Cellularized Nephron Unit for Concentrated Urine

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Solution Overview

Problem

Existing artificial kidney devices fail to fully replicate the nephron's function, particularly in forming concentrated urine, leading to excessive waste generation and thrombogenicity, and require mechanical pumping for filtration.

Innovation Solution

A microfabricated, cellularized bioartificial device that mimics the Loop of Henle, distal tubule, and collecting duct, using a pressure gradient for filtration and cellular diffusion for re-absorption, eliminating the need for mechanical pumps and reducing thrombogenicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of substance

If conventional hemodialysis or hemofiltration is used for blood filtration, then waste removal is achieved, but excessive waste fluid is generated and plasma must be replaced

Engineering Contradiction:

Improvewaste fluid generationVSAvoidplasma replacement requirement

Core Design Contradiction:

Loss of substanceVSQuantity of substance

Solution Approach 1:

The invention segments the nephron function into distinct microfabricated modules: a glomerular filter module for pressure-driven filtration and a tubular module for active reabsorption. This segmentation allows selective reabsorption of plasma components back into the bloodstream, reducing waste fluid generation and eliminating the need for plasma replacement

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The device employs living renal cells within the tubular module that autonomously perform active transport and reabsorption functions. These cellular components self-regulate the reabsorption of water, electrolytes, and nutrients back into the blood, mimicking natural kidney function without requiring external plasma replacement

Inventive Principle:

Principle #25Self-service

2Reliability

If existing bioartificial kidney devices are used, then some reabsorption function is achieved, but the complete nephron function including concentrated urine formation is not replicated

Engineering Contradiction:

Improvenephron function replicationVSAvoiddevice structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention implements a nested structure where the tubular module is positioned within or adjacent to the glomerular filter module. The filtrate generated in the glomerular filter is directly channeled into the tubular module for reabsorption, creating a compact integrated unit that replicates the complete nephron pathway in a space-efficient manner

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The invention merges the filtration and reabsorption functions into a single integrated device. The glomerular filter and tubular module work together as a unified system, combining pressure-driven filtration with cellular active transport to achieve complete nephron function in one compact unit

Inventive Principle:

Principle #5Merging (Combining)

3Productivity

If mechanical pumping is used for blood filtration, then filtration flow is maintained, but thrombogenicity increases

Engineering Contradiction:

Improvefiltration flow rateVSAvoidthrombogenicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention replaces mechanical pumping with a pressure gradient-driven filtration system. Blood flows through the glomerular filter under a controlled pressure gradient, eliminating the need for mechanical pumps that cause shear stress and thrombosis. The pressure gradient is maintained through differential pressure between the blood inlet and filtrate outlet

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The device utilizes hydraulic pressure gradients to drive blood through the glomerular filter and filtrate through the tubular module. This hydraulic approach mimics natural kidney hemodynamics, maintaining physiological flow rates without mechanical intervention, thereby reducing thrombogenicity while preserving filtration productivity

Inventive Principle:

Principle #29Pneumatics and hydraulics

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 device effectively replicates kidney function, reducing waste generation and thrombogenicity, enabling the formation of highly concentrated urine without mechanical assistance, and can be used for both experimental and clinical applications.

Implementation Method 1

a pressure gradient is introduced across a mechanical filter to replicate the filtration step found in a kidney glomerulus

Methodology Applied

Scientific EffectPressure gradient: Pressure Gradient

Implementation Method 2

cellular diffusion for re-absorption

Methodology Applied

Scientific EffectDiffusion: Diffusion

Data Source

PatentUS8460546B2Systems, methods and devices relating to a cellularized nephron unit

Publication Date: 2013.06.11 THE CHARLES STARK DRAPER LABORATORY INC

AI summary

The present invention relates to bioartificial devices and systems that mimic kidney or nephron function and methods of making them.