
==== Front
Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

70624
10.1038/s41598-024-70624-y
Article
An efficient chemiluminescent probe based on Ni-doped CsPbBr3 perovskite nanocrystals embedded in mesoporous SiO2 for sensitive assay of L–cysteine
Salari Rana
Amjadi Mohammad amjadi@tabrizu.ac.ir

https://ror.org/01papkj44 grid.412831.d 0000 0001 1172 3536 Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, 5166616471 Iran
6 9 2024
6 9 2024
2024
14 2087113 5 2024
19 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
This study presents an efficient chemiluminescence (CL) probe based on perovskite nanocrystals (NCs) for detection of L–cysteine (L–Cys). It consists of nickel–doped CsPbBr3 NCs embedded in the mesoporous SiO2 matrix as CL reagent and cerium (IV) as an oxidant in aqueous environment. The probe was designed for the highly selective determination of L–Cys based on its remarkable enhancing effect on the CL intensity. The colloidal nanocomposite of nickel–doped CsPbBr3 NCs@SiO2 with photoluminescence quantum yield of 58% was fabricated by ligand–assisted re–precipitation method and characterized by using UV–Vis absorption, FT–IR, X–ray diffraction, and transmission electron microscopy. The sensor was utilized to determine L–Cys in the linear concentration range of 20–300 nM with a detection limit of 12.8 nM. Direct chemical oxidation of Ni–doped CsPbBr3 NCs@SiO2 by Ce(IV) was the single cause of the formation of the excited-state NCs and subsequent production of CL. The developed probe provides outstanding selectivity towards L–Cys over structurally related compounds. Accurate determination of L–Cys in human serum samples was achieved without interference, and the results were confirmed by HPLC method.

Keywords

Doped perovskite
Quantum dots
Chemiluminescence
Amino acid
Subject terms

Analytical chemistry
Nanoscale materials
issue-copyright-statement© Springer Nature Limited 2024
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pmcIntroduction

Lead halide perovskites, as a relatively new group of colloidal semiconductor nanocrystals (NCs) with an extensive range of achievable structures exhibit outstanding optical properties1. Perovskite nanomaterials with diverse morphologies could be obtained through simple and cost–effective synthesis processes, by changing the surfactant ligands, ion ratio, reaction temperature, and time2. Colloidal NCs, have promising prospects as applicable materials for preparing probes with analyzing purposes due to high native quantum efficiencies, wide ranges of tunable absorption and emission, narrow spectral width, and reduced photoluminescence (PL) blinking3. Doping process in metal halide perovskites produces various beneficial attributes such as heightened stability, improved charge transport, prolonged carrier lifetime, intensified luminescence, and tunable band gap4–6. Diverse metal elements, including main metal cations, transition metal cations, and rare earth metal cations, have been doped in the perovskite halide crystal construction7. In general, existence of metal ions in the composition of Pb–based perovskites reduces the toxicities of these nanomaterials while bringing in some other channel of energy transfer in the host that can conduct unique optical and electrical properties in the perovskite structure8. For the current study, we selected nickel as a dopant for CsPbBr3 perovskite NCs due to various reasons. Firstly, Ni2+ has a strong affinity for octahedral coordination with halide ions. Secondly, the ionic radii of Pb2+ and Ni2+ are close, making the replacement of Ni2+ with Pb2+ and the shaping of coordination compounds easy. Thirdly, doping Ni2+ ions reduces the toxicity of Pb–based compounds. Finally, substitution of these ions leads to an increase in PLQY and photostability 9. It was discovered that Ni2+ doping can restrict the phase change of perovskite NCs and considerably improve their stability10. Nevertheless, the stability of perovskite nanomaterials solution in environmental conditions has consistently been a major subject that limits its empirical application. To overcome this problem, researchers in the field of nanomaterials have recently made preparations to enhance the stability of these nanostructures by inserting them into polymer coating11, molecularly imprinted polymers12, porous silica13, organometallic structures14, phospholipid coating15, etc.

In the present work, Ni–doped perovskite NCs were synthesized within mesoporous SiO2 structural holes as host–guest template without structure and optical properties change. The presence of SiO2 mesoporous layer as well as Ni2+ ions in the structure of perovskite NCs preserves the optical properties and increases the environmental stability of the nanocomposite for one month.

