Point-of-care sensors that enable the fast collection of information relevant to a patient’s health state can facilitate improved health access, reduce healthcare costs and improve the quality of healthcare delivery. In the diagnosis of sepsis — defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and the leading cause of in-patient death and of hospital readmission in the United States — predicting which infections will lead to life-threatening organ dysfunction and developing specific anti-sepsis treatments remain challenging because of the significant heterogeneity of the host response. Yet the use of point-of-care devices could reduce the time from the onset of a patient’s infection to the administration of appropriate therapeutics. In this Perspective, we describe the current state of point-of-care sensors for the diagnosis and monitoring of sepsis, and outline opportunities in the use of these devices to dramatically improve patient care.
Subscribe to Journal
Get full journal access for 1 year
only $8.67 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Fleischmann, C. et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am. J. Respir. Crit. Care Med. 193, 259–272 (2016).
Fleischmann, C. et al. The global burden of pediatric and neonatal sepsis: a systematic review. Lancet Respir. Med. 6, 223–230 (2018).
Van Dillen, J. et al. Maternal sepsis: epidemiology, etiology and outcome. Curr. Opin. Infect. Dis. 23, 249–254 (2010).
Lagu, T. et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit. Care Med. 40, 754–761 (2012).
Gaieski, D. F., Edwards, M., Kallan, K. J. & Carr, B. J. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit. Care Med. 41, 1167–1174 (2013).
Seymour, C. W. et al. Time to treatment and mortality during mandated emergency care for sepsis. N. Engl. J. Med. 376, 2235–2244 (2017).
Alam, N. et al. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir. Med. 6, 40–50 (2018).
Gander, R. M. et al. Impact of blood cultures drawn by phlebotomy on contamination rates and health care costs in a hospital emergency department. J. Clin. Microbiol. 47, 1021–1024 (2009).
Sitdikov, R. A. et al. Target capture system. US patent 9599610 (2014).
Puttaswamy, S., Lee, B. D. & Sengupta, S. Novel electrical method for early detection of viable bacteria in blood cultures. J. Clin. Microbiol. 49, 2286–2289 (2011).
Sengupta, S., Puttaswamy, S. & Chang, H. C. Rapid detection of viable bacteria system and method. US patent 8,635,028 (2014).
FAST technology. Qvella Corporation https://www.qvella.com/technology (2018).
LiDia. DNA Electronics http://www.dnae.com/lidia.html (2018).
Accelerate Pheno system. Accelerate Diagnostics http://acceleratediagnostics.com/products/accelerate-pheno-system/#features (2018).
Niemz, A., Ferguson, T. M. & Boyle, D. S. Point-of-care nucleic acid testing for infectious diseases. Trends Biotechnol. 29, 240–250 (2011).
Singer, M. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315, 801–810 (2016).
BioMérieux 510(k) Substantial Equivalence Determination Decision Memorandum K162827, VIDAS B·R·A·H·M·S PCT clearance submission to FDA (FDA, 2017).
Faix, J. D. Biomarkers of sepsis. Crit. Rev. Clin. Lab. Sci. 50, 23–36 (2013).
de Jong, E., van Oers, J. A., Beishuizen, A., Vos, P. & Vermeijden, W. J. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect. Dis. 16, 819–827 (2016).
Pierrakos, C. & Vincent, J. L. Sepsis biomarkers: a review. Crit. Care 14, R15 (2010).
Kibe, S., Adams, K. & Barlow, G. Diagnostic and prognostic biomarkers of sepsis in critical care. J. Antimicrob. Chemother. 66, ii33–ii40 (2010).
Schuetz, P. et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect. Dis. 18, 95–107 (2018).
Huang, D. T. et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N. Engl. J. Med. 379, 236–249 (2018).
Shapiro, N. I. et al. A prospective, multicenter derivation of a biomarker panel to assess risk of organ dysfunction, shock, and death in emergency department patients with suspected sepsis. Crit. Care Med. 37, 96–104 (2009).
Paulus, P., Jennewein, C. & Zacharowski, K. Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis? Biomarkers 16, S11–S21 (2011).
Angus, D. C. & Poll, T. Sepsis and septic shock. N. Engl. J. Med. 369, 840–851 (2013).
Hotchkiss, R. S. et al. Sepsis and septic shock. Nat. Rev. Dis. Primers 2, 16045 (2016).
Poll, T. V. D., van de Veerdonk, F. L., Scicluna, B. P. & Netea, M. G. The immunopathology of sepsis and potential therapeutic targets. Nat. Rev. Immunol. 17, 407–420 (2017).
Chauhan, N., Tiwari, S. & Jain, U. Potential biomarkers for effective screening of neonatal sepsis infections: an overview. Microb. Pathog. 107, 234–242 (2017).
Kolaczkowska, E. & Kubes, P. Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13, 159–175 (2013).
Seymour, C. W. et al. Delays from first medical contact to antibiotic administration for sepsis. Crit. Care Med. 45, 759–765 (2017).
Pitt, W. G. et al. Rapid separation of bacteria from blood — review and outlook. Biotechnol. Prog. 32, 823–839 (2016).
