Surgical operations are intricate and invasive procedures that require continuous monitoring of the patient's biochemical profile. Point-of-care testing would allow healthcare professionals to identify abnormalities and make the necessary interventions to minimize the risk of complications and ensure patient safety. To this end, we report the development of a disposable and compact fully 3D-printed electrochemical cell incorporated into a medical scalpel (Lab-on-a-Scalpel), aiming to promote on-site (electro)chemical analysis in the operating theater. This multifunctional device minimizes the number of instruments needed during surgery and can be fabricated on-demand by using a desktop-sized 3D printer at a very low cost. The performance of the Lab-on-a-Scalpel sensing device was evaluated over various electrochemical techniques (cyclic voltammetry, amperometry, and differential pulse voltammetry) and different setups (stirring, drop-volume analysis, polarization potentials, etc.) for the determination of epinephrine. Results showed attractive analytical figures-of-merit, with the limit of detection (LOD) reaching 0.13 μM, and high accuracy in recovery studies conducted on artificial blood samples. Our findings suggest that Lab-on-a-Scalpel is a valuable tool that enables near-patient diagnostics with a minimum sample volume and holds promise to become an essential tool for robotic-assisted surgery.

Department of Inorganic Chemistry University of Chemistry and Technology Prague Technicka 5 Prague 6 16628 Czech Republic

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Cheng H., Clymer J. W., Po-Han Chen B., Sadeghirad B., Ferko N. C., Cameron C. G., Hinoul P.. Prolonged Operative Duration Is Associated with Complications: A Systematic Review and Meta-Analysis. Journal of Surgical Research. 2018;229:134–144. doi: 10.1016/j.jss.2018.03.022. PubMed DOI

Aseni P., Orsenigo S., Storti E., Pulici M., Arlati S.. Current Concepts of Perioperative Monitoring in High-Risk Surgical Patients: A Review. Patient Saf. Surg. 2019;13:32. doi: 10.1186/s13037-019-0213-5. PubMed DOI PMC

Noor, Z. M. Life-Threatening Cardiac Arrhythmias during Anesthesia and Surgery. In Cardiac Arrhythmias-Translational Approach from Pathophysiology to Advanced Care; IntechOpen: 2022.

Finnerty C. C., Mabvuure N. T., Ali A., Kozar R. A., Herndon D. N., Martindale R. G., McClave S. A., Kozar R. A., Heyland D. K.. The Surgically Induced Stress Response. J. Parenter. Enteral Nutr. 2013;37:21S–29S. doi: 10.1177/0148607113496117. PubMed DOI PMC

Preeshagul I., Gharbaran R., Jeong K. H., Abdel-Razek A., Lee L. Y., Elman E., Suh K. S.. Potential Biomarkers for Predicting Outcomes in CABG Cardiothoracic Surgeries. J. Cardiothorac. Surg. 2013;8:176. doi: 10.1186/1749-8090-8-176. PubMed DOI PMC

Nourie N., Ghaleb R., Lefaucheur C., Louis K.. Toward Precision Medicine: Exploring the Landscape of Biomarkers in Acute Kidney Injury. Biomolecules. 2024;14:82. doi: 10.3390/biom14010082. PubMed DOI PMC

Shushan B.. A Review of Clinical Diagnostic Applications of Liquid Chromatography- Tandem Mass Spectrometry. Mass Spectrom Rev. 2010;29:930–944. doi: 10.1002/mas.20295. PubMed DOI

Sahu R. K., Mordechai S.. Spectroscopic Techniques in Medicine: The Future of Diagnostics. Appl. Spectrosc Rev. 2016;51:484–499. doi: 10.1080/05704928.2016.1157809. DOI

Tzianni Ε. I., Moutsios I., Moschovas D., Avgeropoulos A., Govaris K., Panagiotidis L., Prodromidis M. I.. Smartphone Paired SIM Card-Type Integrated Creatinine Biosensor. Biosens Bioelectron. 2022;207:114204. doi: 10.1016/j.bios.2022.114204. PubMed DOI

