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 "title": "Open flow microperfusion",
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 "excerpt": "Open flow microperfusion (OFM) is a minimally invasive method that continuously collects unfiltered interstitial fluid from tissue through a membrane-free catheter, measuring drugs, metabolites, and proteins over time.",
 "snippet": "Open flow microperfusion (OFM) is a minimally invasive method that continuously collects unfiltered interstitial fluid from tissue through a membrane-free catheter, measuring drugs, metabolites, and proteins over time.",
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 "markdown": "# Open flow microperfusion\n\nOpen flow microperfusion (OFM) is a minimally invasive sampling method that continuously collects unfiltered, merely diluted interstitial fluid (ISF) from living tissue through a thin, membrane-free perfused catheter, allowing local concentrations of drugs, metabolites, and proteins to be measured over time.<sup>[1](https://www.joanneum.at/ofm/ofm-technology/)</sup> Unlike microdialysis, which filters the fluid through a dialysis membrane, OFM exposes the perfusate directly to the tissue through macroscopic openings, so the sample keeps the solutes the membrane would otherwise exclude, including proteins and protein-bound drug.<sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0165027018302917)</sup> It is used in metabolic monitoring, dermal pharmacokinetics, and brain drug-transport studies.\n\n| Key fact | Detail |\n|---|---|\n| Sample type | Diluted but unfiltered ISF; no dialysis membrane, no molecular-weight cutoff<sup>[1](https://www.joanneum.at/ofm/ofm-technology/)</sup> |\n| Flow rates | 0.1 to 10 µL/min<sup>[1](https://www.joanneum.at/ofm/ofm-technology/)</sup> |\n| Typical dermal protocol | 1 µL/min nominal flow, ~60 µL ISF per hour per probe<sup>[3](https://link.springer.com/article/10.1007/s11095-023-03645-3)</sup> |\n| Wear duration | Up to 25 h of continuous dermal sampling in clinical studies<sup>[4](https://onlinelibrary.wiley.com/doi/10.1111/srt.12071)</sup> |\n| Probe types | Linear probes for skin and upper subcutis (dOFM, aOFM); concentric probes for deep subcutis, muscle, organs, and brain (cOFM)<sup>[1](https://www.joanneum.at/ofm/ofm-technology/)</sup> |\n| Calibration | Zero flow, no net flux, recirculation, endogenous, and ionic reference techniques<sup>[5](https://tugraz.elsevierpure.com/en/publications/monitoring-of-biofluids-in-microsamples-investigations-for-glucos/)</sup> |\n| Protein access | Samples ISF including proteins, where microdialysis measures only unbound drug<sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0165027018302917)</sup> |\n\n## How it works\n\nOFM is based on a double-lumen catheter with macroscopic perforations inserted into tissue and constantly perfused.<sup>[5](https://tugraz.elsevierpure.com/en/publications/monitoring-of-biofluids-in-microsamples-investigations-for-glucos/)</sup> The perfusate flows down the inner lumen, equilibrates partially with the surrounding ISF through the open exchange area, and is collected through the outer lumen.<sup>[6](https://pubmed.ncbi.nlm.nih.gov/9203447/)</sup> Because the exchange surface is open rather than a dialysis membrane, there is no molecular-weight cutoff: the direct liquid pathway between perfusate and ISF provides an unfiltered, diluted ISF sample, with analyte-specific partial equilibration affecting measured concentrations.<sup>[1](https://www.joanneum.at/ofm/ofm-technology/)</sup>\n\nThe degree of equilibration is expressed as relative recovery (RR), the fraction of the tissue concentration that appears in the sample. RR depends on the analyte's diffusivity in ISF, the probe's total exchange area, and the perfusion flow rate.<sup>[3](https://link.springer.com/article/10.1007/s11095-023-03645-3)</sup> The chemically inert, smooth probe surface minimizes adsorptive analyte loss, and cOFM samples ISF that includes proteins, whereas microdialysis sampling only allows measurement of unbound drug concentrations.<sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0165027018302917)</sup>\n\n## How it is done\n\nA typical dermal study illustrates the workflow. Linear dOFM probes are inserted intradermally through 20G hollow needles, and the correct insertion depth is verified with 22 MHz ultrasound.<sup>[3](https://link.springer.com/article/10.1007/s11095-023-03645-3)</sup> The CE-certified dOFM probe DEA15003 is a highly flexible linear probe with a demarcated 15-mm fully permeable section, 0.5 mm outer diameter, inserted over 30 mm through a standard 0.9-mm hollow needle.<sup>[7](https://link.springer.com/article/10.1007/s40262-016-0442-z)</sup>\n\nPerfusate and flow are chosen to match the tissue and analyte. Clinical dOFM perfusion fluid (ELO-MEL isotone) with 2% human serum albumin has been used in preclinical dermal work, with materials qualified in vitro to exclude non-specific adsorption of the study drugs.<sup>[3](https://link.springer.com/article/10.1007/s11095-023-03645-3)</sup> A topical bioequivalence study used sterile perfusate containing 1% albumin and 600 mg/dL glucose.<sup>[7](https://link.springer.com/article/10.1007/s40262-016-0442-z)</sup> Sampling is initiated by flushing the probes for 5 min at 10 µL/min, then reducing flow to the nominal 1 µL/min, delivering about 60 µL of dermal ISF per hour; fractions are collected hourly, in one study from −1 h to 36 h post-dose with twelve probes per subject.<sup>[3](https://link.springer.com/article/10.1007/s11095-023-03645-3)</sup><sup> • </sup><sup>[7](https://link.springer.com/article/10.1007/s40262-016-0442-z)</sup> Operating flow rates across the technology range from 0.1 to 10 µL/min.<sup>[1](https://www.joanneum.at/ofm/ofm-technology/)</sup>\n\nRecovery is calibrated by several established procedures: the zero flow rate and no net flux protocols, and the recirculation, endogenous, and ionic reference techniques.<sup>[5](https://tugraz.elsevierpure.com/en/publications/monitoring-of-biofluids-in-microsamples-investigations-for-glucos/)</sup> In an early adipose study, recovery was monitored continuously as the ratio of sampled-fluid conductivity to subcutaneous tissue-fluid conductivity, assumed to be 1.28 S/m at 25 °C.<sup>[6](https://pubmed.ncbi.nlm.nih.gov/9203447/)</sup> For protein-bound drugs, empirical values of \\( \\mathrm{RR}_{\\mathrm{u}} = 40\\% \\) for the unbound fraction and \\( \\mathrm{RR}_{\\mathrm{b}} = 10\\% \\) for the protein-bound fraction have been combined as \\( \\mathrm{RR}_{\\mathrm{tot}} = \\mathrm{RR}_{\\mathrm{u}} \\cdot f_{\\mathrm{u}} + \\mathrm{RR}_{\\mathrm{b}} \\cdot f_{\\mathrm{b}} \\).<sup>[3](https://link.springer.com/article/10.1007/s11095-023-03645-3)</sup> A zero flow rate experiment in cerebral work ran for 24 h.<sup>[8](https://mdpi-res.com/d_attachment/pharmaceutics/pharmaceutics-15-01880/article_deploy/pharmaceutics-15-01880.pdf?version=1688451037)</sup>\n\n## Origin\n\nThe published clinical record begins with on-line glucose monitoring in subcutaneous adipose tissue of healthy volunteers, using a double-lumen catheter, an isotonic ion-free perfusate, and an extracorporeal sensor cell during hyperglycemic glucose loads (n=8), a hypoglycemic hyperinsulinemic clamp (n=6), and 24-h monitoring (n=7).<sup>[6](https://pubmed.ncbi.nlm.nih.gov/9203447/)</sup> In that study, fasting subcutaneous glucose was 94% of arterialized venous plasma glucose.<sup>[6](https://pubmed.ncbi.nlm.nih.gov/9203447/)</sup> A follow-up validation study showed adipose ISF glucose lower than venous plasma at basal steady state and during hyperglycemic clamp.<sup>[9](https://pubmed.ncbi.nlm.nih.gov/9950802/)</sup>\n\nThe technology includes membrane-free probe platforms, including dermal OFM devices that became CE-certified medical devices described as safe, tolerable, precise, and versatile in clinical research.<sup>[1](https://www.joanneum.at/ofm/ofm-technology/)</sup><sup> • </sup><sup>[10](https://tugraz.elsevierpure.com/en/publications/dermal-open-flow-microperfusion-dofm-design-evaluation-research/)</sup>\n\n## Variants\n\nTwo probe geometries cover most uses. Linear OFM probes are designed for skin (dOFM) and the upper layers of subcutaneous tissue (aOFM); concentric OFM probes are designed for deeper tissue regions such as deep subcutis, muscle, organs, or the brain (cOFM), and both types come in different shaft lengths and open exchange areas.