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Photonic monitoring of treatment during infection and sepsis: development of new detection strategies and potential clinical applications


Despite the strong decline in the infection-associated mortality since the development of the first antibiotics, infectious diseases are still a major cause of death in the world. With the rising number of antibiotic-resistant pathogens, the incidence of deaths caused by infections may increase strongly in the future. Survival rates in sepsis, which occurs when body response to infections becomes uncontrolled, are still very poor if an adequate therapy is not initiated immediately. Therefore, approaches to monitor the treatment efficacy are crucially needed to adapt therapeutic strategies according to the patient’s response. An increasing number of photonic technologies are being considered for diagnostic purpose and monitoring of therapeutic response; however many of these strategies have not been introduced into clinical routine, yet. Here, we review photonic strategies to monitor response to treatment in patients with infectious disease, sepsis, and septic shock. We also include some selected approaches for the development of new drugs in animal models as well as new monitoring strategies which might be applicable to evaluate treatment response in humans in the future.

Label-free probing of blood properties using photonics

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  1. 1.

    Martens E, Demain AL. The antibiotic resistance crisis, with a focus on the United States. J Antibiot (Tokyo). 2017;70:520–526.

  2. 2.

    Morens DM, Folkers GK, Fauci AS. Emerging infections: a perpetual challenge. Lancet Infect Dis. 2008; 8:710–719.

  3. 3.

    Dodds DR. Antibiotic resistance: a current epilogue. Biochem Pharmacol. 2017;134:139–146.

  4. 4.

    Barrett JF. MRSA: status and prospects for therapy? An evaluation of key papers on the topic of MRSA and antibiotic resistance. Expert Opin Ther Targets. 2004;8:515–519.

  5. 5.

    Cohen J, Vincent JL, Adhikari NKJ, Machado FR, Angus DC, Calandra T, Jaton K, Giulieri S, Delaloye J, Opal S, Tracey K, van der Poll T, Pelfrene E. Sepsis: a roadmap for future research. Lancet Infect Dis. 2015;15:581–614.

  6. 6.

    Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ (Clinical Research Ed). 2016;353:i1585.

  7. 7.

    Ince C. The microcirculation is the motor of sepsis. Crit Care. 2005;9:S13.

  8. 8.

    Lush CW, Kvietys PR. Microvascular dysfunction in sepsis. Microcirculation 2000;7:83–101.

  9. 9.

    van der Poll T. Future of sepsis therapies. Crit Care. 2016;20:106.

  10. 10.

    Bahreini M. Role of optical spectroscopic methods in neuro-oncological sciences. J Lasers Med Sci. 2015;6: 51–61.

  11. 11.

    Shah K, Jacobs A, Breakefield XO, Weissleder R. Molecular imaging of gene therapy for cancer. Gene Ther. 2004;11:1175–1187.

  12. 12.

    Zhao Z, Yan R, Yi X, Li J, Rao J, Guo Z, Yang Y, Li W, Li YQ, Chen C. Bacteria-activated theranostic nanoprobes against methicillin-resistant Staphylococcus aureus infection. ACS nano 2017;11:4428–4438.

  13. 13.

    Solomon M, Liu Y, Berezin MY, Achilefu S. Optical imaging in cancer research: basic principles, tumor detection, and therapeutic monitoring. Med Princ Pract. 2011;20:397–415.

  14. 14.

    Sikkandhar MG, Nedumaran AM, Ravichandar R, Singh S, Santhakumar I, Goh ZC, Mishra S, Archunan G, Gulys B, Padmanabhan P. Theranostic probes for targeting tumor microenvironment: an overview. Int J Mol Sci. 2017;18(5):1036. https://doi.org/https://doi.org/10.3390/ijms18051036.

  15. 15.

    Bengel FM. 2017. Issue noninvasive molecular imaging and theranostic probes: New concepts in myocardial imaging. Methods.

  16. 16.

    Pene F, Courtine E, Cariou A, Mira JP. Toward theragnostics. Crit Care Med. 2009;37:S50–S58.

  17. 17.

    Heuker M, Gomes A, van Dijl JM, van Dam GM, Friedrich AW, Sinha B, van Oosten M. Preclinical studies and prospective clinical applications for bacteria-targeted imaging: the future is bright. Clin Transl Imaging. 2016;4:253–264.

  18. 18.

    Hu J, Bohn PW. Optical biosensing of bacteria and bacterial communities. Journal of Analysis and Testing. 2017;1:4.

  19. 19.

    Navalkissoor S, Nowosinska E, Gnanasegaran G, Buscombe JR. Single-photon emission computed tomography-computed tomography in imaging infection. Nucl Med Commun. 2013;34:283–290.

  20. 20.

    De Backer D, Donadello K. Assessment of microperfusion in sepsis. Minerva Anestesiol. 2015;81:533–540.

  21. 21.

    Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation. Crit Care. 2015;19 (Suppl 3):S8.

  22. 22.

    Gruartmoner G, Mesquida J, Ince C. Microcirculatory monitoring in septic patients: Where do we stand? Med Intensiva. 2017;41:44–52.

  23. 23.

    Pozo MO, Kanoore Edul VS, Ince C, Dubin A. Comparison of different methods for the calculation of the microvascular flow index. Crit Care Res Pract. 2012;2012:102483.

  24. 24.

    Groner W, Winkelman JW, Harris AG, Ince C, Bouma GJ, Messmer K, Nadeau RG. Orthogonal polarization spectral imaging: a new method for study of the microcirculation. Nat Med. 1999;5:1209–1212.

  25. 25.

    Cerny V, Turek Z, Parizkova R. Orthogonal polarization spectral imaging. Physiol Res. 2007;56:141–147.

  26. 26.

    De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166:98–104.

  27. 27.

    De Backer D, Verdant C, Chierego M, Koch M, Gullo A, Vincent JL. Effects of drotrecogin alfa activated on microcirculatory alterations in patients with severe sepsis. Crit Care Med. 2006;34:1918–1924.

  28. 28.

    Goedhart PT, Khalilzada M, Bezemer R, Merza J, Ince C. Sidestream dark field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation. Opt Express. 2007;15:15101.

  29. 29.

    Jhanji S, Stirling S, Patel N, Hinds CJ, Pearse RM. The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock. Crit Care Med. 2009;37:1961–1966.

  30. 30.

    He X, Su F, Velissaris D, Salgado DR, de Souza Barros D, Lorent S, Taccone FS, Vincent JL, De Backer D. Administration of tetrahydrobiopterin improves the microcirculation and outcome in an ovine model of septic shock. Crit Care Med. 2012;40:2833–2840.

