Liquid crystals-based sensor for the detection of lithocholic acid coupled with competitive host-guest inclusion
Hui Maa, Qi Kangb, Tao Wangc, Jianhong Xiaoc, Li Yua,⁎
Keywords:
Liquid crystals
Sodium dodecyl sulphate Lithocholic acid
β-Cyclodextrin
Host-guest interaction
A B S T R A C T
A simple, low-cost and label-free strategy for detecting lithocholic acid (LCA) was designed at the liquid crystals (LCs)/aqueous interface via competitive host-guest inclusion. In this method, sodium dodecyl sulfate (SDS) was initially adsorbed on the fluid interface and induced LCs to adopt the homeotropic ordering. Inclusion com- plexation of SDS and β-cyclodextrin (β-CD) disturbed interaction between LCs and SDS and evoked LCs to keep a tilted alignment. When injecting LCA into the miXed solution of SDS and β-CD, SDS excluded from the cavity of β-CD by competitive host-guest inclusion and could be re-adsorbed at the LCs/aqueous interface, resulting in the orientational transition of LCs from tilted to homeotropic state. Correspondingly, a bright-to-dark optical re- sponse was observed under polarized optical microscope (POM). The as-prepared LCs-based sensor could detect LCA as low as about 2 μM in aqueous solution. Moreover, the practicability of the approach was validated by monitoring the known amount of LCA in human urine. This work offers an appealing approach for the detection of LCA which has a great potentiality in clinical diagnosis.
1. Introduction
Lithocholic acid (LCA), a secondary bile acid generating from the 7α-dehydroXylation of chenodeoXycholic acid, is known to be a toXic endobiotics [1,2]. Elevated level of LCA makes a significant contribu- tion to carcinogenesis process [3,4]. Colon cancer is attributed to the accumulation of LCA reabsorbed poorly into enterohepatic circulation in the colon [5–7]. LCA concentration of 5 to 10 μM is also found in patients who suffer from chronic cholestatic liver disease [8]. There- fore, the establishment of LCA assay method provides useful clinical information for the diagnosis of relevant disease. However, just a few analytical methods were employed to achieve the determination of LCA, such as chromatography-mass spectrometry colorimetry [8,9] and fluorometry [10]. Although these existing methods can identify LCA with high sensitivity, they encounter some drawbacks, e.g. costly in- strumentations, complex operation procedures and electric power, etc. Therefore, there is still a challenge to develop a novel, convenient and cost-effective strategy for determination of LCA. β-CD is a cylinder-shaped host molecule with seven glucose subunits connected by α-(1, 4) glycosidic linkages [11,12]. The hydrophobic cavity of β-CD endows it with special capacity to form host-guest in- clusion complexes with a variety of suitably-sized substrates in aqueous medium. As reported previously, LCA and β-CD could form inclusion complex [10,13], which exhibited much stronger affinity to the binding sites than other complexes formed by surfactants (e.g. SDS, DTAB) and β-CD. Hence, we attempted to construct an analytical platform for LCA detection on account of a competitive host-guest complexation.
LCs were considered as responsive materials. Some pioneering work of Abbot’s group has successfully demonstrated the LCs are very sen- sitive to the presence of surfactants [14,15]. The adsorption of proteins [16,17], lipids [18,19], DNA [20–22] and polymers [23,24] at the LCs/ aqueous interface also trigger the orientational transition of LCs, which are concomitantly transduced into alteration in the measurable optical signals. Brake et al. were the first to propose the use of LCs for reporting biological binding events [25]. Recent studies have reported that LCs can also respond to fundamental interactions between antibody-antigen [26–28], surfactant-protein [29,30] and host-guest [31–33], etc. Herein a convenient, inexpensive and label-free LCs-based sensor was developed to detect LCA associated with competitive host-guest inclusion interactions. The adsorption of SDS at the LCs/aqueous in- terface was prevented due to its inclusion into β-CD. LCA could pre- dominate SDS to enter into the cavity of β-CD. As a result, the extruded SDS from the cavity of β-CD was laden at the interface and induced LCs to undergo a tilted-to-homeotropic ordering transition, corresponding to a bright to dark shift in the optical images. Based on this mechanism, the detection limit of LCA is ∼2 μM. The LCs sensor could also be used to identify LCA in human urine. This work opens a potential route for detection of LCA in practical application. Nematic liquid crystal, 4- cyano-4-pentylbi-phenyl (5CB), was utilized as LCs material. The che- mical structures of main compounds employed are shown in Fig. S1.