L–Cysteine (L–Cys) is a vital thiol–containing amino acid with antioxidant properties. It plays a crucial role in metabolic regulation, signal transduction, and gene expression. Important biological functions of L–Cys in the human body include protein synthesis, structure, detoxification and metal ion binding16, but heightened levels, have been linked to an increased risk of some diseases. Common disorders associated with cysteine include cystinosis, a genetic condition that leads to L–Cys accumulation in lysosomes, and cystinuria, which is characterized by high concentrations of L–Cys in the urine. Moreover, unusual quantity of L–Cys has been associated with several illnesses such as hematopoiesis cut down, loss of hair pigment, liver injuries, leisurely growth, loss of muscle, skin lesions, and cancer17. Therefore, the continuous monitoring of L–Cys concentration in urine, plasma, and pharmaceuticals in real time consistently commands significant attention. In recent years, several techniques based on different principles, have been published for this purpose, for instance, HPLC18, spectrofluorometry19, spectrophotometry20, and electrochemical approaches21. Despite the sensitivity and precision of these methods, they have significant drawbacks like photobleaching, scattered light, poor light penetration, and being laborious or uneconomical. Consequently, it is imperative to develop a sensitive and selective yet simple platform for detecting L–Cys. Chemiluminescence (CL) is a process where light is produced through a chemical reaction. This phenomenon can be classified into two types: direct and indirect CL, each showcasing different energy conversion mechanisms. In direct CL, a chemiluminescent substrate is first oxidized to generate a highly energetic and unstable intermediate, which then decomposes to produce an excited luminogenic species that emits photons during its decay to the ground state. Indirect CL typically involves an energy transfer process from an excited state intermediate to a nearby fluorophore. The majority of features of CL are akin to fluorescence, with the key difference being that while fluorescence relies on an external light source for excitation, CL generates its own excitation energy through chemical reactions22. CL is considered as one the simplest analytical methods for measuring different species with low detection limit, high sensitivity, and quite broad linear range23. But despite these advantages, its usage is not so widespread mainly because of limited number of efficient CL systems. Therefore, many researchers have focused on developing new CL systems with innovative materials. One of such materials are perovskite NCs. However, despite their unique optical features, their application in CL sensing is rare. This may be due to the poor stability of pristine perovskite in aqueous solutions. However, by improving the stability of these NCs in polar solvents through coating with inert materials like silica and organic polymers, researchers can effectively harness the high capacities of these NCs for designing CL probes with high sensitivity.

Our group has previously reported the first CL sensor based on perovskite NCs for sensitive measurement of the antibiotic Cefazolin24. In that work we had used CsPbBr3 NCs dispersed in a mixture of toluene and hexane for enhancing a weak CL reaction. The main aim of this work is investigating direct CL of more efficient and stable perovskite in aqueous environment. For this purpose, we prepared Ni–doped CsPbBr3 NCs embedded in mesoporous silica (Ni–doped CsPbBr3 NCs@SiO2) which exhibited a brilliant fluorescence and good stability. This nanocomposite produced an intense CL upon direct reaction with Ce (IV). Based on the specific interaction of nanocomposite with L–Cys, which leads to considerable enhancing of CL signal, a sensitive and selective method was developed for determination of this biomolecules in serum samples.

Experimental

Materials

N, N-dimethylformamide (DMF), nickel bromide (NiBr2), cesium bromide (CsBr), isopropyl alcohol (2-propanol), oleic acid (OA), hexadecyltrimethylammonium bromide (CTAB), sodium hydroxide (NaOH), barium hydroxide (Ba(OH)2), Zinc sulfate (ZnSO4), cerium sulfate (CeSO4.4H2O) and L-cysteine from Merck Co (Darmstadt, Germany). Oleylamine (OAm), lead bromide (PbBr2) and tetraethyl orthosilicate (TEOS) were purchased from Sigma-Aldrich (USA). Homocysteine was purchased from Axis-shield Diagnostic Ltd, (UK). Ethanol was provided by Mojallali Co (Iran). All chemicals used were of analytical reagent grade. The ultra-pure deionized water (DI) was applied throughout. Ce(IV) solution (0.01 M) was prepared in 0.2 M H2SO4. A stock 1.0 mM solution of L–Cys was prepared daily in DI water.