  31. 31.

    Sherman H, Klausner S, Cook WA. Incident dark-field illumination: a new method for microcirculatory study. Angiology. 1971;22:295–303.

  32. 32.

    Aykut G, Veenstra G, Scorcella C, Ince C, Boerma C. Cytocam-idf (incident dark field illumination) imaging for bedside monitoring of the microcirculation. Intensive Care Med Exp. 2015;3:40.

  33. 33.

    Hutchings S, Watts S, Kirkman E. The cytocam video microscope. A new method for visualising the microcirculation using incident dark field technology. Clin Hemorheol Microcirc. 2016;62:261–271.

  34. 34.

    Boas DA, Dunn AK. Laser speckle contrast imaging in biomedical optics. J Biomed Opt. 2010;15: 011109–011109.

  35. 35.

    Richards LM, Kazmi SS, Davis JL, Olin KE, Dunn AK. Low-cost laser speckle contrast imaging of blood flow using a webcam. Biomed Opt Express. 2013;4:2269–2283.

  36. 36.

    Dunn AK. Laser speckle contrast imaging of cerebral blood flow. Ann Biomed Eng. 2012;40:367–377.

  37. 37.

    Nadort A, Kalkman K, van Leeuwen TG, Faber DJ. Quantitative blood flow velocity imaging using laser speckle flowmetry. Sci Rep. 2016;6:25258.

  38. 38.

    Sand CA, Starr A, Wilder CDE, Rudyk O, Spina D, Thiemermann C, Treacher DF, Nandi M. Quantification of microcirculatory blood flow: a sensitive and clinically relevant prognostic marker in murine models of sepsis. J Appl Physiol. 2015;118:344–354.

  39. 39.

    Wu Y, Ren J, Zhou B, Ding C, Chen J, Wang G, Gu G, Liu S, Li J. Laser speckle contrast imaging for measurement of hepatic microcirculation during the sepsis: a novel tool for early detection of microcirculation dysfunction. Microvasc Res. 2015;97:137–146.

  40. 40.

    Assadi A, Desebbe O, Kaminski C, Rimmel T , Bnatir F, Goudable J, Chassard D, Allaouchiche B. Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock. Br J Anaesth. 2008;100:55–65.

  41. 41.

    Jacquet-Lagrèze M, Allaouchiche B, Restagno D, Paquet C, Ayoub JY, Etienne J, Vandenesch F, Dauwalder O, Bonnet JM, Junot S. Gut and sublingual microvascular effect of esmolol during septic shock in a porcine model. Crit Care. 2015;19:241.

  42. 42.

    Birnbaum J, Klotz E, Spies CD, Lorenz B, Stuebs P, Hein OV, Grundling M, Pavlovic D, Usichenko T, Wendt M, Kox WJ, Lehmann C. Effects of dopexamine on the intestinal microvascular blood flow and leukocyte activation in a sepsis model in rats. Crit Care. 2006;10:R117.

  43. 43.

    Favory R, Poissy J, Alves I, Guerry MJ, Lemyze M, Parmentier-Decrucq E, Duburcq T, Mathieu D. Activated protein C improves macrovascular and microvascular reactivity in human severe sepsis and septic shock. Shock. 2013;40:512–518.

  44. 44.

    Krejci V, Hiltebrand LB, Sigurdsson GH. Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis. Crit Care Med. 2006;34:1456–1463.

  45. 45.

    Lehmann C, Zhou J, Schuster L, Götz F, Wegner A, Cerny V, Pavlovic D, Robertson GS. Effect of deletion of cIAP2 on intestinal microcirculation in mouse endotoxemia and polybacterial sepsis. Shock. 2014; 41:454–457.

  46. 46.

    Rosengarten B, Wolff S, Klatt S, Schermuly RT. Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model. Crit Care. 2009;13:R139.

  47. 47.

    Macdonald SPJ, Brown SGA. Near-infrared spectroscopy in the assessment of suspected sepsis in the emergency department. Emerg Med J. 2015;32:404–408.

  48. 48.

    Neto AS, Pereira VGM, Manetta JA, Espósito DC, Schultz MJ. Association between static and dynamic thenar near-infrared spectroscopy and mortality in patients with sepsis. J Trauma Acute Care Surg. 2014; 76:226–233.

  49. 49.

    Vorwerk C, Coats TJ. The prognostic value of tissue oxygen saturation in emergency department patients with severe sepsis or septic shock. Emerg Med J. 2011;29:699–703.

  50. 50.

    Wood M, Song A, Maslove D, Ferri C, Howes D, Muscedere J, Boyd JG. Brain tissue oxygenation in patients with septic shock: a feasibility study. Can J Neurol Sci. 2015;43:65–73.

  51. 51.

    Georger JF, Hamzaoui O, Chaari A, Maizel J, Richard C, Teboul JL. Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients. Intensive Care Med. 2010;36:1882–1889.

  52. 52.

    Dubin A, Pozo MO, Casabella CA, Pálizas F, Murias G, Moseinco MC, Edul VSK, Pálizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care. 2009;13:R92.

  53. 53.

    Donati A, Romanelli M, Botticelli L, Valentini A, Gabbanelli V, Nataloni S, Principi T, Pelaia P, Bezemer R, Ince C. Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy. Crit Care. 2009;13:S12.

  54. 54.

    Wallace MB, Wax A, Roberts DN, Graf RN. Reflectance spectroscopy. Gastrointest Endosc Clin N Am 2009;19:233–242.

  55. 55.

    Leung FW. Endoscopic reflectance spectrophotometry and visible light spectroscopy in clinical gastrointestinal studies. Dig Dis Sci. 2008;53:1669–1677.

  56. 56.

    Valdez TA, Spegazzini N, Pandey R, Longo K, Grindle C, Peterson D, Barman I. Multi-color reflectance imaging of middle ear pathology in vivo. Anal Bioanal Chem. 2015;407:3277–3283.

  57. 57.

    Sakr Y, Gath V, Oishi J, Klinzing S, Simon TP, Reinhart K, Marx G. Characterization of buccal microvascular response in patients with septic shock. Eur J Anaesthesiol. 2010;27:388–394.

  58. 58.

    Schwarte LA, Picker O, Bornstein SR, Fournell A, Scheeren TWL. Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs. Crit Care Med. 2005;33:135–42. discussion 246–7.

  59. 59.

