Conductive metal-organic frameworks based sensors for disease diagnosis

Frames early diagnosis, biomarker sensing and the shortcomings of conventional assays and insulating MOFs; positions c-MOFs as porous conductive sensor materials.

Relevance: Core · 1 · Introduction

Reviews c-MOF sensor examples across exhaled breath, blood, sweat and other biofluids, emphasising mechanisms and representative analytical performance.

Relevance: Supporting · 2 · Application of c-MOFs-based sensors in biological samples · Table 1

Synthesises the review's challenges: limited structural diversity, insufficient stability, single-analyte emphasis, matrix interference, poor wearable adhesion, biofouling and inadequate clinical validation.

Relevance: Core · 4 · Conclusion and prospect

Defines c-MOFs, gives early historical milestones, and links pi-conjugated ligand chemistry to processable films and practical sensing devices.

Relevance: Core · 1 · Conductive metal-organic frameworks · Figure 1

Collects figure-only transport schematics, structural design examples, biological sensing mechanisms and a representative application table with analytes, real samples, ranges and LODs.

Relevance: Core · 9 · Figures and tables · Table 1

Connects high conductivity, surface area and structural designability to signal amplification, active-site exposure, diffusion, selectivity and response kinetics.

Relevance: Core · 2 · Structural designability · Figures 3-4

Organises conductivity through carrier density and mobility, then classifies charge transport into physical and chemical modes with band, hopping, through-bond, through-space, redox-hopping and guest-promoted pathways.

Relevance: Core · 1 · Mechanism of electron conduction · Figure 2

Biological sample classes

Applications are organised by biofluid or breath matrix, making the review useful for separating non-invasive, minimally invasive and invasive diagnostic contexts.

Categories: exhaled breath · blood · sweat · urine · cerebrospinal fluid

2 · Application of c-MOFs-based sensors in biological samples · Table 1

Sensor-enabling c-MOF properties

The property section organises c-MOF advantages around fast charge transduction, accessible active sites and tunable electronic or interfacial chemistry.

Categories: high electrical conductivity · high specific surface area · structural designability

1-2 · Property

Sensing signal modalities

The application section spans several device transduction modes; this is useful for Chapter 1 when separating intrinsic transport from sensor readout architecture.

Categories: chemiresistive sensing · photoelectrochemical sensing · field-effect transistor sensing · electrochemical impedance or voltammetric sensing · electrochemiluminescence

2-4 · Application of c-MOFs-based sensors in biological samples · Figures 5-8

Structural design levers

The review illustrates how metal identity, ligand geometry, topology, defects and composites tune binding affinity, diffusion, conductivity and response kinetics.

Categories: metal-node modulation · ligand insertion · topological tuning · missing-linker or defect engineering · hybridisation with conductive or catalytic additives

2 · Structural designability · Figure 4

Charge-transport mechanism classes

The review presents a transport taxonomy in which conductivity is governed by carrier density and mobility, with MOF charge transport classified into physical and chemical modes and expanded by redox or guest-mediated pathways.

Categories: physical modes: band theory · physical modes: hopping theory · chemical modes: through-bond · chemical modes: through-space · redox hopping · guest-promoted transport

1 · Mechanism of electron conduction · Figure 2

Biofabric-supported ionic c-MOF films based on Zn-TCPP used for room-temperature breath ammonia sensing.

Conduction: NH3 chemisorption at open Zn sites increases mobile ion carriers and decreases resistance.

Representative materials: Zn-TCPP-6 · IC-MOF Zn-TCPP

Nodes / linkers: Zn · TCPP porphyrin

2 · Exhaled breath · Figure 5d-e

Conductive frameworks where enlarged macrocyclic or extended pi-conjugated linkers increase surface area and pore aperture.

Conduction: High porosity is paired with intrinsic conductivity to improve adsorption, diffusion and chemiresistive response.

Representative materials: Cu-HHTC · HIOTP-Ni · HIOTP-Cu

Nodes / linkers: Cu · Ni · HHTC · HAOTP-derived HIOTP

2 · High specific surface area · Figure 3

Two-dimensional pi-conjugated frameworks built from triphenylene-derived linkers and transition-metal nodes, often discussed as graphenelike conductive MOFs.