Instrumentation

Transmission electron microscopy (TEM) (Leo 906, Zeiss, Germany and Philips BioTwin, the Netherlands) was used for the identification of the structure and the size of nanomaterials. PL spectra were recorded by a Jasco FP-8300 spectrofluorimeter (Japan) with slit width of both monochromators set at 5 nm (λex = 370 nm). UV–Vis absorption spectra were collected on a cary-100 spectrophotometer (Varian, Australia). A Fourier transform infrared spectrophotometer (Bruker Co., Germany) was used to achieve (FT-IR) spectra. XRD pattern was gathered over the 2θ range of 10–70º using Tongda TD–3700 diffractometer (China, which used Cu Kα as radiation source). Energy dispersive X–ray spectroscopy (EDX, MIRA III, France) was used for determination of elemental composition of nanomaterials. The CL assay was accomplished using a LUMAT LB 9507 chemiluminometer, which is equipped with an auto-injector (Berthold, Germany). Smartline 1000 KNAUER (Germany) HPLC chromatography technique was used as a standard method for measuring L–cysteine and homocysteine.

Synthesis of colloidal Ni–doped CsPbBr3 NCs embedded in mesoporous SiO2

Colloidal solution of Ni–doped CsPbBr3 NCs@SiO2 was made through the supersaturation recrystallization process which was previously reported in the literature25 with slight modification. Firstly, 0.085 mg (0.4 mmol) of CsBr, 147 mg (0.4 mmol) of PbBr2, as well as 200 µL of OAm and 500 µL of OA were added into a container having 5.0 mL of DMF. To complete the dissolution of solids, the temperature of the solution was increased to about 70 ºC for about 20 min. 1.0 mL of the above milky white mixture and also different amounts of 10 mmol NiBr2 (2.18 g in 10 ml DMF) was rapidly added to a container having 0.01g SiO2 and 10.0 mL of isopropanol under vigorous stirring. The mixture was stirred for one min. The color of the obtained colloidal solution was intense orange. The as–prepared colloid was purified via centrifugation at 6000 rpm for 5 min. The residue was dispersed in isopropanol and stored at 4 ºC in the dark (stable for about one month). Different amounts of NiBr2 solutions were utilized: 0, 0.04, 0.08, 0.16, 0.24, and 0.32 ml, while the total amount of the PbBr2/CsBr mixed solution was kept at 1.0 ml. The amount of Ni2+ was modified by adjusting the molar ratio of NiBr2 and PbBr2 (from Ni: Pb = 0.5:1 to 4:1). The composition and preparation conditions for different NCs (undoped, Ni-doped, and Ni-doped@SiO2) are summarized in Table S1 (ESM).

Chemiluminescence assay of L–Cys

For analyzing L–Cys, 200 µL of Ni–doped CsPbBr3 NCs@SiO2 and various concentrations of standard solution of L–Cys were added into a 3-mL cell, and the volume was adjusted to 850 µL with DI water. Afterward, 150 µL 0.01 M Ce(IV) was auto–injected. In this way, the detection of L–Cys was performed by collecting the maximum response of CL as an analytical signal.

Biological sample preparation

Human serum samples were obtained from the Blood Transfusion Center (Tabriz, Iran). To precipitate serum proteins, 2.0 mL of Ba(OH)2 (0.1M) and 1.8 mL of ZnSO4 (0.1M) were injected into a test tube containing 0.5 mL of serum. The solution was centrifuged for 45 min at 6000 rpm and supernatant was passed through a top syringe filter. The obtained clear solution was diluted to 50 mL. Then 100 µL of this solution was added to the CL cell and measured according to the assay procedure. For recovery tests, a certain amount of L–Cys was added to the sample before pretreatment step.

Results and discussion

Characterization and synthesis of Ni–doped CsPbBr3 NCs@SiO2

Ni–doped CsPbBr3 NCs@SiO2 nanocomposite with high efficiency was prepared using a ligand reprecipitation route. The surfactant ligands as well as reaction temperature play crucial role in determining the shape, size, and surface properties of colloidal perovskite nanocrystals2. The acid–base organic ligands system was provided through oleic acid and oleylamine with long carbon chain.