Tzianni E. I., Hrbac J., Christodoulou D. K., Prodromidis M. I.. A Portable Medical Diagnostic Device Utilizing Free-Standing Responsive Polymer Film-Based Biosensors and Low-Cost Transducer for Point-of-Care Applications. Sens Actuators B Chem. 2020;304:127356. doi: 10.1016/j.snb.2019.127356. DOI

Christodouleas D. C., Kaur B., Chorti P.. From Point-of-Care Testing to EHealth Diagnostic Devices (EDiagnostics) ACS Cent Sci. 2018;4:1600–1616. doi: 10.1021/acscentsci.8b00625. PubMed DOI PMC

Rhee A. J., Kahn R. A.. Laboratory Point-of-Care Monitoring in the Operating Room. Current Opinion in Anaesthesiology. 2010;23:741–748. doi: 10.1097/ACO.0b013e32834015bd. PubMed DOI

Anik, U. Electrochemical Medical Biosensors for POC Applications. In Medical Biosensors for Point of Care (POC) Applications; Woodhead Publishing: 2017; pp 275–292.

Ramos D. L. O., de Faria L. V., Alves D. A. C., Muñoz R. A. A., dos Santos W. T. P., Richter E. M.. Electrochemical Platform Produced by 3D Printing for Analysis of Small Volumes Using Different Electrode Materials. Talanta. 2023;265:124832. doi: 10.1016/j.talanta.2023.124832. PubMed DOI

Cardoso R. M., Kalinke C., Rocha R. G., dos Santos P. L., Rocha D. P., Oliveira P. R., Janegitz B. C., Bonacin J. A., Richter E. M., Munoz R. A. A.. Additive-Manufactured (3D-Printed) Electrochemical Sensors: A Critical Review. Anal. Chim. Acta. 2020;1118:73–91. doi: 10.1016/j.aca.2020.03.028. PubMed DOI

Katseli V., Thomaidis N., Economou A., Kokkinos C.. Miniature 3D-Printed Integrated Electrochemical Cell for Trace Voltammetric Hg­(II) Determination. Sens Actuators B Chem. 2020;308:127715. doi: 10.1016/j.snb.2020.127715. DOI

Kalinke C., Neumsteir N. V., Roberto de Oliveira P., Janegitz B. C., Bonacin J. A.. Sensing of L-Methionine in Biological Samples through Fully 3D-Printed Electrodes. Anal. Chim. Acta. 2021;1142:135–142. doi: 10.1016/j.aca.2020.10.034. PubMed DOI

Koukouviti E., Plessas A. K., Pagkali V., Economou A., Papaefstathiou G. S., Kokkinos C.. 3D-Printed Electrochemical Glucose Device with Integrated Fe­(II)-MOF Nanozyme. Microchim. Acta. 2023;190:274. doi: 10.1007/s00604-023-05860-6. PubMed DOI PMC

Liu M. M., Zhong Y., Chen Y., Wu L. N., Chen W., Lin X. H., Lei Y., Liu A. L.. Electrochemical Monitoring the Effect of Drug Intervention on PC12 Cell Damage Model Cultured on Paper-PLA 3D Printed Device. Anal. Chim. Acta. 2022;1194:339409. doi: 10.1016/j.aca.2021.339409. PubMed DOI

de Matos Morawski F., Martins G., Ramos M. K., Zarbin A. J. G., Blanes L., Bergamini M. F., Marcolino-Junior L. H.. A Versatile 3D Printed Multi-Electrode Cell for Determination of Three COVID-19 Biomarkers. Anal. Chim. Acta. 2023;1258:341169. doi: 10.1016/j.aca.2023.341169. PubMed DOI

Rosenberg P. H., Veering B. T., Urmey W. F.. Maximum Recommended Doses of Local Anesthetics: A Multifactorial Concept. Reg. Anesth. Pain Med. 2004;29:564–575. doi: 10.1016/j.rapm.2004.08.003. PubMed DOI