<sup>[1](https://www.joanneum.at/ofm/ofm-technology/)</sup> In a clinical applicability evaluation, physicians inserted 141 membrane-free dOFM probes into the dermis of 17 healthy and psoriatic volunteers and sampled dermal ISF for 25 h using wearable devices.<sup>[4](https://onlinelibrary.wiley.com/doi/10.1111/srt.12071)</sup>\n\nFor cerebral work, a step-by-step cOFM protocol exists for pharmacokinetic and pharmacodynamic studies in mouse or rat brain with an intact blood-brain barrier.<sup>[11](https://currentprotocols.onlinelibrary.wiley.com/doi/10.1002/cpph.60)</sup> The membrane-free cOFM probe body construct itself contains the open exchange area, and a 14-day recovery period after probe implantation is recommended before initiating sampling to ensure blood-brain barrier integrity.<sup>[12](https://mdpi-res.com/d_attachment/pharmaceutics/pharmaceutics-14-01051/article_deploy/pharmaceutics-14-01051.pdf?version=1652424551)</sup> In rats, BBB disruption caused by cOFM probe implantation in the frontal cortex heals within 15 days.<sup>[13](https://journals.plos.org/plosone/article/file?id=10.1371%2Fjournal.pone.0098143&type=printable)</sup>\n\nTwo advanced variants extend OFM to absolute quantification. OFM-recirculation and OFM-suction yielded absolute subcutaneous ISF albumin concentrations of 11.2 mg/ml and 14.2 mg/ml in pigs, with ISF-to-plasma ratios of 0.39 ± 0.04 and 0.47 ± 0.1 after 20 recirculation cycles.<sup>[14](https://iopscience.iop.org/article/10.1088/2057-1976/abc3a7)</sup>\n\n## Applications\n\nMetabolic monitoring was the first application, with continuous on-line adipose glucose measurement during clamps and 24-h monitoring.<sup>[6](https://pubmed.ncbi.nlm.nih.gov/9203447/)</sup> Dermal pharmacokinetics is a major clinical use: dOFM supports topical bioequivalence assessment, with intradermal probes sampling dermal ISF continuously around a dosing period.<sup>[7](https://link.springer.com/article/10.1007/s40262-016-0442-z)</sup> In oncology, a cOFM platform coupled to HILIC-HRMS monitored the glioblastoma tumor microenvironment metabolome in brain ISF in vivo, finding 281 metabolites of adequate analytical quality in brain ISF, with over 30% of the metabolome altered in tumors compared to controls (p < 0.05).<sup>[15](https://www.sciencedirect.com/science/article/pii/S000326702500577X)</sup> Membrane-free cOFM probes also allowed prolonged sampling of the therapeutic antibody ocrelizumab in mouse brain ISF with simultaneous BBB integrity monitoring.<sup>[8](https://mdpi-res.com/d_attachment/pharmaceutics/pharmaceutics-15-01880/article_deploy/pharmaceutics-15-01880.pdf?version=1688451037)</sup> For large-molecule development, monoclonal antibody formulations were slowly infused via minimally invasive OFM probes into porcine subcutaneous tissue to minimize injection-site depot formation, with ISF sampled hourly using the same probes, as a model to predict human subcutaneous mAb bioavailability.<sup>[16](https://lirias.kuleuven.be/4279542)</sup>\n\n## Limitations and alternatives\n\nThe main documented failure mode is tissue trauma from probe implantation, which can elevate protein concentrations in samples; bleeding during experiments, particularly at the beginning of OFM-suction experiments and during the first few hours of sampling, can contaminate samples, so analysis was restricted to samples collected after bleeding ceased, and probes were pre-perfused for 5 min with ELO-MEL isotone to clear blood from the lumen.<sup>[14](https://iopscience.iop.org/article/10.1088/2057-1976/abc3a7)</sup>\n\nCompared with microdialysis, OFM trades the membrane's molecular-weight cutoff for direct access to proteins and protein-bound drug; microdialysis membranes exclude the majority of proteins, so most drug-protein interactions cannot be investigated with microdialysis.