurodegenerative diseases. This module can be used separately or concurrently with BMSEED’s MEASSuRE system, which integrates a cell stretcher with electrophysiology and imaging to simulate the in vivo biomechanics.