Library · Biology & lab methods

What Microfluidics & Lab-on-a-Chip got wrong, from 54 theses

Summary written by a model from the records below: These records document various technical failures, performance limitations, and trade-offs encountered across microfluidic and lab-on-a-chip platforms. Common issues include material incompatibilities such as PDMS swelling and adsorption, physical clogging or fouling, bubble entrapment, and droplet destabilization. These records come from graduate theses, 2021 to 2026, each labeled with its degree where the repository states it, and each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.

54
theses
16
institutions
56
failure records
7
failure modes

Plus 9 problems the authors left open, listed at the end.

Failure modes, by theses reporting them

Select a mode to jump to its records.

Droplet instability, coalescence, and poor encapsulation efficiency disrupt droplet microfluidics
11
11 theses · 6 institutions · 12 records
PDMS and elastomer materials suffer from solvent swelling, molecule adsorption, and fabrication defects
13
13 theses · 8 institutions · 13 records
Microchannels clog frequently due to particle sedimentation, high viscosity, and cellular fouling
10
10 theses · 7 institutions · 10 records
Uncontrolled bubble nucleation, gas permeability, and cavitation cause measurement and flow instability
7
7 theses · 4 institutions · 7 records
Cell shear stress, matrix contraction, and hydrogel detachment cause cell culture and organ-on-chip failure
4
4 theses · 3 institutions · 4 records
Microfluidic platforms perform worse than conventional bulk or benchtop baselines in throughput, purity, or yield
9
9 theses · 8 institutions · 9 records
Passive microchannel mixers provide insufficient mixing efficiency
1
1 theses · 1 institutions · 1 records

Droplet instability, coalescence, and poor encapsulation efficiency disrupt droplet microfluidics

11 theses · 6 institutions

Reagents such as IVTT mixtures and extraction lysis detergents destabilized emulsions and disrupted microfluidic droplet generation. In other cases, droplets adhered directly to electrodes, required heavy dilution to form stably, or suffered from evaporation and poor one-step amplification yields.

Tried and failed

undiluted isothermal amplification reaction encapsulation in droplet microfluidics applied to recombinase polymerase amplification mixture droplet generation. Outcome: unstable. Reason: droplets were unstable during microfluidic generation without significant aqueous dilution

Modular CRISPR-diagnostics for Infectious Diseases · MIT · PhD

Tried and failed

electrochemical manipulation of microdroplets over bare microelectrodes applied to droplet-based microfluidics. Outcome: unstable. Reason: droplets adhered directly to electrode surfaces without fluorinated thiol surfactant, permanently clogging the channel

Synthesis of model nanoparticle-peptide conjugates and development of an electrochemical strategy to regulate microdroplet pH in microfluidics · UT Austin · PhD

Tried and failed

microfluidic droplet generation without sample dilution applied to low-concentration protein solutions. Outcome: unstable. Reason: microchannel wettability issues caused droplet generation failure at low protein concentrations

Two-phase microfluidic approaches to study food protein functionality · Texas Tech · PhD

Tried and failed

direct ddPCR using commercial detergent lysis buffers applied to cell lysates for DNA quantification. Reason: detergents and harsh chemicals in extraction lysis buffers interfered with droplet formation

Investigating the heterogeneity of T Stem Cell Memory cell (Tscm) and their role in maintenance of long-term immunity following vaccination in humans · Imperial · PhD

Tried and failed

one-step direct in-droplet RT-PCR applied to single-cell transcript linkage. Outcome: worse than baseline. Reason: poor reaction efficiency and low yield compared to decoupled reverse transcription and amplification steps

Methods and Materials to Generate Antibody Repertoire Libraries · Harvard · PhD

Tried and failed

fluorosurfactant-stabilized microfluidic droplet pico-injection applied to cell-free protein synthesis reactions. Outcome: unstable. Reason: in vitro transcription-translation reaction components destabilized fluorosurfactant emulsions, causing severe droplet coalescence

Microdroplet assay development for metabolic engineering and synthetic biology applications · UT Austin · PhD

Tried and failed

microfluidic geometric constriction for droplet snap-off applied to oil trapping in microchannels. Reason: Pore throat dimensions exceeding critical aspect ratio failed to induce capillary instability required for spontaneous snap-off

Multiscale visualization of chemical enhanced oil recovery · UT Austin · PhD

Tried and failed

oscillatory microfluidic droplet transport at elevated temperatures applied to automated chemical reaction screening. Outcome: unstable. Reason: rapid solvent evaporation, droplet smearing, and condensation in unheated tubing outside the heated zone

Automating reaction development: hardware and software for fully-automated high-fidelity navigation of high-dimensional chemical reaction space · MIT · PhD

Lost to a baseline

Open microfluidic droplet volume monodispersity had a relative standard deviation of 5%–7%, whereas conventional closed-channel methods achieve 1%–3%.