Hassanpour S. E., Zirakzadeh H., Aghajani Y.. The Effect of Subcutaneous Epinephrine Dosage on Blood Loss in Surgical Incisions. World J. Plast Surg. 2020;9:309–312. doi: 10.29252/wjps.9.3.309. PubMed DOI PMC

Koukouviti E., Kokkinos C.. 3D Printed Enzymatic Microchip for Multiplexed Electrochemical Biosensing. Anal. Chim. Acta. 2021;1186:339114. doi: 10.1016/j.aca.2021.339114. PubMed DOI

Papavasileiou A. V., Děkanovský L., Chacko L., Wu B., Luxa J., Regner J., Paštika J., Koňáková D., Sofer Z.. Unraveling the Versatility of Carbon Black – Polylactic Acid (CB/PLA) 3D-Printed Electrodes via Sustainable Electrochemical Activation. Small Methods. 2025:2402214. doi: 10.1002/smtd.202402214. PubMed DOI

Manzanares Palenzuela C. L., Novotný F., Krupička P., Sofer Z., Pumera M.. 3D-Printed Graphene/Polylactic Acid Electrodes Promise High Sensitivity in Electroanalysis. Anal. Chem. 2018;90:5753–5757. doi: 10.1021/acs.analchem.8b00083. PubMed DOI

Carvalho M. S., Rocha R. G., Nascimento A. B., Araújo D. A. G., Paixão T. R. L. C., Lopes O. F., Richter E. M., Muñoz R. A. A.. Enhanced Electrochemical Performance of 3D-Printed Electrodes via Blue-Laser Irradiation and (Electro)­Chemical Treatment. Electrochim. Acta. 2024;506:144995. doi: 10.1016/j.electacta.2024.144995. DOI

Cardoso R. M., Castro S. V. F., Silva M. N. T., Lima A. P., Santana M. H. P., Nossol E., Silva R. A. B., Richter E. M., Paixão T. R. L. C., Muñoz R. A. A.. 3D-Printed Flexible Device Combining Sampling and Detection of Explosives. Sens Actuators B Chem. 2019;292:308–313. doi: 10.1016/j.snb.2019.04.126. DOI

Hernández-Rodríguez J. F., Trachioti M. G., Hrbac J., Rojas D., Escarpa A., Prodromidis M. I.. Spark-Discharge-Activated 3D-Printed Electrochemical Sensors. Anal. Chem. 2024;96:10127–10133. doi: 10.1021/acs.analchem.4c01249. PubMed DOI PMC

Richter E. M., Rocha D. P., Cardoso R. M., Keefe E. M., Foster C. W., Munoz R. A. A., Banks C. E.. Complete Additively Manufactured (3D-Printed) Electrochemical Sensing Platform. Anal. Chem. 2019;91:12844–12851. doi: 10.1021/acs.analchem.9b02573. PubMed DOI

Kalinke C., Neumsteir N. V., de Oliveira Aparecido G., de Barros Ferraz T. V., dos Santos P. L., Janegitz B. C., Bonacin J. A.. Comparison of Activation Processes for 3D Printed PLA-Graphene Electrodes: Electrochemical Properties and Application for Sensing of Dopamine. Analyst. 2020;145:1207. doi: 10.1039/C9AN01926J. PubMed DOI

Honeychurch K. C., Rymansaib Z., Iravani P.. Anodic Stripping Voltammetric Determination of Zinc at a 3-D Printed Carbon Nanofiber–Graphite–Polystyrene Electrode Using a Carbon Pseudo-Reference Electrode. Sens Actuators B Chem. 2018;267:476–482. doi: 10.1016/j.snb.2018.04.054. DOI

Yi H., Li Z., Li K.. Application of Mesoporous SiO2-Modified Carbon Paste Electrode for Voltammetric Determination of Epinephrine. Russian Journal of Electrochemistry. 2013;49:1073–1080. doi: 10.1134/S1023193512080046. DOI

Sipuka D. S., Sebokolodi T. I., Olorundare F. O. G., Muzenda C., Nkwachukwu O. V., Nkosi D., Arotiba O. A.. Electrochemical Sensing of Epinephrine on a Carbon Nanofibers and Gold Nanoparticle-Modified Electrode. Electrocatalysis. 2023;14:9–17. doi: 10.1007/s12678-022-00769-9. DOI

