Metal-Organic Framework Adsorbents for Protein-Bound Uremic Toxins

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Solution Overview

Problem

Conventional extracorporeal renal replacement therapies are ineffective in removing protein-bound uremic toxins due to poor diffusion, and existing adsorbents lack high selectivity and fast kinetics for uremic toxin removal.

Innovation Solution

The use of metal-organic frameworks (MOFs) with zirconium-based nodes and specific organic linkers, such as NU-1000, that facilitate π-π binding and electrostatic interactions for efficient adsorption of uremic toxins, including p-cresyl sulfate, indoxyl sulfate, and hippuric acid, from biological samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional extracorporeal renal replacement therapies by diffusion are used, then the therapy is simple to operate, but the removal of protein-bound uremic toxins is poor

Engineering Contradiction:

Improveremoval of protein-bound uremic toxinsVSAvoiddiffusion-based therapy simplicity

Core Design Contradiction:

Quantity of substanceVSEase of operation

Solution Approach 1:

The patent employs metal-organic frameworks (MOFs) as porous adsorbent materials with controlled pore sizes and high surface areas. These MOFs are specifically designed to adsorb protein-bound uremic toxins from blood, achieving superior removal efficiency compared to conventional diffusion-based methods while maintaining operational simplicity through their porous structure

Inventive Principle:

Principle #31Porous materials

Solution Approach 2:

The invention uses composite metal-organic framework materials that combine organic linkers with metal clusters to create a material with tailored properties. These composite MOFs exhibit enhanced affinity and selectivity for protein-bound uremic toxins, resolving the contradiction between removal efficiency and operational simplicity

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If activated carbon zeolites and composite membranes are used as adsorbents, then the adsorbent capacity is improved, but the selectivity and kinetics for uremic toxin removal are insufficient

Engineering Contradiction:

Improveadsorbent capacityVSAvoidselectivity and kinetics

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent applies local quality by functionalizing specific regions of the MOF structure with organic linkers that have particular chemical groups (such as carboxylate, hydroxyl, or amine groups) tailored to interact with specific uremic toxins. This localized functionalization enhances both the capacity and selectivity for different types of protein-bound toxins

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention optimizes parameters such as pore size, surface area, and chemical composition of the MOF materials to achieve rapid kinetics and high selectivity. By adjusting these parameters during synthesis, the adsorbents are tuned to specifically target uremic toxins with fast binding rates and high affinity

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If high-capacity adsorbents are used to remove uremic toxins, then the removal efficiency is improved, but the device complexity increases

Engineering Contradiction:

Improveuremic toxin removal efficiencyVSAvoidadsorbent system complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent develops universal MOF-based adsorbents that can remove multiple types of protein-bound uremic toxins (such as p-cresyl sulfate, indoxyl sulfate, and hippuric acid) through a single material system. This multi-functionality eliminates the need for multiple specialized adsorbents, thereby maintaining high removal efficiency while avoiding increased device complexity

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

MOFs achieve rapid and high-capacity removal of uremic toxins, exceeding 98% within minutes, with potential for multiple uses and recovery, effectively addressing the limitations of current therapies.

Implementation Method 1

MOFs with zirconium-based nodes and specific organic linkers, such as NU-1000, that facilitate π-π binding and electrostatic interactions for efficient adsorption of uremic toxins

Methodology Applied

Scientific Effectπ-π binding:

Implementation Method 2

PBTs bind to several adsorption sites on HSA by electrostatic interaction and/or van der Waals forces

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 3

These are mainly porous materials which can adsorb the uremic toxins into their pores

Methodology Applied

Scientific EffectAdsorption: Adsorption

Implementation Method 4

PBTs bind to several adsorption sites on HSA by electrostatic interaction and/or van der Waals forces

Methodology Applied

Scientific Effectvan der Waals force: Van der Waals Force

Data Source

PatentUS12403412B2Metal-organic frameworks for the removal of uremic toxins

Publication Date: 2025.09.02 NORTHWESTERN UNIV

AI summary

Metal-organic framework molecules with pyrene group-containing or biphenyl group-containing linkers for use in the removal of uremic toxins from biological samples that contain such toxins are provided. Also provided are methods for using the MOFs to remove uremic toxins from biological samples. The methods include hemodialysis of blood samples from patients suffering from a uremia-related disease, such as chronic kidney failure.