Open microfluidic technologies for fundamental and applied studies of human health and the environment · University of Washington · PhD

Considered and rejected

Considered and rejected: Operating droplets in continuous oil media on the PurpleDrop board, rejected due to contamination, setup complexity, and failure to stop thermal evaporation during PCR.

Physical and Computational Approaches Towards More Scalable Molecular Systems · University of Washington · PhD

Considered and rejected

Considered and rejected: Simultaneous one-step in-droplet RT-PCR was abandoned due to low reaction yields and inefficiency in droplet linking.

Methods and Materials to Generate Antibody Repertoire Libraries · Harvard · PhD

Considered and rejected

Considered and rejected: Abandoned microfluidic water-in-oil droplet generation due to inconsistent droplet sizing, excessive sample waste during equilibration, and manual dispensing constraints.

Parallel synthesis and screening of optical probes for G-quadruplex DNA · Imperial · PhD

PDMS and elastomer materials suffer from solvent swelling, molecule adsorption, and fabrication defects

13 theses · 8 institutions

Microfluidic devices made of PDMS suffered from solvent absorption, organic solvent swelling, and non-specific adsorption of dyes and hydrophobic molecules. Devices also suffered from channel deformation under pressure, bonding leaks, and leaching of uncrosslinked oligomers that inhibited biological activity.

Tried and failed

fluorinated solvent microfluidic hydrodynamic focusing in PDMS applied to nanoparticle self-assembly. Reason: Solvent absorption into PDMS and wetting caused broad, polydisperse size distributions with large aggregates.

Developing artificial cells for delivering drug molecules to micro-engineered heart tissue · Imperial · PhD

Tried and failed

multitude interlayer bonding of PDMS microfluidics applied to microfluidic chromatin immunoprecipitation devices. Reason: improper interlayer bonding and sealing caused device fluid leaks

DEVELOPMENT AND EXPLORATION OF TECHNIQUES TO STUDY THE SPATIAL ORGANIZATION OF THE HUMAN GENOME · Cornell · PhD

Tried and failed

cell culture in unwashed PDMS microfluidic devices applied to bacterial spore germination. Outcome: no signal. Reason: Leaching of toxic uncrosslinked PDMS oligomers inhibited spore germination entirely without extensive solvent washing.

Microbes-on-a-chip: deciphering the responsiveness of microbes using microfluidic chemostats · Imperial · PhD

Tried and failed

Hydrogel membrane bonding without surface silanization applied to PDMS microfluidic devices. Outcome: unstable. Reason: Inconsistent membrane adhesion sensitive to water content and buffer composition.

Towards an artificial cell: Development of a system which self-regenerates the protein components of the PURE system in microfluidic reactors · EPFL · PhD

Tried and failed

3D-printed and milled molds for soft lithography applied to microfluidic channel fabrication. Reason: Molds produced via stereolithography, FDM, and CNC milling failed to yield functional PDMS channels

Investigating the role of shear stress, von Willebrand factor, platelets and neutrophils in the initiation of venous thrombosis · Imperial · PhD

Tried and failed

all-PDMS microfluidic channels under high operating pressure applied to intracellular delivery in microfluidic devices. Outcome: unstable. Reason: Severe channel deformation above 3 bar and delamination above 4 bar caused irreproducible processing

A biomechanics-based delivery strategy to primary immune cells for generating cell therapy with multiple gene knockout · Georgia Tech · PhD

Tried and failed

combinatorial fluorescent dye multiplexing in microfluidics applied to single cell optical barcoding. Outcome: unstable. Reason: Severe spectral shifts, non-specific PDMS adsorption, and intercellular cross-staining prevented reliable multiplexed decoding.