2. Experimental
2.1. Materials
Octyltrichlorosilane (OTS, 95%), 5CB (99%), D-(+)-glucose (ACS Grade), L-ascorbic acid (99%), potassium carbonate (K2CO3, ≥99.5%), urea (99%) and uric acid (98%) were purchased from J&K Scientific Co., Ltd. SDS (99%) was provided by Alfa Aesar (China) chemicals Co.,Ltd. β-CD (96%) was obtained from Aladdin Chemistry Co., Ltd. of China. Sodium hydroXide (NaOH, ≥96.0%) and sodium chloride (NaCl, ≥99.5%) were provided by Sinopharm Chemical Reagent Co., Ltd. LCA (> 98.0%) was produced by Tokyo Chemical Industry Co., Ltd. was dissolved in aqueous solutions at ∼pH 8 (adjusted with NaOH aqueous solution). Sodium dihydrogen phosphate dihydrate (NaH2PO4·2H2O, ≥99.0%) and disodium hydrogen phosphate dodecahydrate (Na2HPO4·12H2O, ≥99.0%) were obtained from Tianjin Damao Chemical Reagent Company of China. Copper grids were bought from Zhongjingkeyi Technology Co., Ltd of China. All the chemicals were used without further purification. Ultrapure water (18.25 MΩ cm) was obtained with the Ulupure system and used in all the experiments.
2.2. Preparation of glass microscope slides
According to previous literature [34–36], glass microscope slides were cleaned in “piranha solution” (70% H2SO4/30% H2O2) for 30 min
at 80 ℃ (Warning: do not store the lotion in closed containers; should be operated with extreme caution). After sequential rinsing with water, ethanol, and methanol, the slides were dried under inert atmosphere with N2 and stoved overnight at 110 ℃. Then clean glass slides were soaked in the solution of heptane containing OTS for 30 min, followed by rinsing the slides using methylene chloride and drying under N2.
2.3. Fabrication of LC cells
Copper specimen grids were placed onto the OTS-coated glass substrates. Initially 5CB was heated to isotropic phase (> 35 ℃) and then dispensed onto the grid. Capillary tube (20 μL) was employed to remove the excess LC to form a uniform thin film. Next, the 50 μL sample was introduced into the optical cell at ∼25 ℃. Each assay was operated at least three times.
2.4. Optical observation of LCs appearances
The optical images of these samples were captured with POM (XPF- 800C, Tianxing, Shanghai, China). Each image was obtained by a 2.5×
objective lens and a digital camera (TK-9301EC, JVC, Japan) at room temperature. The bright area coverage ratio (Br) of the optical ap- pearance was obtained by employing the Adobe Photoshop CS 6 via calculating the piXel percentage in the bright area to the total LC region. Br of the complete bright or dark was designated as 1 or 0, respectively.
2.5. Preparation of SDS/β-CD complex
SDS/β-CD complex was prepared according to the method pre- viously reported [32]. Briefly, SDS aqueous solution with a fiXed con- centration was added to different concentrations of β-CD aqueous so- lutions with equal volume at room temperature. The miXture was continuously stirred for 5 h at 45 ℃ and then cooled to room tem- perature and sonicated for 12 h.
2.6. Source and treatment method of urine
Urine samples were carefully taken from healthy individuals over a 24 h period and stored at 4 ℃. Since there is no or infinitesimal LCA existing in the urine of healthy subjects [37], known amounts of LCA were added to the urine samples to simulate the urine of patients who suffer from cholestasis.
2.7. Surface tension
Surface tension measurements were performed on model Sigma 700 force tensiometer (Biolin Scientific, Finland) to evaluate the surface activities of samples. The Wilhelmy plate method was used to de- termine the surface tension data. After every measurement, the Wilhelmy plate was completely washed and heated in the flame to re- move the residues of solutions. The surface tension values were de- termined at least five times and the mean value was considered. The thermostatic water bath was employed to control the experimental temperature.