Conduction: In-plane pi-d conjugation and dense interlayer pi-pi stacking provide delocalised or semiconducting pathways and support electrochemical, ECL and FET sensors.

Representative materials: Ni3(HITP)2 · Ni3(HHTP)2 · Cu3(HHTP)2 · CuxNi3-x(HHTP)2 · Zn-HHTP

Nodes / linkers: Ni · Cu · Zn · Co · hexahydroxytriphenylene · hexaiminotriphenylene · related HXTP ligands

1 · Mechanism of electron conduction · Figure 1

Isostructural Cu and Ni frameworks used by the review to isolate the effect of metal-node chemistry on NO binding and charge transfer.

Conduction: Cu sites provide stronger NO coordination and charge transfer than Ni sites, producing sharply different chemiresistive responses despite structural similarity.

Representative materials: Cu3(HIB)2 · Ni3(HIB)2

Nodes / linkers: Cu · Ni · HIB

2 · Structural designability · Figure 4a

Cu-HHTP-derived frameworks where DHBQ insertion expands pore size without enlarging the core ligand.

Conduction: Ligand insertion is presented as a way to preserve conjugated pathways while increasing pore size and analyte diffusion.

Representative materials: Cu3(HHTP)(DHBQ)1.5

Nodes / linkers: Cu · HHTP · DHBQ

2 · Structural designability · Figure 4b

Template-assisted heterostructures that combine a porous MOF template with a conductive MOF network.

Conduction: The review attributes sensing to conductive Ni3(HITP)2 networks, NUS-8 adsorption sites, interfacial electronic coupling and oriented thin-film diffusion channels.

Representative materials: Ni3(HITP)2/NUS-8

Nodes / linkers: Ni · HITP · NUS-8 template chemistry

2-3 · Exhaled breath · Figure 5f-h

Conductive tetrathiafulvalene frameworks immobilising radical cations to create a spin-mediated chemiresistive pathway for NO detection.

Conduction: Ligand spin immobilisation adds spin-spin exchange with NO and increases conductivity relative to non-oxidised M-TTF.

Representative materials: Co-TTF-spin MOF · Zn-TTF-spin MOF · Cd-TTF-spin MOF

Nodes / linkers: Co · Zn · Cd · TTF radical cation

3 · Exhaled breath · Figure 5j-k

Conductive MOF electrodes whose surface hydrophilicity is tuned to reduce lipid fouling during sweat monitoring.

Conduction: High porosity and catalytic activity are coupled with hydration-layer-mediated antifouling or wet-adhesive electrode architectures.

Representative materials: Cu-HHTP · Ni3HHTP2 wearable membrane electrodes

Nodes / linkers: Cu · Ni · HHTP

4 · Sweat · Figure 7

Hybridisation with conductive, catalytic or antifouling components

Combine c-MOFs with graphene, nanoparticles, polymers, enzymes, luminescent complexes, biofabrics or hydrophilic electrode surfaces to enhance transduction and practical device performance.

Claimed effects: The review links hybridisation to improved charge transfer, catalytic activity, ECL signal, stability, fouling resistance and wearable operation.

Controlling variables: hybrid component · interface quality · charge-transfer coupling · biofouling resistance · substrate compatibility

Representative materials: Au@Co3O4NPs/NiCo(HITP) · Ru@Ni3(HITP)2 · GOx@Zn-HHTP · Cu-HHTP wearable patch

Caveat: Hybrid systems may make it harder to attribute performance to intrinsic c-MOF transport alone.

5 · Conclusion and prospect

Interfacial and in situ growth for device films

Use interfacial growth, layer-by-layer epitaxy or in situ synthesis to produce oriented or substrate-integrated c-MOF films for sensors.

Claimed effects: Improves film quality, active-site exposure, mechanical integration and access to wearable or portable device formats.

Controlling variables: substrate · growth interface · film orientation · layer-by-layer cycles

Representative materials: LR-epi-MOF · Zn-TCPP-6 · Ni3(HHTP)2 FET films

Caveat: The review later cautions that adhesion to flexible substrates and reproducible film thickness remain unresolved.

1 · Conductive metal-organic frameworks

Ligand insertion to enlarge pores

Insert a bridging ligand between HHTP and Cu nodes to expand pores while retaining a conjugated 2D framework.