Development of high-throughput imaging-based single cell genotype-phenotype mapping platforms · Harvard · PhD

Considered and rejected

Considered and rejected: Rejected PDMS for microfluidic platform fabrication because of small molecule absorption and low throughput, opting for polystyrene injection molding and 3D DLP printed rigid resin.

Engineering Brain Tumor Microenvironment with Controlled Physical Features · Georgia Tech · PhD

Considered and rejected

Considered and rejected: Rejected using standard hydrocarbon-based organic solvents (toluene, chloroform, cyclohexane) in PDMS microfluidics due to PDMS swelling affecting channel width and surface treatments.

Microstructured Soft Materials · EPFL · PhD

Considered and rejected

Considered and rejected: Rejected PDMS-based microfluidics for final innervation platform due to small molecule absorption, laborious molding, and lack of open-top compound access.

Modelling Sensory Innervation of Cancer Using Organ-on-Chip Technology · Tübingen · PhD

Considered and rejected

Considered and rejected: Rejected PDMS for scalable/commercial microfluidic devices due to time-intensive processing, difficult sealing, swelling in non-polar organic solvents, and extraction of hydrophobic molecules

From Coulombic Materials to Fluids: Complex Behaviors in Physical Systems · Harvard · PhD

Considered and rejected

Considered and rejected: Rejected PDMS-based microfluidic chips in favor of borosilicate glass (Micronit) to prevent matrix swelling in the presence of light organic solvents.

Hydrocarbon gas injection for improving oil recovery in tight and shale oil reservoirs · UT Austin · PhD

Considered and rejected

Considered and rejected: Single-use PDMS-on-glass thin-section microfluidic chips rejected due to ~50% failure rate (glass cracking, leaking, Si background from PDMS, 1000x Si variance) in favor of a 304 stainless steel device

Kinetic analysis of leaching reactions in multi-component mineral systems · MIT · PhD

Microchannels clog frequently due to particle sedimentation, high viscosity, and cellular fouling

10 theses · 7 institutions

Narrow channels, dispensers, and tubing regularly clogged due to particle sedimentation, high sample viscosity in serum, and cell debris. Fluid currents, frozen droplets, and deformable nanovials also blocked microfluidic passages during operation.

Tried and failed

microfluidic device interaction assays applied to inter-organism microbial interactions. Outcome: unstable. Reason: unresolvable fluid currents caused severe channel clogging despite degassing and hydration modifications

Investigating the role of chemotaxis in the natural source zone depletion of petroleum hydrocarbons · Imperial · PhD

Tried and failed

continuous microfluidic particle delivery using syringe pumps applied to single-cell droplet encapsulation. Outcome: unstable. Reason: cell sedimentation and aggregation over extended runtimes altered the concentration reaching the microfluidic junction

Deep Learning with Computer Vision for Microfluidic Droplet and Cancer Detection · Texas Tech · PhD

Tried and failed

nanolitre dispensing with microfluidic dispenser applied to undiluted human serum. Outcome: unstable. Reason: high sample viscosity caused frequent needle and dispenser blockages

Evaluation and development of reference materials to support mass spectrometry imaging of endogenous metabolites in tissue · Imperial · PhD

Tried and failed

acoustic streaming microfluidic cell trapping applied to microfluidic cell sorting and collection. Reason: narrow channels clogged from vortex trapping, while wider channels severely reduced pumping efficiency

Development of soft microscopic implants and acoustically-powered machines for biomedical applications · EPFL · PhD

Considered and rejected

Considered and rejected: Rejected dropper-based droplet drying for traditional binder due to excessive viscosity clogging the dropper.

A Technical Study of Fish Collagen-Based Binder for Architectural Polychrome Painting in Jiangsu Province: History and Application · Penn · Master's

Considered and rejected

Considered and rejected: Rejected microfluidic droplet generation due to severe clogging, non-sterile workflows, low yield (4 h run yielded only 2 scaffolds), and sticky bead loss during pipetting.

Bioengineered scaffolds as a tool to decode the complexity of cancer cell interactions in vivo · Imperial · PhD

Considered and rejected

Considered and rejected: Rejected continuous emulsion flow PASST setup for sample collection due to persistent tubing clogging during in-line droplet freezing.

