Novel Method for Routine Ultrasound-Guided Serum Collection for Biomarker Analysis Around the Knee Joint

Background Biomarkers are essential tools in modern medicine, allowing stratification and monitoring of clinical care and treatment response. While systemic blood biomarkers, typically collected from the antecubital vein (AV), are widely used, their sensitivity for joint-specific pathologies such as osteoarthritis (OA) may be limited due to systemic dilution. At present, no serum biomarker reliably reflects the microenvironment of an affected joint in clinical practice. Although synovial fluid (SF) assessment can provide insights into localised pathology and are clinically used for diagnosis in crystal arthropathies and joint infections, their collection is invasive, painful, and carries risks, including infection, making repeated sampling impractical, limiting utility for monitoring treatment responses. This study introduces a novel ultrasound-guided venous sampling technique targeting the saphenous vein (SV) proximal to the knee joint as a less invasive alternative to SF aspiration, hypothesising that it may better reflect the joint-specific microenvironment. Methods A standardised gel model was used to train medically qualified researchers in ultrasound-guided venepuncture of vescles around 2-15 mm in diameter. Subsequently, 32 participants consented to blood sampling from the SV above the knee, with a proximally applied tourniquet to dilate vein diameter for easier venepuncture collection. Results The technique achieved serum collection in over 80% of consented individuals with minimal adverse effects (including n=2 minor bruising and n=1 transient nerve irritation). Key procedural insights included optimal site selection, appropriate pressure application, and effective tourniquet use. Discussion This method demonstrates feasibility, acceptability, and the potential for more localised sample collection, advancing biomarker research. Further validation, including paired SF comparisons, is required to confirm diagnostic utility and develop therapeutic strategies for joint-specific conditions.