Claimed effects: Larger pores accelerate analyte diffusion and improve electrochemical sensing of AA and UA.

Controlling variables: inserted ligand length · bridging architecture · pore aperture · coordination geometry

Representative materials: Cu3(HHTP)(DHBQ)1.5

Caveat: The review gives a concept-level design rule and selected performance, not a universal pore-size optimum.

2 · Structural designability · Figure 4b

Metal-node modulation

Change metal nodes in isostructural c-MOFs to alter analyte binding affinity, orbital matching and charge-transfer efficiency.

Claimed effects: Can dramatically enhance selectivity and sensitivity when the analyte coordinates selectively to one metal node.

Controlling variables: metal identity · d-orbital occupancy · local coordination site · framework topology preservation

Representative materials: Cu3(HIB)2 · Ni3(HIB)2

Caveat: The evidence is presented as a specific NO case; it should not be generalised to all gases without primary validation.

2 · Structural designability · Figure 4a

Missing-linker defect engineering

Introduce defect sites through partially oxidised HAB ligands to expose hydroxyl sites and tune surface reactivity.

Claimed effects: Defects reduce adsorption/desorption barriers and improve fast reversible humidity sensing.

Controlling variables: ligand oxidation state · defect density · hydroxyl site availability · amorphous versus crystalline structure

Representative materials: aNi-HAB

Caveat: The example targets humidity rather than a disease biomarker, so it is most useful as a structure-property analogue.

2 · Structural designability · Figure 4d

Topological tuning by solvent and deprotonation control

Control deprotonation and coordination geometry to access 1D, 2D sql and 2D kgm topologies with different conductivity and gas response.

Claimed effects: The review reports five-order conductivity modulation and NH3-responsive chemiresistive behaviour.

Controlling variables: solvent conditions · ligand deprotonation · coordination geometry · network topology

Representative materials: 1D Cu-MOF-1 · 2D sql-Cu-MOF-2 · 2D kgm-Cu-MOF-3

Caveat: Conductivity depends on pellet versus thin-film form, so device-processing context matters.

2 · Structural designability · Figure 4c

Most disease-diagnosis studies remain in standard samples or simulated environments, with limited validation using patient breath, blood or other clinical samples.

Proposed direction: Conduct systematic clinical-sample validation of stability, specificity and reproducibility before translational claims.

5 · Conclusion and prospect

Some c-MOF variants still lag behind graphene and carbon nanotubes, which may impair charge transport and sensing response.

Proposed direction: Improve intrinsic conductivity through ligand, node, topology and hybridisation strategies without sacrificing porosity.

5 · Conclusion and prospect

Structurally analogous interferents in real biofluids compromise selectivity.

Proposed direction: Evaluate selectivity in realistic biological matrices and integrate antifouling or selective-recognition layers without blocking charge transport.

5 · Conclusion and prospect

Many diseases lack a single specific biomarker, but most c-MOF sensors target a single or limited set of analytes.

Proposed direction: Develop multi-channel or array-type c-MOF sensor systems with data-driven models for biomarker panels.

5 · Conclusion and prospect

Crystal size, defect density and film thickness variations undermine reproducible sensor performance.

Proposed direction: Develop controllable, large-area fabrication routes such as gas-liquid interface synthesis, in situ growth and 3D printing.

5 · Conclusion and prospect

c-MOF frameworks may collapse or degrade under strongly acidic/basic, high-temperature or high-humidity physiological environments.

Proposed direction: Engineer long-term chemical stability alongside high conductivity, including hybrid frameworks and stability-oriented linker/node selection.

5 · Conclusion and prospect

Reported c-MOF structures are relatively limited and rely heavily on a few classical ligands and common transition metals.

Proposed direction: Use rational and computational design to develop new architectures with higher conductivity, stability and tunable active sites.

5 · Conclusion and prospect

Weak adhesion between c-MOF films and flexible substrates can cause detachment or increased contact resistance during movement and sweat fluctuation.

Proposed direction: Improve film-substrate integration, wet adhesion and mechanical durability on PET, PDMS, textiles and skin-adherent platforms.

5 · Conclusion and prospect