2.8. Isothermal titration calorimetry
Isothermal titration calorimetry (ITC) was conducted on a Microcal VP-ITC apparatus with reference power of 10 μcal/s. 29 Injections of β- CD samples were added dropwise to the SDS or LCA solution. The miXture was stirred with 307 rpm at 25 ℃.
3. Results and discussion
3.1. Construction of LCs sensor based on SDS/β-CD complexes
Effect of β-CD or SDS on the alignment of LCs at the fluid interface was firstly investigated. Bright optical images of 5CB were presented when contacting with β-CD aqueous solutions in Fig. S2. There was no pronounced change observed in the optical signal with the increment of β-CD concentration, which implies that β-CD itself fails to influence the orientation of 5CB. As for SDS, bright appearance was still exhibited in the presence of lower SDS concentration (Fig. S3a–c). The orientation of LCs could turn to completely dark appearance when the concentration of SDS reached 0.25 mM or higher (Fig. S3d–f), indicative of home- otropic alignment of 5CB. These results were similar to that reported in previous work [14,31]. In consideration of the forthcoming experiment, we must ensure that the SDS concentration was not below 0.25 mM in the miXture when induced isopyknic LCA solution, because there could be no bright-to-dark transition captured under POM even though all of SDS was excluded from the cavity of β-CD. Therefore, 0.50 mM SDS after miXing with β-CD aqueous solution was selected as the optimum concentration to establish the LCs-based sensor. To evaluate the concentration of β-CD for construction of LCs-based sensor in the presence of 0.50 mM SDS, LCs textures under POM were firstly observed when 1.00 mM SDS solution was miXed with the same volume, different concentrations of β-CD aqueous solutions (0.50, 1.00, 1.60, 2.00, 3.00 and 4.00 mM). As can be seen from Fig. 1a, black op- tical image appeared in the presence of 0.25 mM β-CD. Fig. 1b–f shows that β-CD at concentration of 0.50 mM or higher in the miXture could cause the optical images of LCs to achieve the dark-to-bright shift, associated with a homeotropic-to-tilted state alteration in the alignment of LCs at the fluid interface.
In previous reports [38–40], surface tension measurements were also used to infer molecular interactions of host-guest complex. In our work, we employed surface tension technique to further ascertain the concentration of β-CD required to completely include 0.50 mM SDS in the cavities (viz. almost without free SDS). The surface tension value of 0.50 mM SDS solution was determined to be 60.12 mN m−1. In the case of β-CD aqueous solutions, the surface tension data display no change with the increasing concentration (Fig. 2, red bars), almost close to the surface tension of water. The surface tension values of SDS+β-CD miXed solutions (CSDS = 0.50 mM; Cβ-CD = 0.25, 0.50, 0.80, 1.00, 1.50, 2.00 mM) show a continuous increase at first and then reach a plateau region when the concentration of β-CD ≥ 1.00 mM (Fig. 2, blue bars). Appearance of constant surface tension values suggest that host-guest inclusion of SDS into β-CD has reached saturation when existed 1.0 mM β-CD in the SDS and β-CD miXture. That is to say, almost all of SDS were into the cavities of β-CD and no free SDS existed in solution. Combined with the results of POM, it follows that host-guest inclusion com- plexation between SDS and β-CD is responsible for the orientational transition of LCs at the fluid interface. Furthermore, the miXed solution (0.50 mM SDS, 1.00 mM β-CD) was confirmed to establish the LCs- based sensor.
3.2. Detection of LCA in aqueous solution
POM images of LCs show a bright coloring when immersed in dif- ferent concentrations of LCA aqueous solutions without SDS and β-CD
miXture (Fig. S4), which suggests that LCA itself could not influence the tilted alignment of 5CB. Afterwards, in the presence of SDS and β-CD miXture, after transferring various concentrations of LCA solutions onto the LC interface the optical signal responses were depicted in Fig. 3. Furthermore, Br of correlative LCs images was calculated by Adobe Photoshop CS 6 (Fig. 4). Obviously, bright optical images of LCs were still maintained in contact with below 2 μM LCA (Fig. 3a, b). Yet a tiny change of optical appearance was captured at CLCA =2 μM (Fig. 3c). Dark patches appeared at CLCA = 20 μM (Fig. 3d), and the black region grew bigger at CLCA = 100 μM (Fig. 3e). In the case of CLCA = 200 μM, the optical image became uniformly black within 2 h (Fig. 3f). Hence based on the above results, the LCs-based sensor could detect LCA as low as about 2 μM. In addition, we inferred that occurrence of tilted-to- homeotropic state transition for LCs alignment was due to the sub- stituent LCA for SDS. The excluded SDS molecules from the cavities of β-CD may be adsorbed again on the fluid interface, which induces 5CB to adopt the homeotropic ordering.