Porous ceramic frameworks for CO2 utilization · TU Wien · PhD

Considered and rejected

Considered and rejected: Rejected microfluidic droplet generation for sub-10 µm microparticles due to severe backpressure and high channel clogging risk.

Platelet-inspired microparticles for targeted drug delivery to the atherosclerotic plaque · Imperial · PhD

Considered and rejected

Considered and rejected: Rejected using 60 µm nanovials for droplet single-cell sequencing because they deformed in microfluidic channels and caused clogging; 35 µm nanovials were used instead.

Modeling the longevity and secretory capacity of engineered human plasma cells · University of Washington · PhD

Considered and rejected

Considered and rejected: Rejected 16-channel microfluidic flow chip with integrated inflow/outflow distributors due to biofilm clogging within distributor structures causing uneven flow.

Uncovering Transcriptional Heterogeneity during Vibrio cholerae Biofilm Development Aufdeckung der transkriptionellen Heterogenität während der Biofilmentwicklung von Vibrio cholerae · University of Marburg · PhD

Uncontrolled bubble nucleation, gas permeability, and cavitation cause measurement and flow instability

7 theses · 4 institutions

Gas permeability through elastomer membranes and Joule heating caused unintended bubble formation and electrical arcing during fluid flow. Trapped bubbles, nucleation at probe tips, and pressure-induced bubbling introduced severe measurement artifacts and disrupted cellular gradients.

Tried and failed

microfluidic morphogen gradient patterning applied to elongated embryonic stem cell organoids. Reason: air bubble entrapment in the microfluidic chamber caused tissue fragmentation and disrupted morphogen gradient exposure

Materials and morphogen gradients-guided brain organoid anteroposterior polarization study · Imperial · Master's

Tried and failed

pneumatic actuation of elastomer membranes applied to microfluidic flow resistance control. Reason: gas permeability of the elastomer membrane under pressure caused bubble formation in the fluid channels

Lab-on-a-chip and numerical tools for a better understanding and prediction of chemokine gradients · Imperial · PhD

Tried and failed

passive microcavity arrays for bubble trapping applied to in situ microfluidic optical spectroscopy. Outcome: unstable. Reason: cylindrical indents lacked reproducibility for trapping stable air bubbles without manual injection

Studying secondary structural changes and aggregation in monoclonal antibodies using ATR-FTIR spectroscopic imaging · Imperial · PhD

Tried and failed

active flow microfluidics over microwell arrays applied to trapped 3D cell spheroids. Outcome: unstable. Reason: fluid flow introduced air bubbles, dislodged aggregates, and caused shear-induced sample dissociation

Label-free plasmonic microarray for multiplexed analysis of cells and tumor organoids · EPFL · PhD

Tried and failed

low-flow continuous microfluidic electroporation applied to bacterial cell transformation. Outcome: unstable. Reason: Joule heating caused bubble formation and electrical arcing at low flow rates

Novel High-throughput Technologies for Applications in Microbiology · MIT · PhD

Tried and failed

QCM-D characterisation of surface functionalisation applied to conjugated polymer thin films. Outcome: unstable. Reason: Polymer swelling in organic solvent, film delamination from sensor substrates, and microfluidic bubble formation

Functionalised organic field-effect transistors as biosensors for circulating-tumour DNA detection · Imperial · PhD

Considered and rejected

Considered and rejected: Rejected continuous plunging water jets in favor of an intermittent plunging sheet because continuous bubbling prevents fine bubbles from evolving/bursting freely, biasing droplet size distributions.

Spray Aerosols From Saltwater to Freshwater Breaking Waves · Virginia Tech · Doctorate

Cell shear stress, matrix contraction, and hydrogel detachment cause cell culture and organ-on-chip failure

4 theses · 3 institutions

Peristaltic pumping shear oscillations and active flow caused cell detachment, aggregate dislodgement, and chip failure. Hydrogels frequently detached from open-bottom microchannels or contracted excessively beyond quality control thresholds, disrupting vascular and 3D culture models.