<sup>[2](https://www.sciencedirect.com/science/article/abs/pii/S0165027018302917)</sup><sup> • </sup><sup>[14](https://iopscience.iop.org/article/10.1088/2057-1976/abc3a7)</sup> Alternative ISF collection methods, including skin biopsies, implanted wicks or capsules, suction blisters, and capillaries or needles with applied vacuum, are limited by their time-consuming nature, invasiveness, and small sample volumes, and vacuum methods yield highly varying ISF albumin concentrations, indicating that applied forces may alter ISF composition.<sup>[14](https://iopscience.iop.org/article/10.1088/2057-1976/abc3a7)</sup>\n\n## References\n\n1. [OFM Technology, JOANNEUM RESEARCH](https://www.joanneum.at/ofm/ofm-technology/)\n2. [Comparison of cerebral Open Flow Microperfusion and Microdialysis when sampling small lipophilic and small hydrophilic substances](https://www.sciencedirect.com/science/article/abs/pii/S0165027018302917)\n3. [Comparative Study of Dermal Pharmacokinetics Between Topical Drugs Using Open Flow Microperfusion in a Pig Model (Pharmaceutical Research, 2023)](https://link.springer.com/article/10.1007/s11095-023-03645-3)\n4. [Clinical applicability of dOFM devices for dermal sampling (Skin Research and Technology, 2013)](https://onlinelibrary.wiley.com/doi/10.1111/srt.12071)\n5. [Monitoring of Biofluids in Microsamples: Investigations for Glucose Monitoring using Open-Flow Microperfusion (Graz University of Technology thesis)](https://tugraz.elsevierpure.com/en/publications/monitoring-of-biofluids-in-microsamples-investigations-for-glucos/)\n6. [Open-flow microperfusion of subcutaneous adipose tissue for on-line continuous ex vivo measurement of glucose concentration](https://pubmed.ncbi.nlm.nih.gov/9203447/)\n7. [Open Flow Microperfusion as a Dermal Pharmacokinetic Approach to Evaluate Topical Bioequivalence (Clinical Pharmacokinetics, 2016)](https://link.springer.com/article/10.1007/s40262-016-0442-z)\n8. [Quantification of the Therapeutic Antibody Ocrelizumab in Mouse Brain Interstitial Fluid Using Cerebral Open Flow Microperfusion and Simultaneous Monitoring of the Blood–Brain Barrier Integrity (Pharmaceutics, 2023)](https://mdpi-res.com/d_attachment/pharmaceutics/pharmaceutics-15-01880/article_deploy/pharmaceutics-15-01880.pdf?version=1688451037)\n9. [Direct access to interstitial fluid in adipose tissue in humans by use of open-flow microperfusion](https://pubmed.ncbi.nlm.nih.gov/9950802/)\n10. [Dermal Open Flow Microperfusion (dOFM): Design, Evaluation, Research (Graz University of Technology thesis)](https://tugraz.elsevierpure.com/en/publications/dermal-open-flow-microperfusion-dofm-design-evaluation-research/)\n11. [Cerebral Open Flow Microperfusion to Monitor Drug Transport Across the Blood-Brain Barrier (Current Protocols, 2019)](https://currentprotocols.onlinelibrary.wiley.com/doi/10.1002/cpph.60)\n12. [Current Approaches to Monitor Macromolecules Directly from the Cerebral Interstitial Fluid (Pharmaceutics, 2022)](https://mdpi-res.com/d_attachment/pharmaceutics/pharmaceutics-14-01051/article_deploy/pharmaceutics-14-01051.pdf?version=1652424551)\n13. [Cerebral Open Flow Microperfusion (cOFM), PLOS ONE](https://journals.plos.org/plosone/article/file?id=10.1371%2Fjournal.pone.0098143&type=printable)\n14. [OFM-recirculation and OFM-suction: advanced in-vivo open flow microperfusion (OFM) methods for direct and absolute quantification of albumin in interstitial fluid (2020)](https://iopscience.iop.org/article/10.1088/2057-1976/abc3a7)\n15. [Cerebral open flow microperfusion (cOFM)-HILIC-HRMS platform for in vivo and in situ monitoring of tumor microenvironment in glioblastoma](https://www.sciencedirect.com/science/article/pii/S000326702500577X)\n16. [Predicting human subcutaneous bioavailability of monoclonal antibodies using an open flow microperfusion porcine model (KU Leuven repository record)](https://lirias.kuleuven.be/4279542)\n\n---\n*Topic: Encyclopedia › Life and health › Human health and medicine › Clinical assessment and procedures › Laboratory assays and specimen processing*\n\n*Initially written Sep 29, 2026 · Reviewed: Sep 30, 2026 · Edited: Sep 30, 2026; Oct 21, 2026 · Last review: Sep 30, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n",
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