    Shapiro NI, Angus DC. A review of therapeutic attempts to recruit the microcirculation in patients with sepsis. Minerva Anestesiol. 2014;80:225–235.

  60. 60.

    Bezemer R, Bartels SA, Bakker J, Ince C. Clinical review: clinical imaging of the sublingual microcirculation in the critically ill–where do we stand? Crit Care. 2012;16:224.

  61. 61.

    Spronk PE, Zandstra DF, Ince C. Bench-to-bedside review: sepsis is a disease of the microcirculation. Crit Care. 2004;8:462.

  62. 62.

    De Backer D, Orbegozo Cortes D, Donadello K, Vincent JL. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence. 2014;5:73–79.

  63. 63.

    Morelli A, Passariello M. Hemodynamic coherence in sepsis. Best Pract Res Clin Anaesthesiol. 2016;30: 453–463.

  64. 64.

    Nakajima Y, Baudry N, Duranteau J, Vicaut E. Effects of vasopressin, norepinephrine, and L-arginine on intestinal microcirculation in endotoxemia. Crit Care Med 2006;34:1752–1757.

  65. 65.

    Marechal X, Favory R, Joulin O, Montaigne D, Hassoun S, Decoster B, Zerimech F, Neviere R. Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress. Shock. 2008;29:572–576.

  66. 66.

    Hoffmann JN, Vollmar B, Römisch J, Inthorn D, Schildberg FW, Menger MD. Antithrombin effects on endotoxin-induced microcirculatory disorders are mediated mainly by its interaction with microvascular endothelium. Crit Care Med. 2002;30:218–225.

  67. 67.

    Tyml K, Li F, Wilson JX. Delayed ascorbate bolus protects against maldistribution of microvascular blood flow in septic rat skeletal muscle. Crit Care Med. 2005;33:1823–1828.

  68. 68.

    Obonyo NG, Fanning JP, Ng ASY, Pimenta LP, Shekar K, Platts DG, Maitland K, Fraser JF. Effects of volume resuscitation on the microcirculation in animal models of lipopolysaccharide sepsis: a systematic review. Intensive Care Med Exp. 2016;4:38.

  69. 69.

    Zanini GM, Cabrales P, Barkho W, Frangos JA, Carvalho LJM. Exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during Plasmodium berghei ANKA infection in mice. J Neuroinflammation. 2011;8:66.

  70. 70.

    Nacer A, Movila A, Sohet F, Girgis NM, Gundra UM, Loke P, Daneman R, Frevert U. Experimental cerebral malaria pathogenesis–hemodynamics at the blood–brain barrier. PLoS Pathog. 2014;10: e1004528.

  71. 71.

    Cabrales P, Zanini GM, Meays D, Frangos JA, Carvalho LJM. Nitric oxide protection against murine cerebral malaria is associated with improved cerebral microcirculatory physiology. J Infect Dis. 2011; 203:1454–1463.

  72. 72.

    Wang Z, Holthoff JH, Seely KA, Pathak E, Spencer HJ, Gokden N, Mayeux PR. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsis-induced renal microcirculatory failure and acute kidney injury. Am J Pathol. 2012;180:505–516.

  73. 73.

    Wang Z, Sims CR, Patil NK, Gokden N, Mayeux PR. Pharmacologic targeting of sphingosine-1-phosphate receptor 1 improves the renal microcirculation during sepsis in the mouse. J Pharmacol Exp Ther. 2014;352:61–66.

  74. 74.

    Gupta A, Rhodes GJ, Berg DT, Gerlitz B, Molitoris BA, Grinnell BW. Activated protein C ameliorates LPS-induced acute kidney injury and downregulates renal INOS and angiotensin 2. Am J Physiol Renal Physiol. 2007;293:F245–F254.

  75. 75.

    Strnad P, Tacke F, Koch A, Trautwein C. Liver - guardian, modifier and target of sepsis. Nat Rev Gastroenterol Hepatol. 2017;14:55–66.

  76. 76.

    Yan J, Li S, Li S. The role of the liver in sepsis. Int Rev Immunol. 2014;33:498–510.

  77. 77.

    Bunchorntavakul C, Chamroonkul N, Chavalitdhamrong D. Bacterial infections in cirrhosis: a critical review and practical guidance. World J Hepatol. 2016;8:307–321.

  78. 78.

    Bauer M, Press AT, Trauner M. The liver in sepsis: patterns of response and injury. Curr Opin Crit Care. 2013;19:123–127.

  79. 79.

    Vos JJ, Wietasch JKG, Absalom AR, Hendriks HGD, Scheeren TWL. Green light for liver function monitoring using indocyanine green? An overview of current clinical applications. Anaesthesia. 2014;69:1364–1376.

  80. 80.

    Halle BM, Poulsen TD, Pedersen HP. Indocyanine green plasma disappearance rate as dynamic liver function test in critically ill patients. Acta Anaesthesiol Scand. 2014;58:1214–1219.

  81. 81.

    Rank N, Michel C, Haertel C, Lenhart A, Welte M, Meier-Hellmann A, Spies C. N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study. Crit Care Med. 2000;28:3799–3807.

  82. 82.

    Levesque E, Martin E, Dudau D, Lim C, Dhonneur G, Azoulay D. Current use and perspective of indocyanine green clearance in liver diseases. Anaesth Crit Care Pain Med. 2016;35:49–57.

  83. 83.

    Imai T, Takahashi K, Goto F, Morishita Y. Measurement of blood concentration of indocyanine green by pulse dye densitometry–comparison with the conventional spectrophotometric method. J Clin Monit Comput. 1998; 14:477–484.

  84. 84.

    Lehmann C, Taymoorian K, Wauer H, Krausch D, Birnbaum J, Kox WJ. Effects of the stable prostacyclin analogue iloprost on the plasma disappearance rate of indocyanine green in human septic shock. Intensive Care Med. 2000;26:1557–1560.

  85. 85.

    Birnbaum J, Lehmann C, Taymoorian K, Krausch D, Wauer H, Grndling M, Spies C, Kox WJ. The effect of dopexamine and iloprost on plasma disappearance rate of indocyanine green in patients in septic shock. Der Anaesthesist. 2003;52:1014–1019.

  86. 86.

    Zhang XW, Xie JF, Liu AR, Huang YZ, Guo FM, Yang CS, Yang Y, Qiu HB. Hepatic perfusion alterations in septic shock patients: impact of early goal-directed therapy. Chin Med J (Engl). 2016;129: 1666.