Pristine CsPbBr3 NCs have poor colloidal stability and relatively low quantum yield. In addition to surface passivation, doping metal cations through cation exchange followed by anion exchange to the crystal lattice of perovskites can induce new optical properties and improve their stability4. According to Fig. 1a, the pristine CsPbBr3 NCs demonstrate green emission at the wavelength of 525 nm, with the PL quantum yield (PLQY) of approximately 25%. However, with the introduction of Ni2+ into the structure of the CsPbBr3, the Ni–doped CsPbBr3 NCs with sharp green emission at 535 nm along with greater QY (64%) is obtained. As indicated in the Fig. 1b and Table S2 (ESM), the QY of the PL gradually increases with the rise of Ni to Pb mole ratio. On the other hand, at higher nickel concentrations, the emission blue shifts from 535 to 516 nm probably due to the quantum confinement effect. The distinct size difference between Pb2+ (radius ~ 1.19 Å) and Ni2+ (radius ~ 0.69 Å) probably creates specific planar defects in the doped perovskites structure. Excitons are confined within domains between these defects. Since the size of domains between defects is reduced by increasing dopant concentration, a slight blue shift in the PL peak is observed 26. As illustrated in Fig. 1a, addition of Ni2+ to the perovskite structure significantly improves the optical properties of these NCs; when the Ni: Pb feeding ratio is increased to 2.0, the PLQY increases remarkably up to 64% (as measured by using fluorescein (QY = 92%) as a reference). Figure 1c exhibits the absorption spectra of undoped CsPbBr3 NCs and Ni–doped CsPbBr3 NCs@SiO2 with varying amounts of Ni2+ (with a molar ratio of Ni:Pb = 0.5:1, 1:1, 2:1, 3:1, and 4:1). By addition of Ni2+ ions to the crystal structure of perovskite, the band gap energy calculated according to Tauc plot, is almost constant for Ni:Pb ratios of up to 3:1 (around 2.36 eV). However, at Ni:Pb ratio of 4:1 an increase in band gap to 2.47 eV is observed.Fig. 1 (a) PL spectra of undoped and Ni–doped CsPbBr3 NCs and Ni–doped CsPbBr3 NCs embedded in SiO2. (b) PL spectra of Ni–doped CsPbBr3 NCs@SiO2 at various Ni: Pb mole ratio. (c) UV–Vis spectra of Ni–doped CsPbBr3 NCs@SiO2 at various Ni: Pb mole ratio.

Transmission electron microscopy (TEM) of Ni–doped CsPbBr3 NCs embedded in SiO2 mesoporous scaffolds is presented in Fig. 2. The average diameter of the nanoparticles was determined to be 36 ± 4 nm. Closer look at these particles shows small NCs formed in the pores of SiO2. The TEM images of pristine CsPbBr3 NCs as well as Ni–doped CsPbBr3 NCs prepared in order to compare their behavior, are given in Fig. S1 (ESM). Their average diameters are 17 ± 5 nm and 21 ± 5 nm, respectively. In situ growth of NCs in the SiO2 pores leads to size control and reduction of particle aggregation. According to TEM results (inset of Fig. 2), the sizes of Ni–doped CsPbBr3 NCs formed in the pores are much smaller than free NCs which is due to the small size of SiO2 pores. This is consistent with previous reports27 The crystal structures of CsPbBr3 NCs, Ni–doped CsPbBr3 NCs and Ni–doped CsPbBr3 NCs@SiO2 were determined using X–ray diffraction (XRD). According to the XRD patterns (Fig. 3), the main peaks of (100), (110), (200), (210), (211), and (220) were observed at a 2θ of about 15.4°, 21.8°, 30.8°, 34.5, 37.9°, and 43.9°, respectively. The results showed that all samples had the same crystal structure as the cubic phase CsPbBr3 (COD ID: 1,533,062), and there was no overall structural change after doping (Fig.S2). Based on these results, it seems that Ni2+ ions are efficiently replacing Pb2+ ions in the CsPbBr3 lattice9,28. The elemental composition, mapping (Fig. S3), and comparative FTIR spectra (Fig.S4) of CsPbBr3 NCs, Ni–doped CsPbBr3 NCs and Ni–CsPbBr3 NCs@SiO2 are reported in detail in ESM.Fig. 2 TEM image of Ni–doped CsPbBr3 NCs@SiO2 (inset is the magnified image of a single particle showing NCs in pores of SiO2).