Tried and failed

microfluidic cell monolayer culture under shear stress applied to ovarian cancer cell lines. Outcome: unstable. Reason: cells failed to form stable adherent monolayers and detached under minimal shear during media exchange

Shear stress in microfluidics: avidity-based selection of T cell and natural killer cells & mechanical activation of pancreatic stellate cells · Imperial · PhD

Tried and failed

commercial microfluidic devices with open bottom channels applied to 3D cell invasion assays in hydrogels. Reason: Hydrogel detached and cells migrated along the 2D plastic surface rather than invading the 3D matrix

IN VITRO MODELING AND ANALYSIS TO INVESTIGATE THE METABOLIC REGULATION OF BREAST CANCER INVASION TOWARDS THE VASCULATURE · Cornell · PhD

Tried and failed

synthetic poly(ethylene glycol) hydrogel encapsulation in microfluidics applied to bone marrow organ-on-a-chip vascularization. Reason: Rapid gelling caused channel leakage, bubbling, defective vascular network self-assembly, and aberrant stromal marker expression.

Engineered Systems of the Germinal Center and Bone Marrow for Antigen-Specific B Cell Generation and Longevity · Georgia Tech · PhD

Tried and failed

peristaltic pump driven microfluidic perfusion applied to endothelial cell culture under shear. Outcome: unstable. Reason: excessive pressure swings and shear oscillations broke chips and killed cells

Investigating the role of shear stress, von Willebrand factor, platelets and neutrophils in the initiation of venous thrombosis · Imperial · PhD

Microfluidic platforms perform worse than conventional bulk or benchtop baselines in throughput, purity, or yield

9 theses · 8 institutions

Several microfluidic approaches exhibited lower sorting purity than FACS, lower throughput than bulk or commercial systems, and lower nanoparticle batch yields than benchtop tanks. Other microfluidic setups required more amplification cycles or had lower diagnostic accuracy than standard smears and assays.

Lost to a baseline

Droplet microfluidics assay yielded poorer diagnostic accuracy and correlation than standard Giemsa thick blood smear microscopy and HRP-2 RDTs

Technology transfer and assay optimisation of the droplet microfluidic assay for malaria diagnostics in human saliva - A pilot study in Gabon · Tübingen · PhD

Lost to a baseline

Convective microfluidic transfection of large multicistronic CRISPR/Cas9 plasmids into iPSCs performed no better than standard Lipofectamine Stem (<1% efficiency).

Microfluidic Cell Processing for Personalized and Regenerative Medicine · Georgia Tech · PhD

Lost to a baseline

Microfluidic cell sorting protocols do not yet reach the purity levels of fluorescence-activated cell sorting (FACS)

Profiling, prototyping, and perturbing human immune responses · MIT · PhD

Lost to a baseline

DisCo throughput (maximally 300-350 cells/hour) is lower than stochastic droplet microfluidics platforms (e.g., standard Drop-seq, 10X Chromium) due to valve actuation latency.

Developing new tools to study and program cell fate at the single-cell level · EPFL · PhD

Lost to a baseline

Microfluidic selection produced significantly lower sperm concentration (70.93 x 10^6/mL) than unprocessed control (350.05 x 10^6/mL) and colloidal centrifugation (266.39 x 10^6/mL).

OPTIMIZING SPERM SELECTION: EFFECTS OF MICROFLUIDIC AND COLLOIDAL CENTRIFUGATION PROCESSING ON DNA FRAGMENTATION IN FROZEN-THAWED STALLION SPERM · Sam Houston State University · Master's

Lost to a baseline

Droplet tagmentation using non-dissolvable hydrogels required 1-2 additional qPCR amplification cycles compared to bulk control tagmentation.

Integrated Analysis of Single-Cell Atlases and Droplet Microfluidics Based Single-Cell Sequencing Methods · Harvard · PhD

Tried and failed

PDMS-on-glass microfluidic constriction electrodes applied to single-cell impedance cytometry and electroporation. Outcome: worse than baseline. Reason: exhibited significantly worse signal-to-noise ratio and electroporation performance compared to PCB through-hole design

Single-Cell Impedance Cytometry for the Control of Single-Cell Electroporation in a Flow-Through Device · Georgia Tech · PhD

Lost to a baseline

Benchtop tank reactor synthesis produces larger batch volumes of nanoparticles than microfluidic reactor synthesis despite lower reproducibility.