  87. 87.

    Kortgen A, Paxian M, Werth M, Recknagel P, Rauchfuss F, Lupp A, Krenn CG, Mller D, Claus RA, Reinhart K, Settmacher U, Bauer M. Prospective assessment of hepatic function and mechanisms of dysfunction in the critically ill. Shock. 2009;32:358–365.

  88. 88.

    Sauer M, Altrichter J, Haubner C, Pertschy A, Wild T, Do F, Mencke T, Thomsen M, Ehler J, Henschel J, Do S, Koch S, Richter G, Nldge-schomburg G, Mitzner SR. Bioartificial therapy of sepsis: changes of norepinephrine-dosage in patients and influence on dynamic and cell-based liver tests during extracorporeal treatments. Biomed Res Int. 2016;2016:7056492.

  89. 89.

    Guérin JP, Levraut J, Samat-Long C, Leverve X, Grimaud D, Ichai C. Effects of dopamine and norepinephrine on systemic and hepatosplanchnic hemodynamics, oxygen exchange, and energy balance in vasoplegic septic patients. Shock 2005;23:18–24.

  90. 90.

    Sarin SK, Choudhury A. Acute-on-chronic liver failure: terminology, mechanisms and management. Nat Rev Gastroenterol Hepatol. 2016;13:131.

  91. 91.

    Galler K, Schleser F, Fröhlich E, Requardt RP, Kortgen A, Bauer M, Popp J, Neugebauer U. Exploitation of the hepatic stellate cell Raman signature for their detection in native tissue samples. Integr Biol. 2014;6:946–956.

  92. 92.

    Galler K, Requardt RP, Glaser U, Markwart R, Bocklitz T, Bauer M, Popp J, Neugebauer U. Single cell analysis in native tissue: Quantification of the retinoid content of hepatic stellate cells. Sci Rep. 2016; 6:24155. https://doi.org/10.1038/srep24155.

  93. 93.

    Galler K, Fröhlich E, Kortgen A, Bauer M, Popp J, Neugebauer U. Hepatic cirrhosis and recovery as reflected by Raman spectroscopy: information revealed by statistical analysis might lead to a prognostic biomarker. Anal Bioanal Chem. 2016;408:8053–8063.

  94. 94.

    Legesse FB, Heuke S, Galler K, Hoffmann P, Schmitt M, Neugebauer U, Bauer M, Popp J. Hepatic vitamin A content investigation using coherent anti-stokes Raman scattering microscopy. ChemPhysChem. 2016;17:4043–4051.

  95. 95.

    Neugebauer U, März A, Henkel T, Schmitt M, Popp J. Spectroscopic detection and quantification of heme and heme degradation products. Anal Bioanal Chem. 2012;404:2819–2829.

  96. 96.

    Recknagel P, Gonnert FA, Westermann M, Lambeck S, Lupp A, Rudiger A, Dyson A, Carré JE, Kortgen A, Krafft C, et al. Liver dysfunction and phosphatidylinositol-3-kinase signalling in early sepsis: experimental studies in rodent models of peritonitis. PLoS Med. 2012;9:e1001338.

  97. 97.

    Yan D, Domes C, Domes R, Frosch T, Popp J, Pletz MW, Frosch T. Fiber enhanced Raman spectroscopic analysis as a novel method for diagnosis and monitoring of diseases related to hyperbilirubinemia and hyperbiliverdinemia. Analyst. 2016;141:6104–6115.

  98. 98.

    Pichi F, Sarraf D, Arepalli S, Lowder CY, Cunningham ET, Neri P, Albini TA, Gupta V, Baynes K, Srivastava SK. The application of optical coherence tomography angiography in uveitis and inflammatory eye diseases. Prog Retin Eye Res. 2017;59:178–201. https://doi.org/10.1016/j.preteyeres.2017.04.005.

  99. 99.

    Agarwal A, Mahajan S, Khairallah M, Mahendradas P, Gupta A, Gupta V. Multimodal imaging in ocular tuberculosis. Ocul Immunol Inflamm. 2017;25:134–145.

  100. 100.

    Ward TS, Reddy AK. Fundus autofluorescence in the diagnosis and monitoring of acute retinal necrosis. J Ophthalmic Inflamm Infect. 2015;5:19.

  101. 101.

    Hosseini K, Jongsma F, Hendrikse F, Motamedi M. Non-invasive monitoring of commonly used intraocular drugs against endophthalmitis by Raman spectroscopy. Lasers Surg Med. 2003;32:265–270.

  102. 102.

    Mills B, Bradley M, Dhaliwal K. Optical imaging of bacterial infections. Clin Transl Imaging. 2016;4: 163–174.

  103. 103.

    van Oosten M, Hahn M, Crane LMA, Pleijhuis RG, Francis KP, van Dijl JM, van Dam GM. Targeted imaging of bacterial infections: advances, hurdles and hopes. FEMS Microbiol Rev. 2015;39:892–916.

  104. 104.

    Chen H, Zhang M, Li B, Chen D, Dong X, Wang Y, Gu Y. Versatile antimicrobial peptide-based ZnO quantum dots for in vivo bacteria diagnosis and treatment with high specificity. Biomaterials. 2015;53:532–544.

  105. 105.

    Chen H, Liu C, Chen D, Madrid K, Peng S, Dong X, Zhang M, Gu Y. Bacteria-targeting conjugates based on antimicrobial peptide for bacteria diagnosis and therapy. Mol Pharm. 2015;12:2505–2516.

  106. 106.

    Yang C, Ren C, Zhou J, Liu J, Zhang Y, Huang F, Ding D, Xu B, Liu J. Dual fluorescent- and isotopic-labelled self-assembling vancomycin for in vivo imaging of bacterial infections. Angew Chem Int Ed Engl. 2017;56:2356–2360.

  107. 107.

    Suri S, Lehman SM, Selvam S, Reddie K, Maity S, Murthy N, Garca AJ. In vivo fluorescence imaging of biomaterial-associated inflammation and infection in a minimally invasive manner. J Biomed Mater Res A. 2015;103:76–83.

  108. 108.

    Panizzi P, Nahrendorf M, Figueiredo JL, Panizzi J, Marinelli B, Iwamoto Y, Keliher E, Maddur AA, Waterman P, Kroh HK, Leuschner F, Aikawa E, Swirski FK, Pittet MJ, Hackeng TM, Fuentes-Prior P, Schneewind O, Bock PE, Weissleder R. In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation. Nat Med. 2011;17:1142–1146.