Fig. 3 XRD patterns of undoped CsPbBr3 NCs, mesoporous SiO2, Ni–doped CsPbBr3 NCs, and Ni–doped CsPbBr3 NCs@SiO2.

We comparatively investigated the stability of synthesized NCs. As shown in Fig. S5a, in the case of undoped CsPbBr3 NCs, a non-luminescent orange precipitate formed after 5 days which the implies its instability and phase change. Unwrapped Ni–doped NCs stayed stable for about two weeks. As can be seen from Fig. S5b, after 16 days a large shift in PL wavelength and a decrease in its intensity observed. On the other hand, Ni–doped CsPbBr3 NCs@SiO2 demonstrated exceptional durability for almost one month in isopropyl alcohol, with a loss of less than 14% of initial PL intensity after 30 days (Fig. S5c). Finally, as shown in Fig.S6, the PL intensity of Ni–doped CsPbBr3 NCs@SiO2 dispersed in isopropyl alcohol remains almost unchanged after injection in water for 60 min. It is clear that the insertion into mesoporous SiO2 provides good stability for Ni–doped CsPbBr3 NCs in water.

Direct chemiluminescence of Ni–doped CsPbBr3 NCs@SiO2

Firstly, we examined the CL reaction of Ni–doped CsPbBr3 NCs@SiO2 with various concentrations of commonly used oxidants (including Ce(IV), KMnO4, H2O2, KIO4 and K3Fe(CN)6). According to the achieved results, all oxidants except KIO4, can directly elicit a CL from Ni–doped CsPbBr3 NCs@SiO2. As illustrated in Fig. 4, Ce(IV) produces the most intense CL signal, so Ce(IV) was picked as the oxidant for the CL reaction. The exact reason why Ce(IV) gives highest CL intensity is not known for us, but better matching of energy produced during the oxidation reaction with Ce(IV) to the excitation energy required to form the excited state of Ni–doped CsPbBr3 NCs@SiO2 may explain this phenomenon. It should be mentioned that high concentrations of KMnO4, leads to a remarkable decrease in the CL intensity which can be attributed to its self-absorption effect.Fig. 4 Effect of different concentrations of oxidants on the CL intensity of Ni–doped CsPbBr3 NCs@SiO2 (200 µL). All oxidants were in basic medium (NaOH, 0.1 M) except KMnO4 that was in acidic medium (H2SO4, 0.02 M), and Ce(IV) which prepared in sulfuric acid medium (0.2 M).

As shown in the CL kinetic profile (Fig. 5), the maximum intensity of direct CL of Ni–doped CsPbBr3 NCs@SiO2 induced by Ce(IV) is reached within 1 s after injection of the oxidant. The normalized kinetic profiles given in Fig. S7 (ESM) better show this point. For comparison, the CL profile of undoped and Ni–doped NCs in reaction with Ce(IV) is also given in Fig. 5 (each in their optimal conditions). As can be seen, the signal increases in order of undoped CsPbBr3 NCs <  < Ni–doped CsPbBr3 NCs ~ Ni–doped CsPbBr3 NCs@SiO2. This is consistent with PLQYs of NCs (25% for undoped CsPbBr3 NCs compared to 64% and 58% for Ni–doped CsPbBr3 NCs and Ni–doped CsPbBr3 NCs@SiO2, respectively). Slightly higher CL of nanocomposite compared to Ni–doped CsPbBr3 is probably due to its porous nature, which leads to a more effective reaction. All kinetic profiles were obtained by automatic monitoring of CL signal over time after the injection of oxidant. This was carried out automatically by the luminometer instrument. It is important to note that each NC was studied under its optimal conditions. The faster signal decay rate in both nickel-doped NC samples may be attributed to their higher catalytic effect compared to undoped one.Fig. 5 CL kinetic profiles for Ce(IV) (3.5 mM)–CsPbBr3 NCs (250 µL), Ce(IV) (2 mM)–Ni–doped CsPbBr3 NCs (200 µL) and Ce(IV) (1.5 mM)–Ni–doped CsPbBr3 NCs@SiO2 (200 µL).