3.3. Detection of LCA in human urine samples
It is reported that patients suffering from cholestasis contain ele- vated levels of LCA [41]. Therefore, the content of LCA in human urine can provide significant clinical information for the diagnosis of cho- lestasis. Interfering species such as inorganic salt (NaCl, K2CO3, NaH2PO4 and Na2HPO4), glucose, ascorbic acid, urea and uric acid present in human urine may affect the detection of LCA in the sensor. Whereupon POM images of LCs incubated with SDS and β-CD miXture in the presence of 1 mM interference aqueous solutions were observed and shown in Fig. 5. Only bright optical images were observed in these aqueous solutions (Fig. 5a–h). Therefore, the LCs-based sensor enables
to monitor LCA in human urine without interference from other com- ponents in such environment. Furthermore, the sensor was applied to detect LCA in human urine samples. Various amounts of LCA were added to the urine samples. Fig. 6 shows the optical images of LCs individually observed in the absence and presence of LCA and the corresponding histogram for Br of LCs images associated with the concentrations of LCA was given in Fig. 7. Apparently, LCs displayed bright optical appearance after transferring healthy person’s urine onto the interface which incubated with the miXture of SDS and β-CD (Fig. 6a). When different con- centrations of LCA were then introduced into the sensor, the achieved experimental results (Fig. 6b–f) were similar to those in aqueous solu- tions (Fig. 3). Detection limit of the LCA was determined to be around 2 μM in human urine and closed to the lowest detection concentration of LCA aqueous solutions. These observations suggest that the LCs- based sensor could provide an access to monitor LCA in human urine, which is fascinating for the real applications.
3.4. Detection mechanisms of LCA
In view of the experimental results, we speculated that competitive host-guest complexation between host (β-CD) and guest (SDS or LCA) molecules played a crucial role in the LCs-based sensor. In order to further explore the interaction mechanism, we employed ITC to quan- titatively characterize the host-guest interaction between β-CD and SDS or LCA, respectively. The recorded titration data are shown in Fig. 8Aa and Ba for β-CD/SDS and β-CD/LCA complexes, respectively. The host- guest combination between β-CD and SDS or LCA was exothermic process and exothermic heat of the latter was much stronger than that of the former. As the injections continued, the binding of β-CD with the corresponding guest molecules gradually became saturated and the exothermic heat gradually decreased. When the β-CD was saturated with SDS or LCA, no binding occurred and only heat of dilution was observed in Fig. 8Aa and Ba. Moreover, Fig. 8Ab and Bb were sepa- rately derived from the area integral of each peak of Fig. 8Aa and Ba, which were fitted by computer simulation using the “one set of sites”
model [42]. In sharp contrast, a smooth arc-shaped isotherm for β-CD/ SDS complexation and a typical S-shape curve with an abrupt transition for β-CD/LCA host-guest pair were severally obtained. The individual association ratio (N) of β-CD to SDS or LCA was calculated to be 0.998 and 1.32, both of which is close to 1.0. The corresponding binding constant (Ka) is 1.15 × 104 M−1 and 6.28 × 105 M−1, respectively, which is separately in agreement with the association constants reported previously [43,44]. Therefore, it can be deduced that the strength of host-guest interaction between β-CD and LCA is much stronger than that of β-CD with SDS. So LCA is capable of expelling SDS from the cavity of β-CD due to the competitive inclusion complexation, which is consistent with our conjecture. Based on this, a schematic representation of LCA detection me- chanism is depicted in Fig. 9. SDS as the guest molecule was initially included into β-CD, which prevented it from being adsorbed at the LCs/ aqueous interface and cause LCs to adopt the tilted ordering (Fig. 9a). While in the presence of LCA solution, LCA would compete against SDS and finally gain entry into the cavity of β-CD. The excluded SDS dec- orates the fluid interface and induces LCs to undergo an ordering transition from tilted (Fig. 9a) to homeotropic (Fig. 9b) state, corre- sponding to the bright (Fig. 9c) to dark (Fig. 9d) shift in the optical images.
