Supramolecular Wearable Sensors

Abstract

In this issue of Chem, Jang et al. report a wearable sensor device for the rapid and sensitive detection of amphetamine-type stimulants in point-of-use conditions. The device characteristics benefit from superb supramolecular analytical chemistry and make it one of the most notable examples of sensor development. In this issue of Chem, Jang et al. report a wearable sensor device for the rapid and sensitive detection of amphetamine-type stimulants in point-of-use conditions. The device characteristics benefit from superb supramolecular analytical chemistry and make it one of the most notable examples of sensor development. Wearables are small electronic devices (often consisting of one or more sensors) that play an increasingly dominant role in our modern society. Wireless, wearable devices have a large societal impact. They track and respond to our emotions, enable effortless communication, compute and urge changes in our lifestyle and fitness, support our healthcare monitoring, analyzing, and even healing abilities, and encompass the many wearable technology applications that were unthinkable less than a decade ago. Smart, wearable devices that assist in drug detection under point-of-use conditions are urgently needed to address the negative side effects of drug use and detect drug abuse. As a case in point, devices detecting amphetamine-type stimulants (ATSs) would assist physicians and patients to carefully tune doses of ATSs in the treatment of, e.g., attention deficit hyperactivity disorder, narcolepsy, asthma, and depression and in the prevention of side effects of ATSs, such as insomnia, hallucination, delusions, mental illness, and violent tendencies. Importantly, these side effects have also increased the prevalence of ATS drug addiction, which represents a large societal problem for which ATS detection is needed. Evidently, wearable devices with short operation times, no requirement for trained personnel, and on-site detection are in high demand. In this issue of Chem, Jang et al. report an easy, sensitive, rapid, cheap, and portable device that detects ATSs amperometrically by synergistically combining the selectivity of supramolecular analytical chemistry and the sensitivity of organic field-effect transistors (OFETs).1Jang Y. Jang M. Kim H. Lee S.J. Jin E. Koo J.Y. Hwang I.-C. Kim Y. Ko Y.K. Hwang I. et al.Chem. 2017; 3: 641-651Abstract Full Text Full Text PDF Scopus (67) Google Scholar Sensors based on OFET platforms show great promise for use in chemical and biological sensors because of their many advantages, including high sensitivity, ultra-low cost, simple methods of fabrication, and their potential to be included in flexible devices. In particular, OFET-type sensors can amplify electrical signals obtained from binding events with analytes by tuning the applied gate voltage, leading to higher sensitivity than of conventional amperometric sensors. However, pristine OFET-based sensors without additional surface functionalization often exhibit low selectivity for target analytes because common samples such as sputum, blood, or urine contain compounds such as small molecules, DNA, and proteins, all of which can impair selectivity and sensitivity. Therefore, highly selective detection with OFET-based sensors requires chemical modification or immobilization of specific receptors to capture target analytes on a sensor's surface.2Lee M.Y. Kim H.J. Jung G.Y. Han A.R. Kwak S.K. Kim B.J. Oh J.H. Adv. Mater. 2015; 27: 1540-1546Crossref PubMed Scopus (54) Google Scholar In supramolecular chemistry, host-guest chemistry describes complexes that are composed of two or more compounds that are held together in unique structural relationships by forces other than those of full covalent bonds. Host-guest chemistry encompasses the idea of molecular recognition and interactions through noncovalent bonding. Kim and co-workers have an impressive record in the design and characterization of molecules that are recognized by synthetic hosts, particularly by employing cucurbituril-based macrocycles.3Lee J.W. Samal S. Selvapalam N. Kim H.