  109. 109.

    Akhtar MS, Khan ME, Khan B, Irfanullah J, Afzal MS, Khan MA, Nadeem MA, Jehangir M, Imran MB. An imaging analysis of (99m) tc-UBI (29-41) uptake in S. aureus infected thighs of rabbits on ciprofloxacin treatment. Eur J Nucl Med Mol Imaging. 2008;35:1056–1064.

  110. 110.

    Nibbering PH, Welling MM, Paulusma-Annema A, Brouwer CPJM, Lupetti A, Pauwels EKJ. 99Mtc-labeled ubi 29-41 peptide for monitoring the efficacy of antibacterial agents in mice infected with Staphylococcus aureus. J Nucl Med. 2004;45:321– 326.

  111. 111.

    Roncali E, Savinaud M, Levrey O, Rogers KL, Maitrejean S, Tavitian B. New device for real-time bioluminescence imaging in moving rodents. J Biomed Opt. 2008;13:054035.

  112. 112.

    Hoshino H. Current advanced bioluminescence technology in drug discovery. Expert Opin Drug Discov. 2009; 4:373–389.

  113. 113.

    Sato A, Klaunberg B, Tolwani R. In vivo bioluminescence imaging. Comp Med. 2004;54:631–634.

  114. 114.

    Roda A, Guarigli M, Michelini E, Mirasoli M, Pasini P. Analytical bioluminescence and chemiluminescence. Anal Chem. 2003;75:463A–470A.

  115. 115.

    Roda A, Guardigli M. Analytical chemiluminescence and bioluminescence: latest achievements and new horizons. Anal Bioanal Chem. 2012;402:69–76.

  116. 116.

    Sadikot RT, Blackwell TS. Bioluminescence imaging. Proc Am Thorac Soc. 2005;2:537–40. 511–2.

  117. 117.

    Zinn KR, Chaudhuri TR, Szafran AA, O’Quinn D, Weaver C, Dugger K, Lamar D, Kesterson RA, Wang X, Frank SJ. Noninvasive bioluminescence imaging in small animals. ILAR J. 2008; 49:103–115.

  118. 118.

    Andreu N, Zelmer A, Fletcher T, Elkington PT, Ward TH, Ripoll J, Parish T, Bancroft GJ, Schaible U, Robertson BD, Wiles S. Optimisation of bioluminescent reporters for use with mycobacteria. PloS One. 2010;5:e10777.

  119. 119.

    Contag CH, Contag PR, Mullins JI, Spilman SD, Stevenson DK, Benaron DA. Photonic detection of bacterial pathogens in living hosts. Mol Microbiol. 1995;18:593–603.

  120. 120.

    Wu W, Su J, Tang C, Bai H, Ma Z, Zhang T, Yuan Z, Li Z, Zhou W, Zhang H, et al. cybluc: an effective aminoluciferin derivative for deep bioluminescence imaging. Anal Chem. 2017;89:4808–4816.

  121. 121.

    Chen Y, Xianyu Y, Wu J, Dong M, Zheng W, Sun J, Jiang X. Double-enzymes-mediated bioluminescent sensor for quantitative and ultrasensitive point-of-care testing. Anal Chem. 2017;89:5422–5427.

  122. 122.

    Kadurugamuwa JL, Modi K, Yu J, Francis KP, Purchio T, Contag PR. Noninvasive biophotonic imaging for monitoring of catheter-associated urinary tract infections and therapy in mice. Infect Immun. 2005;73: 3878–3887.

  123. 123.

    Garcez AS, Nunez SC, Lage-Marques JL, Hamblin MR, Ribeiro MS. Photonic real-time monitoring of bacterial reduction in root canals by genetically engineered bacteria after chemomechanical endodontic therapy. Braz Dent J. 2007;18:202–207.

  124. 124.

    Je HJ, Kim MG, Kwon HJ. Bioluminescence assays for monitoring chondrogenic differentiation and cartilage regeneration. Sensors. 2017;7(6):E1306. https://doi.org/10.3390/s17061306.

  125. 125.

    Hamblin MR, Zahra T, Contag CH, McManus AT, Hasan T. Optical monitoring and treatment of potentially lethal wound infections in vivo. J Infect Dis. 2003;187:1717–1726.

  126. 126.

    Fila G, Kasimova K, Arenas Y, Nakonieczna J, Grinholc M, Bielawski KP, Lilge L. Murine model imitating chronic wound infections for evaluation of antimicrobial photodynamic therapy efficacy. Front Microbiol. 2017;7:1258. https://doi.org/10.3389/fmicb.2016.01258.

  127. 127.

    Ragas X, Sanchez-Garcia D, Ruiz-Gonzalez R, Dai T, Agut M, Hamblin MR, Nonell S. Cationic porphycenes as potential photosensitizers for antimicrobial photodynamic therapy. J Med Chem. 2010;53: 7796–7803.

  128. 128.

    Jacobsen ID, Lüttich A, Kurzai O, Hube B, Brock M. In vivo imaging of disseminated murine Candida albicans infection reveals unexpected host sites of fungal persistence during antifungal therapy. J Antimicrob Chemother. 2014;69:2785–2796.

  129. 129.

    Hsieh SH, Brunke S, Brock M. Encapsulation of antifungals in micelles protects Candida albicans during gall-bladder infection. Front Microbiol. 2017;8:117.

  130. 130.

    Brock M. Bringing light into the dark site of infection. Cytometry A. 2015;87:793–794.

  131. 131.

    Krappmann S. Lightning up the worm: How to probe fungal virulence in an alternative mini-host by bioluminescence. Virulence. 2015;6:727–729.

  132. 132.

    Andreu N, Elkington PT, Wiles S. Molecular imaging in TB: from the bench to the clinic. Understanding tuberculosis-global experiences and innovative approaches to the diagnosis., InTech; 2012. p. 307–332.

  133. 133.

    Zelmer A, Carroll P, Andreu N, Hagens K, Mahlo J, Redinger N, Robertson BD, Wiles S, Ward TH, Parish T, et al. A new in vivo model to test anti-tuberculosis drugs using fluorescence imaging. J Antimicrob Chemother. 2012;67:1948–1960.

  134. 134.

    Kong Y, Yang D, Cirillo SL, Li S, Akin A, Francis KP, Maloney T, Cirillo JD. Application of fluorescent protein expressing strains to evaluation of anti-tuberculosis therapeutic efficacy in vitro and in vivo. PloS One. 2016;11:e0149972.