4. Conclusions
The LCs-based sensor for LCA detection was fabricated using a copper grid cell with SDS and β-CD miXture, originating from the competitive host-guest inclusion. The optimum concentration for SDS and β-CD to construct the sensor was 0.50 mM and 1.00 mM, respec- tively, which was ascertained by POM and surface tension techniques. The detection limit of LCA was around 2 μM whether in aqueous so- lution or in human urine. The possible detection mechanism of LCA was due to the dominant inclusion of LCA/β-CD, the expelled SDS from the cavity of β-CD was again adsorbed at the LCs/aqueous interface and subsequently caused the ordering transition of 5CB from tilted to homeotropic state. Correspondingly, the bright-to-black alteration in the optical appearance of LCs was observed under POM. This work provides a convenient, low-cost and label-free assay for the detection of LCA which shows potential and promising prospects in sensing appli- cations.
Acknowledgments
This work was supportedby Natural Science Foundation of China (No. 21373128), Scientific and Technological Projects of Shandong Province of China (No. 2014GSF117001).
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.colsurfb.2018.09.071.
References
[1] S.M. Vogel, M.R. Bauer, A.C. Joerger, R. Wilcken, T. Brandt, D.B. Veprintsev,
F.M. Boeckler, Lithocholic acid is an endogenous inhibitor of MDM4 and MDM2, Proc. Natl. Acad. Sci. U. S. A. 109 (2012) 16906–16910.
[2] S.E. Lucangioli, G. Castano, M.D. Contin, V.P. Tripodi, Lithocholic acid as a bio- marker of intrahepatic cholestasis of pregnancy during ursodeoXycholic acid treatment, Ann. Clin. Biochem. 46 (2009) 44–49.
[3] H. Schneider, H. Fiander, K.A. Harrison, M. Watson, G.W. Burton, P. Arya,
Inhibitory potency of lithocholic acid analogs and other bile acids on glucur- onosyltransferase activity in a colon cancer cell line, Bioorg. Med. Chem. Lett. 6 (1996) 637–642.
[4] Q. Du, Y. Zhang, Y. Pan, T. Duan, Lithocholic acid-induced placental tumor necrosis
factor-α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cho- lestasis of pregnancy, Hepatol. Res. 44 (2014) 532–541.
[5] B.W. Katona, S. Anant, D.F. Covey, W.F. Stenson, Characterization of enantiomeric bile acid-induced apoptosis in colon cancer cell lines, J. Biol. Chem. 284 (2009) 3354–3364.
[6] H. Ajouz, D. Mukherji, A. Shamseddine, Secondary bile acids: an underrecognized
cause of colon cancer, World J. Surg. Oncol. 12 (2014) 164-164.
[7] Y. Han, T. Haraguchi, S. Iwanaga, H. Tomotake, Y. Okazaki, S. Mineo, A. Moriyama,
J. Inoue, N. Kato, Consumption of some polyphenols reduces fecal deoXycholic acid and lithocholic acid, the secondary bile acids of risk factors of colon cancer, J. Agric. Food Chem. 57 (2009) 8587–8590.
[8] A.K. Deo, S.M. Bandiera, Biotransformation of lithocholic acid by rat hepatic mi-
crosomes: metabolite analysis by liquid chromatography/mass spectrometry, Drug Metab. Dispos. 36 (2008) 442–451.
[9] K. Bentayeb, R. Batlle, C. Sanchez, C. Nerin, C. Domeno, Determination of bile acids in human serum by on-line restricted access material-ultra high-performance liquid chromatography-mass spectrometry, J. Chromatogr. B 869 (2008) 1–8.