-J. Kim K. Acc. Chem. Res. 2003; 36: 621-630Crossref PubMed Scopus (1658) Google Scholar Given their resemblance to pumpkins, which belong to the Cucurbitaceae family, cucurbiturils have received recent attention for their contribution to self-assembly via the formation of dynamic complexes with a variety of chemical species. Research efforts by the cucurbit[n]uril community continue to be directed toward identifying and characterizing suitable guest molecules, and existing ones are now tabulated in a recent review.4Barrow S.J. Kasera S. Rowland M.J. del Barrio J. Scherman O.A. Chem. Rev. 2015; 115: 12320-12406Crossref PubMed Scopus (1178) Google Scholar In this issue of Chem, Jang et al. report the formation of a stable 1:1 inclusion complex between an ATS and cucurbit[7]uril (abbreviated as CB[7] for the seven glycoluril building blocks that constitute the macrocycle), which was determined by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. All signals of the 1:1 inclusion complex were assigned by 2D NMR experiments, such as correlation spectroscopy and rotating frame Overhauser effect spectroscopy. In addition, quantitative measurements of the binding affinities between CB[7] and ATSs were performed by isothermal titration calorimetry and revealed that CB[7] had high affinities (Ka ∼ 106 M−1) for ATSs with a 1:1 binding stoichiometry. The formation of the inclusion complex was driven by enthalpy, and the large favorable enthalpic gain apparently compensated for the unfavorable entropic contribution. The enthalpic gain was a result of the hydrophobic interactions between the phenyl ring of the guest and the inner wall of the host cavity, as well as strong ion-dipole interactions between ammonium groups of the ATSs and carbonyl-laced portals of the host. Stable formation of the inclusion complex was nicely confirmed by single-crystal X-ray analyses. To take advantage of the unique recognition properties of CB[7] toward ATSs on the OFET platform, Jang et al. synthesized clever CB[7] derivatives with allyloxy side groups that enabled the incorporation of CB[7] into the OFET platforms. The side groups on the outer wall of CB[7] were introduced for solvent processability and orthogonality to the water-insoluble semiconductor layer, whereas the recognition properties of the CB[7] derivatives remained essentially the same as CB[7] itself. CB[7]-covered semiconductor layers were uniform and complete, crucial for high-sensitive sensors. Furthermore, they exhibited high on/off current ratios of more than 105 under ambient conditions and stable field-effect characteristics within the linear regime of operation, crucial for achieving signal amplification and fast response under sensing conditions. CB[7]-covered OFET sensors showed stable and linear responses for buffered and water solutions of ATSs (1 pM to 1 μM), and the detection limit was in the range of less than 1 pM. None of these signals were detected when CB[7] was absent or blocked. Notably, the authors also observed stable sensing of ATSs when operating the OFET platform with real urine samples. However, a reduced sensitivity (1 nM) was observed, probably as a result of interfering ions and various metabolites present in urine samples. These results show that the CB[7]-based OFET platform can be used for ATS detection in urine and, therefore, in real-life point-of-use settings. In a final series of experiments, the authors fabricated flexible drug sensors by using an indium-tin-oxide-coated polyethylene naphthalate flexible foil as substrate and a transparent aluminum oxide transparent gate dielectric; a schematic of the fabricated flexible sensor is shown in Figure 1. The digitized sensing current could be transmitted to an Android application via wireless Bluetooth communication, which can potentially be used in bracelet-type wearable OFET sensors. In conclusion, the fabrication of supramolecular wearable biological sensors opens an avenue for replacing not only current drug-detection methods but also biomarker-detection methods. Future work should shed light on the field testing of this type of supramolecular wearable sensor worn on the body, but additional fundamental work can also be undertaken for the development of multiplexed sensing devices that employ OFETs for protein-biomarker detection,5de Vink P.J. Briels J.M. Schrader T. Milroy L.-G. Brunsveld L. Ottmann C. Angew. Chem. Int. Ed. 2017; 56: 8998-9002Crossref PubMed Scopus (62) Google Scholar bacterial sensing,6Sankaran S. Kiren M.C. Jonkheijm P. ACS Nano. 2015; 9: 3579-3586Crossref PubMed Scopus (44) Google Scholar and cell-fate detection.7An Q. Brinkmann J. Huskens J. Krabbenborg S. de Boer J. Jonkheijm P. Angew. Chem. Int. Ed. 2012; 51: 12233-12237Crossref PubMed Scopus (108) Google Scholar Point-of-Use Detection of Amphetamine-Type Stimulants with Host-Molecule-Functionalized Organic TransistorsJang et al.ChemSeptember 28, 2017In BriefAbuse of amphetamine-type stimulants (ATS) is of increasing concern in many countries. Therefore, there is a large demand for the development of easy, fast, and cheap ATS detection methods. In this regard, we have developed a point-of-use, portable, wireless drug sensor with unprecedentedly high sensitivity toward ATS using a drug-specific host molecule, cucurbit[7]uril, and organic field-effect transistors. This work provides a viable methodology for the fabrication of highly sensitive and selective drug sensors. Full-Text PDF Open Archive