Abstract
The field of precision medicine—the possibility to accurately tailor pharmacological treatments to each specific patient—would be significantly advanced by the ability to rapidly, conveniently, and cost-effectively measure biomarkers directly at the point of care. Electrochemical aptamer-based (E-AB) sensors appear a promising approach to this end due to their low cost, ease of use, and good analytical performance in complex clinical samples. Thus motivated, we present here the development of an E-AB sensor for the measurement of the amino acid l-tryptophan, a diagnostic marker indicative of a number of metabolic and mental health disorders, in urine. The sensor employs a previously reported DNA aptamer able to recognize the complex formed between tryptophan and a rhodium-based receptor. We adopted the aptamer to the E-AB sensing platform by truncating it, causing it to undergo a binding-induced conformational change, modifying it with a redox-reporting methylene blue, and attaching it to an interrogating electrode. The resulting sensor is able to measure tryptophan concentrations in the micromolar range in minutes and readily discriminates between its target and other aromatic and non-aromatic amino acids. Using it, we demonstrate the measurement of clinically relevant tryptophan levels in synthetic urine in a process requiring only a single dilution step. The speed and convenience with which this is achieved suggest that the E-AB platform could significantly improve the ease and frequency with which metabolic diseases are monitored.
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References
Schork NJ. Personalized medicine: time for one-person trials. Nature. 2015;520:609–11.
Ahmed MU, Saaem I, Wu PC, Brown AS. Personalized diagnostics and biosensors: a review of the biology and technology needed for personalized medicine. Crit Rev Biotechnol. 2014;34:180–96.
Nayak S, Blumenfeld NR, Laksanasopin T, Sia SK. Point-of-care diagnostics: recent developments in a connected age. Anal Chem. 2016;89:102–23.
Hoedemaekers CW, Gunnewiek JMK, Prinsen MA, Willems JL, Van der Hoeven JG. Accuracy of bedside glucose measurement from three glucometers in critically ill patients. Crit Care Med. 2008;36:3062–6.
Solnica B, Naskalski JW, Sieradzki J. Analytical performance of glucometers used for routine glucose self-monitoring of diabetic patients. Clin Chim Acta. 2003;331:29–35.
Clarke SF, Foster JR. A history of blood glucose meters and their role in self-monitoring of diabetes mellitus. Bri J Biomed Sci. 2012;69:83–93.
Lubin AA, Plaxco KW. Folding-based electrochemical biosensors: the case for responsive nucleic acid architectures. Acc Chem Res. 2010;43:496–505.
Schoukroun-Barnes LR, Macazo FC, Gutierrez B, Lottermoser J, Liu J, White RJ. Reagentless, structure-switching, electrochemical aptamer-based sensors. Annu Rev Anal Chem. 2016;9:163–81.
Xiao Y, Lubin AA, Heeger AJ, Plaxco KW. Label-free electronic detection of thrombin in blood serum by using an aptamer-based sensor. Angew Chem. 2005;117:5592–5.
Lai RY, Plaxco KW, Heeger AJ. Aptamer-based electrochemical detection of picomolar platelet-derived growth factor directly in blood serum. Anal Chem. 2007;79:229–33.
Rowe AA, Miller EA, Plaxco KW. Reagentless measurement of aminoglycoside antibiotics in blood serum via an electrochemical, ribonucleic acid aptamer-based biosensor. Anal Chem. 2010;82:7090–5.
Baker BR, Lai RY, Wood MS, Doctor EH, Heeger AJ, Plaxco KW. An electronic, aptamer-based small-molecule sensor for the rapid, label-free detection of cocaine in adulterated samples and biological fluids. J Am Chem Soc. 2006;128:3138–9.
Palego L, Betti L, Rossi A, Giannaccini G. Tryptophan biochemistry: structural, nutritional, metabolic, and medical aspects in humans. J Amino Acids. 2016;2016:13.
Kałużna-Czaplińska J, Gątarek P, Chirumboloalvatore, Chartrand MS, Bjørklund G (2017) How important is tryptophan in human health? Crit Rev Food Sci Nutr. https://doi.org/10.1080/10408398.2017.1357534.
Snedden W, Mellor CS, Martin JR. Familial hypertryptophanemia, tryptophanuria and indoleketonuria. Clin Chim Acta. 1983;131:247–56.
Martin JR, Mellor CS, Fraser FC. Familial hypertryptophanemia in two siblings. Clin Gen. 1995;47:180–3.
Wilcken B, Yu JS, Brown DA. Natural history of Hartnup disease. Arch Dis Child. 1977;52:38–40.
Lindseth G, Helland B, Caspers J. The effects of dietary tryptophan on affective disorders. Arch Psychiatr Nurs. 2015;29:102–7.
Kałuzna-Czaplinska J, Michalska M, Rynkowski J. Determination of tryptophan in urine of autistic and healthy children by gas chromatography/mass spectrometry. Med Sci Monit. 2010;16:CR488–92.
Camp KM, Lloyd-Puryear MA, Huntington KL. Nutritional treatment for inborn errors of metabolism: indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example. Mol Genet Metab. 2012;107:3–9.
Saudubray JM, Sedel F, Walter JH. Clinical approach to treatable inborn metabolic diseases: an introduction. J Inherit Metab Dis. 2006;29:261–74.
Yang KA, Barbu M, Halim M, Pallavi P, Kim B, Kolpashchikov DM, et al. Recognition and sensing of low-epitope targets via ternary complexes with oligonucleotides and synthetic receptors. Nat Chem. 2014;6:1003.
PUTNAM DF Composition and concentrative properties of human urine (1971) NASA Contractor Reports, p 109.
Xiao Y, Lai RY, Plaxco KW. Preparation of electrode-immobilized, redox-modified oligonucleotides for electrochemical DNA and aptamer-based sensing. Nat Protoc. 2007;2:2875.
Ricci F, Zari N, Caprio F, Recine S, Amine A, Moscone D, et al. Surface chemistry effects on the performance of an electrochemical DNA sensor. Bioelectrochemistry. 2009;76:208–13.
White RJ, Rowe AA, Plaxco KW. Re-engineering aptamers to support reagentless, self-reporting electrochemical sensors. Analyst. 2010;135:589–94.
Kang D, Ricci F, White RJ, Plaxco KW. Survey of redox-active moieties for application in multiplexed electrochemical biosensors. Anal Chem. 2016;88:10452–8.
Safavi A, Momeni S. Electrocatalytic oxidation of tryptophan at gold nanoparticle-modified carbon ionic liquid electrode. Electroanalysis. 2010;22:2848–55.
Grabowska I, Sharma N, Vasilescu A, Iancu M, Badea G, Boukherroub R, et al. Electrochemical aptamer-based biosensors for the detection of cardiac biomarkers. ACS omega. 2018;3:12010–8.
Acknowledgements
The authors wish to thank Prof. Milan Stojanovic for advice and input.
Funding
This work was funded in part by a grant from Aptatek Biosciences. The authors of this work have no financial interest in Aptakek Biosciences. This work was also funded by grant EB022015 from the National Institutes of Health.
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Published in the topical collection Young Investigators in (Bio-)Analytical Chemistry with guest editors Erin Baker, Kerstin Leopold, Francesco Ricci, and Wei Wang.
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Idili, A., Gerson, J., Parolo, C. et al. An electrochemical aptamer-based sensor for the rapid and convenient measurement of l-tryptophan. Anal Bioanal Chem 411, 4629–4635 (2019). https://doi.org/10.1007/s00216-019-01645-0
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DOI: https://doi.org/10.1007/s00216-019-01645-0