Complex Nanostructures and Bio-Nanoscale Interactions: Well Defined Synthesis, Identification and Biological Effects · University College Dublin · PhD

Lost to a baseline

Capillary-driven microfluidic assays showed slightly lower sensitivity curve slope than standard ELISA due to spontaneous target dilution and ultra-short incubation times.

Capillary-driven Microfluidic Biosensing Platforms for Digital Biomolecule Detection · Texas Tech · PhD

Passive microchannel mixers provide insufficient mixing efficiency

1 theses · 1 institutions

Linear channel passive micromixers lacked adequate chaotic advection and contact area compared to obstacle-based designs. Y-mixers and opposed T-mixers also failed to generate sufficient mixing efficiency for continuous flow nanoparticle synthesis.

Tried and failed

Linear channel passive micromixer applied to Microfluidic stream mixing. Outcome: worse than baseline. Reason: Insufficient chaotic advection and contact area compared to obstacle-based designs

Multimodal Electronic Cell Phenotyping via Multiplexed Impedance Sensors · Georgia Tech · PhD

Left open by the authors

Problems the authors named and did not get to.

Left open

Design and validate primer pools to generate linked sequencing libraries for heterodimeric molecules such as T-cell receptors using droplet microfluidics. Blocker: Requires wet lab access, microfluidic apparatus, biological samples, and reagent synthesis

Methods and Materials to Generate Antibody Repertoire Libraries · Harvard · PhD

Left open

Optimize workflow for digital droplet or digital partitioning PCR systems to assess inhibitor susceptibility compared to RT-qPCR in wastewater surveillance. Blocker: Requires wet lab facilities, wastewater samples, and digital PCR apparatus/reagents.

Wastewater Surveillance for Emerging Infectious Diseases: Optimization and Implementation of Methods · University of Washington · PhD

Left open

Design and fabricate microfluidic transistor circuits for multi-particle co-encapsulation and droplet pairing in single-cell sequencing. Blocker: Requires a microfluidics wet lab and physical fabrication facilities for testing flexible membrane fluidic circuits

Microfluidic Transistors for the Control of Liquids and Particles · Harvard · PhD

Left open

Adopt digital droplet PCR (ddPCR) to quantify low-abundance cell-free RNA transcripts and reduce stochastic variability. Blocker: Requires a wet lab, biological samples (serum/CSF), and digital droplet PCR (ddPCR) instrumentation.

Evaluation of Cell-Free RNA as Minimally Invasive Biomarkers of Target Engagement · Harvard · Master's

Left open

Incorporate barcoding schemes into the droplet microfluidic viral recovery workflow to enable multiplexed detection and sequencing of multiple viruses. Blocker: Requires a wet lab, microfluidic droplet generation and sorting apparatus, and biological reagents.

Single-Virus/Single-Cell Sequencing with Droplet Microfluidics · Harvard · PhD

Left open

Develop a continuous flow droplet reactor in tubing to scale up nanoparticle synthesis and improve batch reproducibility. Blocker: Requires a physical chemistry/materials wet lab and specialized microfluidic or flow chemistry hardware

HYBRIDIZED NANOSCALE TRANSITION METAL OXIDES AS ANODE MATERIALS FOR LITHIUM-ION BATTERIES · Georgia Tech · PhD

Left open

Optimize droplet microfluidic sorting and amplification protocols to prevent proviral DNA fragmentation and improve post-sort retrieval for full-length single-genome amplification. Blocker: Requires wet-lab facilities, microfluidic cell sorters (Sony MA900), and biological reagents to handle and amplify proviral DNA.

The impact of HIV specific broadly neutralising antibodies on mucosal immunity and the HIV reservoir · Imperial · PhD

Left open

Incorporate hydrogel particle-templated droplets or on-bead rolling circle amplification chemistries into the droplet digital extracellular vesicle analysis platform. Blocker: Requires a wet lab, microfluidic devices, chemical reagents, and physical extracellular vesicle samples

High Throughput Immunospecific Detection And Analysis On Subcellular Nanomaterials At Single Particle Level · Penn · PhD

Left open

Develop microdroplet applications that mimic fed-batch fermentations to improve translation into benchtop bioreactors. Blocker: Requires a wet lab, microfluidic devices, and biological fermentation setups.

Microdroplet assay development for metabolic engineering and synthetic biology applications · UT Austin · PhD

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