  135. 135.

    Andreu N, Zelmer A, Sampson SL, Ikeh M, Bancroft GJ, Schaible UE, Wiles S, Robertson BD. Rapid in vivo assessment of drug efficacy against mycobacterium tuberculosis using an improved firefly luciferase. J Antimicrob Chemother. 2013;68:2118–2127.

  136. 136.

    Kong Y, Yao H, Ren H, Subbian S, Cirillo SLG, Sacchettini JC, Rao J, Cirillo JD. Imaging tuberculosis with endogenous beta-lactamase reporter enzyme fluorescence in live mice. Proc Natl Acad Sci USA. 2010;107:12239–12244.

  137. 137.

    DaCosta RS, Kulbatski I, Lindvere-Teene L, Starr D, Blackmore K, Silver JI, Opoku J, Wu YC, Medeiros PJ, Xu W, et al. Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: first-in-human results. PLoS One. 2015;10:e0116623.

  138. 138.

    Wu YC, Smith M, Chu A, Lindvere-Teene L, Starr D, Tapang K, Shekhman R, Wong O, Linden R, DaCosta RS. Handheld fluorescence imaging device detects subclinical wound infection in an asymptomatic patient with chronic diabetic foot ulcer: a case report. Int Wound J. 2016;13:449–453.

  139. 139.

    Ottolino-Perry K, Chamma E, Blackmore KM, Lindvere-Teene L, Starr D, Tapang K, Rosen CF, Pitcher B, Panzarella T, Linden R, et al. Improved detection of clinically relevant wound bacteria using autofluorescence image-guided sampling in diabetic foot ulcers. Int Wound J. 2017;14(5):833–841. https://doi.org/10.1111/iwj.12717.

  140. 140.

    Keenan JB, Rajab TK, Armstrong DG, Khalpey Z. Real-time autofluorescence imaging to diagnose lvad driveline infections. Ann Thorac Surg. 2017;103:e493–e495.

  141. 141.

    Yin R, Dai T, Avci P, Jorge AES, de Melo WCMA, Vecchio D, Huang YY, Gupta A, Hamblin MR. Light-based anti-infectives: ultraviolet C irradiation, photodynamic therapy, blue light, and beyond. Curr Opin Pharmacol. 2013;13:731–762.

  142. 142.

    Celli JP, Spring BQ, Rizvi I, Evans CL, Samkoe KS, Verma S, Pogue BW, Hasan T. Imaging and photodynamic therapy: Mechanisms, monitoring, and optimization. Chem Rev. 2010;110:2795–2838.

  143. 143.

    Galstyan A, Block D, Niemann S, Grner MC, Abbruzzetti S, Oneto M, Daniliuc CG, Hermann S, Viappiani C, Schfers M, Lffler B, Strassert CA, Faust A. Labeling and selective inactivation of Gram-positive bacteria employing bimodal photoprobes with dual readouts. Chemistry. 2016; 22:5243–5252.

  144. 144.

    Xing B, Jiang T, Bi W, Yang Y, Li L, Ma M, Chang CK, Xu B, Yeow EKL. Multifunctional divalent vancomycin: the fluorescent imaging and photodynamic antimicrobial properties for drug resistant bacteria. Chem Commun. 2011;47:1601–1603.

  145. 145.

    Dai T, Tegos GP, Zhiyentayev T, Mylonakis E, Hamblin MR. Photodynamic therapy for methicillin-resistant Staphylococcus aureus infection in a mouse skin abrasion model. Lasers Surg Med. 2010;42:38–44.

  146. 146.

    Shao Q, Xing B. Enzyme responsive luminescent ruthenium(II) cephalosporin probe for intracellular imaging and photoinactivation of antibiotics resistant bacteria. Chem Commun (Camb). 2012;48:1739–1741.

  147. 147.

    O’Riordan K, Akilov OE, Chang SK, Foley JW, Hasan T. Real-time fluorescence monitoring of phenothiazinium photosensitizers and their anti-mycobacterial photodynamic activity against Mycobacterium bovis BCG in in vitro and in vivo models of localized infection. Photochem Photobiol Sci. 2007;6:1117–1123.

  148. 148.

    Stöckel S, Kirchhoff J, Neugebauer U, Rösch P, Popp J. The application of Raman spectroscopy for the detection and identification of microorganisms. J Raman Spectrosc. 2016;47:89–109.

  149. 149.

    Krafft C, Popp J. The many facets of Raman spectroscopy for biomedical analysis. Anal Bioanal Chem. 2015;407:699–717.

  150. 150.

    Neugebauer U, Rösch P, Popp J. Raman spectroscopy towards clinical application: drug monitoring and pathogen identification. Int J Antimicrob Agents. 2015;46:S35–S39.

  151. 151.

    Schröder UC, Ramoji A, Glaser U, Sachse S, Leiterer C, Csaki A, Hübner U, Fritzsche W, Pfister W, Bauer M, et al. Combined dielectrophoresis–Raman setup for the classification of pathogens recovered from the urinary tract. Anal Chem. 2013;85:10717–10724.

  152. 152.

    Kloß S, Lorenz B, Dees S, Labugger I, Rösch P, Popp J. Destruction-free procedure for the isolation of bacteria from sputum samples for Raman spectroscopic analysis. Anal Bioanal Chem. 2015;407:8333–8341.

  153. 153.

    Kloß S, Rosch P, Pfister W, Kiehntopf M, Popp J. Toward culture-free Raman spectroscopic identification of pathogens in ascitic fluid. Anal Chem. 2015;87:937–943.

  154. 154.

    Walter A, Schumacher W, Bocklitz T, Reinicke M, Rösch P, Kothe E, Popp J. From bulk to single-cell classification of the filamentous growing Streptomyces bacteria by means of Raman spectroscopy. Appl Spectrosc. 2011;65:1116–1125.

  155. 155.

    Kloß S, Kampe B, Sachse S, Rosch P, Straube E, Pfister W, Kiehntopf M, Popp J. Culture-independent Raman spectroscopic identification of urinary tract infection pathogens: a proof of principle study. Anal Chem. 2013;85:9610–9616.

  156. 156.

    Münchberg U, Rösch P, Bauer M, Popp J. Raman spectroscopic identification of single bacterial cells under antibiotic influence. Anal Bioanal Chem. 2014;406:3041–3050.

  157. 157.