[10] Y. Yang, X. Yang, Y.L. Liu, Z.M. Liu, H.F. Yang, G.L. Shen, R.Q. Yu, Optical sensor
for lithocholic acid based on multilayered assemblies from polyelectrolyte and cy- clodextrin, J. Photochem. Photobiol. A: Chem. 171 (2005) 137–144.
[11] S. Li, W.C. Purdy, Cyclodextrins and their applications in analytical chemistry, Chem. Rev. 92 (1992) 1457–1470.
[12] A.J. Valente, O. Soderman, The formation of host-guest complexes between sur- factants and cyclodextrins, Adv. Colloid Interface Sci. 205 (2014) 156–176.
[13] D.A. Uhlenheuer, L.G. Milroy, P. Neirynck, L. Brunsveld, Strong supramolecular control over protein self-assembly using a polyamine decorated β-cyclodextrin as synthetic recognition element, J. Mater. Chem. 21 (2011) 18919.
[14] J.M. Brake, N.L. Abbott, An experimental system for imaging the reversible ad- sorption of amphiphiles at aqueous-liquid crystal interfaces, Langmuir 18 (2002) 6101–6109.
[15] J.M. Brake, A.D. Mezera, N.L. Abbott, Effect of surfactant structure on the or-
ientation of liquid crystals at aqueous-liquid crystal interfaces, Langmuir 19 (2003) 6436–6442.
[16] T. Bera, J. Deng, J. Fang, Protein-induced configuration transitions of polyelec- trolyte-modified liquid crystal droplets, J. Phys. Chem. B 118 (2014) 4970–4975.
[17] D. Hartono, C.Y. Xue, K.L. Yang, L.Y.L. Yung, Decorating liquid crystal surfaces with
proteins for real-time detection of specific protein-protein binding, Adv. Funct. Mater. 19 (2009) 3574–3579.
[18] L.N. Tan, V.J. Orler, N.L. Abbott, Ordering transitions triggered by specific binding of vesicles to protein-decorated interfaces of thermotropic liquid crystals, Langmuir 28 (2012) 6364–6376.
[19] Y. Zhao, N. Mahaja, J. Fang, Self-assembled cylindrical lipid tubules with a bi-
refringent core, Small 2 (2006) 364–367.
[20] A.D. Price, D.K. Schwartz, DNA hybridization-induced reorientation of liquid crystal anchoring at the nematic liquid crystal/aqueous interface, J. Am. Chem. Soc. 130 (2008) 8188–8194.
[21] S. Munir, S.Y. Park, Liquid crystal-based DNA biosensor for myricetin detection,
Sens. Actuators B 233 (2016) 559–565.
[22] H. Tan, X. Li, S. Liao, R. Yu, Z. Wu, Highly-sensitive liquid crystal biosensor based on DNA dendrimers-mediated optical reorientation, Biosens. Bioelectron. 62 (2014) 84–89.
[23] C.H. Jang, M.L. Tingey, N.L. Korpi, G.J. Wiepz, J.H. Schiller, P.J. Bertics,
N.L. Abbott, Using liquid crystals to report membrane proteins captured by affinity microcontact printing from cell lysates and membrane extracts, J. Am. Chem. Soc. 127 (2005) 8912–8913.
[24] M. Omer, M. Khan, Y.K. Kim, J.H. Lee, I.K. Kang, S.Y. Park, Biosensor utilizing a
liquid crystal/water interface functionalized with poly(4-cyanobiphenyl-4′-oXyun- decylacrylate-b-((2-dimethyl amino) ethyl methacrylate)), Colloids Surf. B 121 (2014) 400–408.
[25] V.K. Gupta, J.J. Skaife, T.B. Dubrovsky, N.L. Abbott, Optical amplification of li-
gand-receptor binding using liquid crystals, Science 279 (1998) 2077–2080.
[26] H.J. Kim, J. Rim, C.H. Jang, Liquid-crystal-based immunosensor for diagnosis of tuberculosis in clinical specimens, ACS Appl. Mater. Interfaces 9 (2017) 21209–21215.
[27] X. Ding, K.L. Yang, Antibody-free detection of human chorionic gonadotropin by
use of liquid crystals, Anal. Chem. 85 (2013) 10710–10716.
[28] P. Popov, L.W. Honaker, E.E. Kooijman, E.K. Mann, A.I. Jákli, A liquid crystal biosensor for specific detection of antigens, Sens. Bio-Sensing Res. 8 (2016) 31–35.