Mutlu, B. R. et al. Non-equilibrium inertial separation array for high-throughput, large-volume blood fractionation. Sci. Rep. 7, 9915 (2017).
Fachin, F. et al. Monolithic chip for high-throughput blood cell depletion to sort rare circulating tumor cells. Sci. Rep. 7, 10936 (2017).
Martel, J. M. et al. Continuous flow microfluidic bioparticle concentrator. Sci. Rep. 5, 11300 (2015).
Hassan, U., Watkins, N. N., Reddy, B., Damhorst, G. & Bashir, R. Microfluidic differential immuno-capture biochip for specific leukocyte counting. Nat. Protoc. 11, 714–726 (2016).
Hassan, U. et al. A microfluidic biochip for complete blood cell counts at the point-of-care. Technology 3, 201–213 (2015).
Hassan, U. et al. A point-of-care microfluidic biochip for quantification of CD64 expression from whole blood for sepsis stratification. Nat. Commun. 8, 15949 (2017).
Valera, E., Shia, W. W. & Bailey, R. C. Development and validation of an immunosensor for monocyte chemotactic protein 1 using a silicon photonic micro-ring resonator biosensing platform. Clin. Biochem. 49, 121–126 (2016).
Liu, D. et al. A fully integrated distance readout ELISA-chip for point-of-care testing with sample-in-answer-out capability. Biosens. Bioelectron. 96, 332–338 (2017).
Islam, F. et al. An electrochemical method for sensitive and rapid detection of FAM134B protein in colon cancer samples. Sci. Rep. 7, 133 (2017).
Tacke, F. et al. Levels of circulating miR-133a are elevated in sepsis and predict mortality in critically ill patients. Crit. Care Med. 42, 1096–1104 (2014).
Roderburg, C. et al. Circulating microRNA-150 serum levels predict survival in patients with critical illness and sepsis. PLoS ONE 8, e54612 (2013).
Bomsztyk, K. et al. Experimental acute lung injury induces multi-organ epigenetic modifications in key angiogenic genes implicated in sepsis-associated endothelial dysfunction. Crit. Care 19, 225 (2015).
Hur, S. C., Henderson-MacLennan, N. K., McCabec, E. R. B. & Carlo, D. D. Deformability based cell classification and enrichment using inertial microfluidics. Lab Chip 11, 912–920 (2011).
Wang, G. et al. Stiffness dependent separation of cells in a microfluidic device. PLoS ONE 8, e75901 (2013).
Rassaei, L., Olthuis, W., Tsujimura, S., Sudhölter, E. R. & van den Berg, A. Lactate biosensors: current status and outlook. Anal. Bioanal. Chem. 406, 123–137 (2014).
Angus, D. C. Defining sepsis: a case of bounded rationality and fuzzy thinking?. Am. J. Respir. Crit. Care Med. 194, 14–15 (2016).
Ellett, F. et al. Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil motility in a microfluidic assay. Nat. Biomed. Eng. 2, 207–214 (2018).
Jämsä, J., Huotari, V., Savolainen, E. R., Syrjälä, H. & Ala-Kokko, T. Analysis of the temperature affects on leukocyte surface antigen expression. J. Clin. Lab. Anal. 25, 118–125 (2011).
How to find and effectively use predicate devices. US Food and Drug Administration https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ucm134571.htm (2017).
Haak, B. W. & Wiersinga, W. J. The role of the gut microbiota in sepsis. Lancet 2, 135–143 (2017).
Dickson, R. P. et al. Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome. Nat. Microbiol. 1, 16113 (2016).
Budden, K. F. et al. Emerging pathogenic links between microbiota and the gut–lung axis. Nat. Rev. Microbiol. 15, 55–63 (2017).
Fired, J. On World Sepsis Day, a call for much-needed research funding. Noozhawk https://www.noozhawk.com/article/dr._jeffrey_fried_world_sepsis_day (2014).
Sepsis: a word to know, a meaning to learn. Sepsis Alliance News https://www.sepsis.org/sepsis-alliance-news/sepsis-word-know-meaning-learn/ (2017).
The authors thank B. Davis, J. Kumar, V. Reddi, J. Eardley, E. Iniguez, N. Topudurti, G. Damhorst and I. Taneja for useful discussions around clinical care for septic patients, technology development and data analytics.
B.R., R.B. and U.H. have financial interests in Prenosis Inc. The remaining authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Reddy, B., Hassan, U., Seymour, C. et al. Point-of-care sensors for the management of sepsis. Nat Biomed Eng 2, 640–648 (2018). https://doi.org/10.1038/s41551-018-0288-9
The potential of wastewater-based epidemiology as surveillance and early warning of infectious disease outbreaks
Current Opinion in Environmental Science & Health (2020)
Biomedical Microdevices (2020)
Nanoscale Advances (2020)
Lab on a Chip (2020)
A fully integrated bacterial pathogen detection system based on count-on-a-cartridge platform for rapid, ultrasensitive, highly accurate and culture-free assay
Biosensors and Bioelectronics (2020)