The role of primary ingredients of the synthesis process of nanocomposite (DMF, OAm, OA and 2–propanol) on the CL signal was investigated. As shown in Table S3, the precursor mixture did not have a significant influence on the CL. Therefore, the CL response is solely due to the Ni–doped CsPbBr3 NCs@SiO2. Based on the kinetic profiles, the direct oxidation of Ni–doped CsPbBr3 NCs@SiO2 by Ce(IV) occurred very quickly, so CL signal peaked within 1 s after the oxidant was injected into the solution. The response then began to decline and eventually disappeared after approximately 15 s. In contrast, the CL signal of undoped CsPbBr3 NCs with Ce(IV) reached its maximum within 2 s and diminished after about 5 s.

Possible reaction mechanism for CL

In order to determine the CL emitter as well as inspect the reaction mechanism, the CL spectrum of Ni–doped CsPbBr3 NCs@SiO2–Ce (IV) was obtained using a spectrofluorometer. For this purpose, the excitation source was turned off during the recording. According to Fig. 6 a CL peak emerges at around 545 nm which was comparable with the PL spectrum of Ni–doped CsPbBr3 NCs@SiO2. This indicates that the CL originates from the excited–state Ni–doped CsPbBr3 NCs@SiO2.Fig. 6 CL spectrum of reaction (a) in the absence and (b) in the presence of Ni–doped CsPbBr3 NCs@ SiO2. Inset (c) is the PL spectrum of Ni–doped CsPbBr3 NCs@SiO2.

To verify the reaction between Ni–doped CsPbBr3 NCs@SiO2 nanocomposite and Ce(IV), the PL spectrum of nanocomposite was recorded after mixing with this oxidant. As can be seen from Fig. S8 (ESM), the fluorescence peak of Ni–doped CsPbBr3 NCs@SiO2 at 535 nm decreases distinctly upon addition of Ce(IV) to the solution. We concluded that the reaction mechanism was a direct oxidation process. During the process, both electron and hole was created due to the chemical reaction. Some electrons could be thermally excited to the conduction band of Ni–doped CsPbBr3 NCs@SiO2, while Ce(IV) as a strong oxidant, could inject holes into its valence band. Due to the recombination of the electron–hole, energy is released and light emission occurs. A schematic diagram illustrating electron–hole recombination is depicted in Fig. S9 (ESM).

By removing dissolved oxygen from the solution using nitrogen bubbling, the CL signal decreased by a small amount (less than 5%), which shows that dissolved oxygen does not have significant effect on the CL emission.

Analytical application of CL system to L–Cys assay

When L–Cys is added to the system, there is a noticeable increase in the intensity of the CL signal. The high affinity of thiol group in L-Cys to perovskite NCs leads to a significant suppression of surface defects in the Ni–doped CsPbBr3 NCs@SiO2 nanocomposite structure29,30. According to Fig. S10, the PL intensity of Ni–doped CsPbBr3 NCs@SiO2 nanocomposite intensified with the addition of L–Cys, confirming this assumption. Thiol groups may be coordinated to the surface of the NCs at the Pb–rich defect sites31. The presence of Pb–S bond is confirmed through a distinct peak at around 804 cm-1 in the FTIR spectrum of perovskite NC in the presence of L-cysteine (Fig. S11)31. Anyway, the strong interaction of L-Cys with perovskite NCs can lead to surface passivation, reduction of non-radiative recombination centers, or alteration of energy transfer processes within NCs, all of which can contribute to the increase in CL intensity.

In order to attain the highest sensitivity in the determination of the L–Cys, the optimum quantity of SiO2 in the synthesis process was investigated with various molar ratios of Ni to Pb. According to experimental results (Table S4), with 0.01 g of SiO2 and Ni to Pb ratio of 2:1, the probe has the highest sensitivity toward L–Cys. Other experimental parameters were also optimized. According to the results (Fig. S12–S13), 1.5 mM of Ce(IV) and 200 µl of Ni–doped CsPbBr3 NCs@SiO2 were picked as optimum values.