[29]
C.H. Chuang, Y.C. Lin, W.L. Chen, Y.H. Chen, Y.X. Chen, C.M. Chen, H.W. Shiu,
L.Y. Chang, C.H. Chen, C.H. Chen, Detecting trypsin at liquid crystal/aqueous in- terface by using surface-immobilized bovine serum albumin, Biosens. Bioelectron. 78 (2016) 213–220.
[30] Y. Wang, L. Zhou, Q. Kang, L. Yu, Simple and label-free liquid crystal-based sensor
for detecting trypsin coupled to the interaction between cationic surfactant and BSA, Talanta 183 (2018) 223–227.
[31] F. Zuo, Z. Liao, C. Zhao, Z. Qin, X. Li, C. Zhang, D. Liu, An air-supported liquid crystal system for real-time reporting of host-guest inclusion events, Chem. Commun. 50 (2014) 1857–1860.
[32] S. Munir, S.Y. Park, The development of a cholesterol biosensor using a liquid
crystal/aqueous interface in a SDS-included beta-cyclodextrin aqueous solution, Anal. Chim. Acta 893 (2015) 101–107.
[33] J. Deng, X. Lu, C. Constant, A. Dogariu, J. Fang, Design of beta-CD-surfactant complex-coated liquid crystal droplets for the detection of cholic acid via compe- titive host-guest recognition, Chem. Commun. 51 (2015) 8912–8915.
[34] G. Li, B. Gao, M. Yang, L.C. Chen, X.L. Xiong, Homeotropic orientation behavior of
nematic liquid crystals induced by copper ions, Colloids Surf. B 130 (2015) 287–291.
[35] Q.Z. Hu, C.H. Jang, Liquid crystal-based sensors for the detection of heavy metals using surface-immobilized urease, Colloids Surf. B 88 (2011) 622–626.
[36] Y. Wang, Q. Hu, T. Tian, Y. Gao, L. Yu, A liquid crystal-based sensor for the simple and sensitive detection of cellulase and cysteine, Colloids Surf. B 147 (2016) 100–105.
[37] A. Bremmelgaard, J. Sjövall, Bile acid profiles in urine of patients with liver dis-
eases, Eur. J. Clin. Invest. 9 (1979) 341–348.
[38] E. Alami, S. Abrahmsén-Alami, J. Eastoe, I. Grillo, R.K. Heenan, Interactions be- tween a nonionic gemini surfactant and cyclodextrins investigated by small-angle neutron scattering, J. Colloid Interface Sci. 255 (2002) 403–409.
[39] V.C. Reinsborough, V.C. Stephenson, Inclusion complexation involving sugar-con-
taining species: β-cyclodext, Can. J. Chem. 82 (2004) 45–49.
[40] V. Bernat, C. Ringardlefebvre, G.L. Bas, B. Perly, F. Djedaïnipilard, S. Lesieur, Inclusion complex of n-octyl beta-d-glucopyranoside and alpha-cyclodextrin in aqueous solutions: thermodynamic and structural characterization, Langmuir 24
(2008) 3140–3149.
[41] J.L. Staudinger, B. Goodwin, S.A. Jones, D. Hawkins-Brown, K.I. MacKenzie,
A. LaTour, Y. Liu, C.D. Klaassen, K.K. Brown, J. Reinhard, T.M. Willson, B.H. Koller,
S.A. Kliewer, The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toXicity, Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 3369–3374.
[42] Y. Cao, X.Y. Hu, Y. Li, X. Zou, S. Xiong, C. Lin, Y.Z. Shen, L. Wang, Multistimuli- responsive supramolecular vesicles based on water-soluble pillar[6]arene and SAINT complexation for controllable drug release, J. Am. Chem. Soc. 136 (2014) 10762–10769.
[43] R. Palepu, V.C. Reinsborough, Surfactant-cyclodextrin interactions by conductance
measurements, Can. J. Chem. 66 (1988) 325–328.
[44] Z. Yang, R. Breslow, Very strong binding of lithocholic acid Lithocholic acid to β-cyclodextrin, Tetrahedron Lett. 38 (1997) 6171–6172.