Bacil R. P., Garcia P. H. M., Serrano S. H. P.. New Insights on the Electrochemical Mechanism of Epinephrine on Glassy Carbon Electrode. J. Electroanal. Chem. 2022;908:116111. doi: 10.1016/j.jelechem.2022.116111. DOI

Lavanya N., Fazio E., Neri F., Bonavita A., Leonardi S. G., Neri G., Sekar C.. Simultaneous Electrochemical Determination of Epinephrine and Uric Acid in the Presence of Ascorbic Acid Using SnO2/Graphene Nanocomposite Modified Glassy Carbon Electrode. Sens Actuators B Chem. 2015;221:1412–1422. doi: 10.1016/j.snb.2015.08.020. DOI

Canevari T. C., Nakamura M., Cincotto F. H., De Melo F. M., Toma H. E.. High Performance Electrochemical Sensors for Dopamine and Epinephrine Using Nanocrystalline Carbon Quantum Dots Obtained under Controlled Chronoamperometric Conditions. Electrochim. Acta. 2016;209:464–470. doi: 10.1016/j.electacta.2016.05.108. DOI

Teradale A. B., Lamani S. D., Ganesh P. S., Kumara Swamy B. E., Das S. N.. Niacin Film Coated Carbon Paste Electrode Sensor for the Determination of Epinephrine in Presence of Uric Acid: A Cyclic Voltammetric Study. Analytical Chemistry Letters. 2017;7:748–764. doi: 10.1080/22297928.2017.1396917. DOI

Shankar S. S., Shereema R. M., Rakhi R. B.. Electrochemical Determination of Adrenaline Using MXene/Graphite Composite Paste Electrodes. ACS Appl. Mater. Interfaces. 2018;10:43343–43351. doi: 10.1021/acsami.8b11741. PubMed DOI

Gopal P., Narasimha G., Reddy T. M.. Development, Validation and Enzyme Kinetic Evaluation of Multi Walled Carbon Nano Tubes Mediated Tyrosinase Based Electrochemical Biosensing Platform for the Voltammetric Monitoring of Epinephrine. Process Biochemistry. 2020;92:476–485. doi: 10.1016/j.procbio.2020.02.006. DOI

Li Z., Guo Y., Yue H., Gao X., Huang S., Zhang X., Yu Y., Zhang H., Zhang H.. Electrochemical Determination of Epinephrine Based on Ti3C2Tx MXene-Reduced Graphene Oxide/ITO Electrode. J. Electroanal. Chem. 2021;895:115425. doi: 10.1016/j.jelechem.2021.115425. DOI

Pecheu C. N., Tchieda V. K., Tajeu K. Y., Jiokeng S. L. Z., Lesch A., Tonle I. K., Ngameni E., Janiak C.. Electrochemical Determination of Epinephrine in Pharmaceutical Preparation Using Laponite Clay-Modified Graphene Inkjet-Printed Electrode. Molecules. 2023;28:5487. doi: 10.3390/molecules28145487. PubMed DOI PMC

da Silva V. A. O. P., Stefano J. S., Kalinke C., Bonacin J. A., Janegitz B. C.. Additive Manufacturing Sensor for Stress Biomarker Detection. Chemosensors. 2023;11:306. doi: 10.3390/chemosensors11050306. DOI

Rantataro S., Ferrer Pascual L., Laurila T.. Ascorbic Acid Does Not Necessarily Interfere with the Electrochemical Detection of Dopamine. Sci. Rep. 2022;12:20225. doi: 10.1038/s41598-022-24580-0. PubMed DOI PMC

Colan J., Davila A., Zhu Y., Aoyama T., Hasegawa Y.. OpenRST: An Open Platform for Customizable 3D Printed Cable-Driven Robotic Surgical Tools. IEEE Access. 2023;11:6092–6105. doi: 10.1109/ACCESS.2023.3236821. DOI