    Stöckel S, Stanca AS, Helbig J, Rösch P, Popp J. Raman spectroscopic monitoring of the growth of pigmented and non-pigmented mycobacteria. Anal Bioanl Chem. 2015;407:8919–8923.

  158. 158.

    Große C, Bergner N, Dellith J, Heller R, Bauer M, Mellmann A, Popp J, Neugebauer U. Label-free imaging and spectroscopic analysis of intracellular bacterial infections. Anal Chem. 2015;87:2137–2142.

  159. 159.

    Brückner M, Becker K, Popp J, Frosch T. Fiber array-based hyperspectral Raman imaging for chemical selective analysis of malaria-infected red blood cells. Anal Chim Acta. 2015;894:76–84.

  160. 160.

    Neugebauer U, Trenkmann S, Bocklitz T, Schmerler D, Kiehntopf M, Popp J. Fast differentiation of SIRS and sepsis from blood plasma of ICU patients using Raman spectroscopy. J Biophotonics. 2014;7:232–240.

  161. 161.

    Schmit V, Martoglio R, Carron K. Lab-on-a-bubble surface enhanced Raman indirect immunoassay for cholera. Anal Chem. 2012;84:4233–4236.

  162. 162.

    Ellis DI, Goodacre R. Metabolic fingerprinting in disease diagnosis: biomedical applications of infrared and Raman spectroscopy. Analyst. 2006;131:875–885.

  163. 163.

    Wang L, Mizaikoff B. Application of multivariate data-analysis techniques to biomedical diagnostics based on mid-infrared spectroscopy. Anal Bioanal Chem. 2008;391:1641–1654.

  164. 164.

    Clemens G, Hands JR, Dorling KM, Baker MJ. Vibrational spectroscopic methods for cytology and cellular research. Analyst. 2014;139:4411–4444.

  165. 165.

    Didonna A, Vaccari L, Bek A, Legname G. Infrared microspectroscopy: a multiple-screening platform for investigating single-cell biochemical perturbations upon prion infection. ACS Chem Neurosci. 2011;2:160–174.

  166. 166.

    Assmann C, Kirchhoff J, Beleites C, Hey J, Kostudis S, Pfister W, Schlattmann P, Popp J, Neugebauer U. Identification of vancomycin interaction with Enterococcus faecalis within 30 min of interaction time using Raman spectroscopy. Anal Bioanal Chem. 2015;407:8343–8352.

  167. 167.

    Schröder U C, Beleites C, Assmann C, Glaser U, Hübner U, Pfister W, Fritzsche W, Popp J, Neugebauer U. Detection of vancomycin resistances in enterococci within 3 1/2 hours. Sci Rep. 2015;5:8217. https://doi.org/10.1038/srep08217.

  168. 168.

    Schröder UC, Kirchhoff J, Hübner U, Mayer G, Glaser U, Henkel T, Pfister W, Fritzsche W, Popp J, Neugebauer U. On-chip spectroscopic assessment of microbial susceptibility to antibiotics within 3.5 hours. J Biophotonics. 2017;10(11):1547–1557. https://doi.org/10.1002/jbio.201600316.

  169. 169.

    Sharaha U, Rodriguez-Diaz E, Riesenberg K, Bigio IJ, Huleihel M, Salman A. Using infrared spectroscopy and multivariate analysis to detect antibiotics’ resistant Escherichia coli bacteria. Anal Chem. 2017;89 (17):8782–8790. https://doi.org/10.1021/acs.analchem.7b01025.

  170. 170.

    Dong T, Zhao X. Rapid identification and susceptibility testing of uropathogenic microbes via immunosorbent ATP-bioluminescence assay on a microfluidic simulator for antibiotic therapy. Anal Chem. 2015;87:2410–2418.

  171. 171.

    Cushnie TPT, O’Driscoll NH, Lamb AJ. Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action. Cell Mol Life Sci. 2016;73:4471–4492.

  172. 172.

    Choi J, Yoo J, Lee M, Kim EG, Lee JS, Lee S, Joo S, Song SH, Kim EC, Lee JC, Kim HC, Jung YG, Kwon S. A rapid antimicrobial susceptibility test based on single-cell morphological analysis. Sci Transl Med. 2014;6:267ra174.

  173. 173.

    Begg EJ, Barclay ML, Kirkpatrick CM. The therapeutic monitoring of antimicrobial agents. Br J Clin Pharmacol. 2001;52:35–43.

  174. 174.

    Ashbee HR, Barnes RA, Johnson EM, Richardson MD, Gorton R, Hope WW. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother. 2013;69:1162–1176.

  175. 175.

    El-Najjar N, Jantsch J, Gessner A. The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients. Clin Chem Lab Med. 2017;55(9):1246–1261. https://doi.org/10.1515/cclm-2016-0700.

  176. 176.

    Ge L, Yu J. Drug monitoring: bright lights yield drug readout. Nat Chem Biol. 2014;10:490–491.

  177. 177.

    Rong G, Corrie SR, Clark HA. In vivo biosensing: progress and perspectives. ACS Sensors. 2017;2: 327–338.

  178. 178.

    Berger AG, Restaino SM, White IM. Vertical-flow paper SERS system for therapeutic drug monitoring of flucytosine in serum. Anal Chim Acta. 2017;949:59–66.

  179. 179.

    Zengin A, Tamer U, Caykara T. Extremely sensitive sandwich assay of kanamycin using surface-enhanced Raman scattering of 2-mercaptobenzothiazole labeled gold@silver nanoparticles. Anal Chim Acta. 2014;817:33–41.

  180. 180.

    Hidi I, Mühlig A, Jahn M, Liebold F, Cialla D, Weber K, Popp J. LOC-SERS: towards point-of-care diagnostic of methotrexate. Anal Methods. 2014;6:3943–3947.

  181. 181.

    Hidi I, Jahn M, Weber K, Cialla-May D, Popp J. Droplet-based microfluidics: spectroscopic characterization of levofloxacin and its SERS detection. Phys Chem Chem Phys. 2015;17:21236–21242.

  182. 182.

    Hidi IJ, Jahn M, Weber K, Bocklitz T, Pletz MW, Cialla-May D, Popp J. Lab-on-a-chip-surface enhanced Raman scattering combined with the standard addition method: toward the quantification of nitroxoline in spiked human urine samples. Anal Chem. 2016;88:9173–9180.

  183. 183.

    Hidi IJ, Heidler J, Weber K, Cialla-May D, Popp J. Ciprofloxacin: pH-dependent SERS signal and its detection in spiked river water using loc-SERS. Anal Bioanal Chem. 2016;408:8393–8401.

