Microfluidic Multi-Organ Platform for In-Vivo PK/PD Modeling
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing pharmacokinetic and pharmacodynamic models fail to accurately replicate in vivo biological systems, particularly in the study of organ-specific contributions and organ-to-organ crosstalk, and lack the ability to efficiently simulate mechanical cues such as fluid shear stress, leading to inaccurate pre-clinical drug development predictions.
Innovation Solution
A multi-MPS platform is designed with interconnected organ constructs that replicate in-human PK/PD profiles through optimized flow channels and fluid shear stress, incorporating biosensors for PD response monitoring, and utilizing machine learning for in-vitro to in-vivo translation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional pharmacokinetic and pharmacodynamic models are used, then the study of organ-specific contributions and organ-to-organ crosstalk is limited, but the complexity of accurately replicating in vivo biological systems increases
Solution Approach 1:
The system divides the biological system into discrete organ constructs (liver, kidney, heart, etc.) that can be individually cultured and then interconnected. Each organ construct is a separate module containing specific cell types and microenvironment, allowing complex in vivo systems to be broken down into manageable, studyable units while maintaining physiological relevance.
Solution Approach 2:
Microfluidic channels serve as intermediaries that connect discrete organ constructs and enable controlled fluid flow between them. These channels replicate blood vessel functions, allowing nutrients, drugs, and signaling molecules to flow between organ constructs while enabling precise control over flow rates and concentration gradients that would be difficult to achieve in traditional models.
2Ease of operation
If conventional models are used for pre-clinical drug development, then the study of mechanical cues such as fluid shear stress is insufficient, but the accuracy of drug development predictions decreases
Solution Approach 1:
The system uses microfluidic hydraulic flow to deliver nutrients and drugs to organ constructs while simultaneously applying physiological shear stress to endothelialized channels. The flow rates and pressures are controlled to replicate in vivo hemodynamic conditions, enabling study of mechanical cues' effects on organ function and drug response without requiring complex external mechanical stimulation devices.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The multi-MPS platform provides more accurate in-vitro results that translate to predicted in-vivo outcomes, enabling optimized drug dosing regimens and faster PK/PD analysis, while simulating mechanical cues relevant to human physiology.
Implementation Method 1
The resulting MPS platform includes either single pass flow channels or recirculating flow channels (or a combination of both) that facilitate the application of fluid shear stress to at least some of the MPSs
Implementation Method 2
channels that connect each MPS with at least one other MPS to facilitate a continuous circulated flow of a drug between the MPSs
Data Source
AI summary
Microfluidic platforms including multiple microphysiological systems. At least one of the platforms include: at least one inlet; a plurality of organ constructs, each organ construct of the plurality of organ constructs being sized relative to other organ constructs of the plurality of organ constructs based on at least one predetermined human pharmacokinetic (PK) parameter; and a plurality of channels, each channel of the plurality of channels causing an organ construct of the plurality of organ constructs to be in fluidic communication with at least one other organ construct of the plurality of organ constructs.