As exhibited pictorially in Fig. 7 under optimal experimental conditions, by increasing the amount of L–Cys from 20 to 300 nM the CL intensity of Ce (IV)–Ni–doped CsPbBr3 NCs@SiO2 was linearly intensified. The related linear equation was I/I0 = 0.0037CL-Cys + 0.961 with R2 = 0.9991, where I/I0 is defined as the CL signal in the absence (I0) and in the presence (I) of L–Cys. In this way, the detection limit of the probe was calculated to be 12.8 nM based on 3sy/x/b (where sy/x is standard error of the regression, and b is the slope of the calibration curve)32. In order to study the repeatability of the established probe, the intra–day and inter–day precision as relative standard deviation (RSD) for seven replicate determinations of 75 nM L–Cys were calculated, which were 2.0% and 3.1% respectively. We also investigated the enhancing impact of L–Cys on the direct CL system of pristine CsPbBr3 QDs and Ni–CsPbBr3 NCs with Ce(IV) as oxidant. Table S5 (ESM) indicates that the use of these NCs creates calibration plots with more restricted linear ranges and higher detection limits and poor sensitivities than Ni–doped CsPbBr3 NCs@SiO2. It is interesting that the performance of nanocomposite is not only better than pristine perovskite but also than Ni–doped perovskite. This is probably due to the porous nature of SiO2 which leads to the accumulation of L–Cys molecules and their more effective interaction with Ni–doped CsPbBr3 NCs. Moreover, the poor repeatability of the signals obtained from Ni–doped CsPbBr3 NCs, indicates that its stability in water is low and cannot be relied upon. Anyway, the results suggest that Ni–CsPbBr3 NCs@SiO2 not only have a superior enhancing effect on the CL reaction but also have a higher affinity to L–Cys. These results specify that the performance of encapsulated perovskite NCs has been expressively improved compared with that of bare perovskite NCs. Table 1 compares the performance of our developed method for L–Cys with that of other CL methods. Our assay has equal or higher analytical performance compared to most reported CL–based methods.Fig. 7 Time profiles of Ce(IV)–Ni–doped CsPbBr3 NCs@SiO2 CL system with various concentrations of L–Cys and the related calibration plot (inset).

Table 1 Comparing the proposed method with some previously reported CL methods for the determination of L–Cys.

CL system	Linear range (µM)	Detection limit (nM)	References	
Ag NPs–luminol–H2O2	0.28–8	82.5	34	
Carbon dots–lucigenin	10–100	88 × 102	35	
Ag NPs–Ce(IV)–SO32-	0.005–1	2.5	36	
Au NPs–luminol–H2O2	0.001–7	0.29	37	
Ru(phen)32+–Ce(IV)	0.8– 40 and 40–1000	700	38	
Co–MOF–luminol	0.1–10	18	39	
C–dots–Ni(IV)	0.075–0.625	68 × 103	40	
Ni–CsPbBr3 NCs@ SiO2	0.02–0.3	12.8	Present work	

Selectivity of the designed CL probe was evaluated against some similar biological molecules and common inorganic ions that may found in serum samples. The achieved results are outlined in Table 2. As can be seen, the interference effect of most species in L–Cys determination was negligible. Homocysteine, a homolog of the cysteine with additional methylene bridge (–CH2), have no significant influence on the determination of L–Cys. It should be mentioned that, the concentration of L–Cys in human serum is naturally 240–360 µM, while that of homocysteine is normally below 12–15 μM33. So our method has an excellent selectivity for L–Cys, which may be attributed to the particular interaction of L–Cys with Ni–doped CsPbBr3 NCs@SiO2 which was discussed before.Table 2 Interferences of several common ions and biological species in determining L–Cys (150 nM).

Interfering species	Tolerance limit	
Na+, Cl-, Alanine, Glycine	10,000	
K+, Glucose, Sucrose	6000	
NO3-, Ca2+	3000	
Mg2+, Zn2+,Ba2+,SO42-, F-	2000	
Fe3+, Lactose	1500	
Fe2+, PO43-	1000	
I-, Cu2+	600	
Ascorbic acid, Uric acid, Tryptophan	200	
Glutathione	65	
Homocysteine	18	

It should be mentioned that current probe is quite stable in polar environments and produces reproducible results. However, since it is used in the liquid phase reactions, each test sample requires a separate probe.