  184. 184.

    Hidi IJ, Jahn M, Pletz MW, Weber K, Cialla-May D, Popp J. Toward levofloxacin monitoring in human urine samples by employing the loc-SERS technique. J Phys Chem C. 2016;120:20613–20623.

  185. 185.

    Strelau KK, Kretschmer R, Möller R, Fritzsche W, Popp J. SERS As tool for the analysis of DNA-chips in a microfluidic platform. Anal Bioanal Chem. 2010;396:1381–1384.

  186. 186.

    Patze S, Huebner U, Liebold F, Weber K, Cialla-May D, Popp J. SERS As an analytical tool in environmental science: The detection of sulfamethoxazole in the nanomolar range by applying a microfluidic cartridge setup. Anal Chim Acta. 2017;949:1–7.

  187. 187.

    Kamińska A, Witkowska E, Kowalska A, Skoczyńska A, Gawryszewska I, Guziewicz E, Snigurenko D, Waluk J. Highly efficient SERS-based detection of cerebrospinal fluid neopterin as a diagnostic marker of bacterial infection. Anal Bioanal Chem. 2016;408:4319–4327.

  188. 188.

    Jahn IJ, Zukovskaja O, Zheng XS, Weber K, Bocklitz TW, Cialla-May D, Popp J. Surface-enhanced Raman spectroscopy and microfluidic platforms: challenges, solutions and potential applications. Analyst. 2017;142:1022–1047.

  189. 189.

    Cialla-May D, Zheng XS, Weber K, Popp J. Recent progress in surface-enhanced Raman spectroscopy for biological and biomedical applications: from cells to clinics. Chem Soc Rev. 2017;46:3945–3961.

  190. 190.

    März A, Trupp S, Rösch P, Mohr GJ, Popp J. Fluorescence dye as novel label molecule for quantitative SERS investigations of an antibiotic. Anal Bioanal Chem. 2012;402:2625–2631.

  191. 191.

    Frosch T, Yan D, Popp J. Ultrasensitive fiber enhanced UV resonance Raman sensing of drugs. Anal Chem. 2013;85:6264–6271.

  192. 192.

    Frosch T, Schmitt M, Popp J. Raman spectroscopic investigation of the antimalarial agent mefloquine. Anal Bioanal Chem. 2007;387:1749–1757.

  193. 193.

    Yan D, Popp J, Pletz MW, Frosch T. Highly sensitive broadband Raman sensing of antibiotics in step-index hollow-core photonic crystal fibers. Acs Photonics. 2017;4:138–145.

  194. 194.

    Cappi G, Spiga FM, Moncada Y, Ferretti A, Beyeler M, Bianchessi M, Decosterd L, Buclin T, Guiducci C. Label-freedetection of tobramycin in serum by transmission-localized surface plasmon resonance. Anal Chem. 2015;87:5278–5285.

  195. 195.

    Losoya-Leal A, Estevez MC, Martínez-chapa SO, Lechuga LM. Design of a surface plasmon resonance immunoassay for therapeutic drug monitoring of amikacin. Talanta. 2015;141:253–258.

  196. 196.

    McKeating KS, Aubé A, Masson JF. Biosensors and nanobiosensors for therapeutic drug and response monitoring. Analyst. 2016;141:429–449.

  197. 197.

    Griss R, Schena A, Reymond L, Patiny L, Werner D, Tinberg CE, Baker D, Johnsson K. Bioluminescent sensor proteins for point-of-care therapeutic drug monitoring. Nat Chem Biol. 2014;10:598–603.

  198. 198.

    Cash KJ, Li C, Xia J, Wang LV, Clark HA. Optical drug monitoring: photoacoustic imaging of nanosensors to monitor therapeutic lithium in vivo. ACS nano. 2015;9:1692–1698.

  199. 199.

    Ranamukhaarachchi SA, Padeste C, Dübner M, Häfeli UO, Stoeber B, Cadarso VJ. Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes. Sci Rep. 2016;6:29075.

  200. 200.

    McKeating KS, Couture M, Dinel MP, Garneau-Tsodikova S, Masson JF. High-throughput LSPR and SERS analysis of aminoglycoside antibiotics. Analyst 2016;141:5120–5126.

  201. 201.

    Wang X, Zou M, Xu X, Lei R, Li K, Li N. Determination of human urinary kanamycin in one step using urea-enhanced surface plasmon resonance light-scattering of gold nanoparticles. Anal Bioanal Chem. 2009; 395:2397–2403.

  202. 202.

    Mamián-López MB, Poppi RJ. Quantification of moxifloxacin in urine using surface-enhanced Raman spectroscopy (SERS) and multivariate curve resolution on a nanostructured gold surface. Anal Bioanal Chem. 2013; 405:7671.

  203. 203.

    Liu D, Luo P, Sun W, Zhang L, Wang Z. Detection of β-glucans using an amperometric biosensor based on high-affinity interaction between dectin-1 and β-glucans. Anal Biochem. 2010;404:14–20.

  204. 204.

    Zou C, Wu B, Dong Y, Song Z, Zhao Y, Ni X, Yang Y, Liu Z. Biomedical photoacoustics: fundamentals, instrumentation and perspectives on nanomedicine. Int J Nanomedicine. 2017;12:179–195.

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Financial support by the BMBF via the Integrated Research and Treatment Center “Center for Sepsis Control and Care” (CSCC, FKZ 01EO1502) and via the Forschungscampus InfectoGnostics (FKZ 13GW0096F), the DFG via the research group FOR 1738 “Heme and heme degradation products” and via the Core Facility Jena Biophotonic and Imaging Laboratory (JBIL, FKZ: PO 633/29-1, BA 1601/10-1), as well as the European Union via HemoSpec (FP7-ICT-2013-CN-611682) and the Leibniz Society via the Leibniz ScienceCampus InfectoOptics (SAS-2015-HKI-LWC) is highly acknowledged.

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Published in the topical collection celebrating ABCs 16th Anniversary.

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Tannert, A., Ramoji, A., Neugebauer, U. et al. Photonic monitoring of treatment during infection and sepsis: development of new detection strategies and potential clinical applications. Anal Bioanal Chem 410, 773–790 (2018). https://doi.org/10.1007/s00216-017-0713-z

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  • Treatment response
  • Microcirculation imaging
  • Therapeutic drug monitoring
  • Indocyanine clearance
  • Imaging infection
  • Antibiotic susceptibility testing