Analysis of real sample

Ni–doped CsPbBr3 NCs@SiO2–Ce(IV) CL probe was exploited to determine L–Cys in various serum samples and the results are reported in Table 3. First, the L–Cys present in the samples was measured, then to confirm the accuracy of the method, the serum samples were spiked with specific concentration of L–Cys. The recoveries as well as Student t-tests are demonstrated the appropriate correlation of the achieved values. According to the satisfying recoveries from 92.5 to 108.0% with RSD of 1.3 to 7.2%, the fitness of the established CL probe for selective and sensitive assay of L–Cys in actual samples was approved. The accuracy of proposed method was further confirmed via HPLC method. The results are given in Table 3 and corresponding chromatograms are shown in Fig. S14.Table 3 Determination of L–Cys in serum samples.

Sample	Added (µM)	Found a Mean a ± RSD (%)	Recovery (%)	t-statistic b	Found c (HPLC method)	t-statistic d	
Serum I	0.0	147 ± 2.5	–	–	138.5 ± 3.6	2.3	
50	201 ± 1.3	102.0	2.6	
100	231 ± 4.1	93.5	2.9	
150	283 ± 7.0	95.0	3.52	
Serum II	0.0	238 ± 1.7	–	–	256.5 ± 4.1	2.9	
50	268 ± 7.2	92.5	2.0	
100	367 ± 3.5	108.0	3.7	
150	405 ± 2.8	104.0	2.3	
aMean of three determinations.

bt-Critical = 4.3 for n = 2, P = 0.05.

cMean of two determinations.

dt-Critical = 3.18 for n = 3, P = 0.05.

Conclusion

In this work, a CL probe with high sensitivity and remarkable stability has been introduced for selective detection of L–cysteine. The probe includes Ce(IV) as a strong oxidant and Ni–doped perovskite NCs wrapped by SiO2 as a CL reagent. The combination of Ni doping and SiO2 wrapping results in high PLQY and excellent structural stability of CsPbBr3 NCs, as well as high sensitivity to L–Cys. According to our results, the excited state Ni–doped CsPbBr3 NCs@SiO2 acts as an emitting species in CL reaction. The designed CL probe was used for the highly sensitive detection of L–Cys in human serum samples. The obtained results were confirmed by HPLC as a standard method.

Supplementary Information

Supplementary Information.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-024-70624-y.

Author contributions

R.S. performed the experiments, obtained data and wrote the draft of manuscript. M.A. supervised the work, provide the resources and wrote the final version of manuscript.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Weidman MC Goodman AJ Tisdale WA Colloidal halide perovskite nanoplatelets: An exciting new class of semiconductor nanomaterials Chem. Mater. 2017 29 5019 5030 10.1021/acs.chemmater.7b01384
Weidman, M. C., Goodman, A. J. & Tisdale, W. A. Colloidal halide perovskite nanoplatelets: An exciting new class of semiconductor nanomaterials. Chem. Mater. 29, 5019–5030 (2017).10.1021/acs.chemmater.7b01384
2. Pan A He B Fan X Liu Z Urban J Insight into the ligand-mediated synthesis of colloidal CsPbBr3 perovskite nanocrystals: The role of organic acid, base, and cesium precursors ACS Nano 2016 10 7943 7954 10.1021/acsnano.6b03863 27479080
Pan, A., He, B., Fan, X., Liu, Z. & Urban, J. Insight into the ligand-mediated synthesis of colloidal CsPbBr3 perovskite nanocrystals: The role of organic acid, base, and cesium precursors. ACS Nano 10, 7943–7954 (2016).27479080 10.1021/acsnano.6b03863
3. Bekenstein Y Koscher BA Eaton SW Yang P Alivisatos AP Highly luminescent colloidal nanoplates of perovskite cesium lead halide and their oriented assemblies J. Am. Chem. Soc. 2015 137 16008 16011 10.1021/jacs.5b11199 26669631
Bekenstein, Y., Koscher, B. A., Eaton, S. W., Yang, P. & Alivisatos, A. P. Highly luminescent colloidal nanoplates of perovskite cesium lead halide and their oriented assemblies. J. Am. Chem. Soc. 137, 16008–16011 (2015).26669631 10.1021/jacs.5b11199
4. Otero-Martínez C Ye J Sung J Pastoriza-Santos I Pérez-Juste J Colloidal metal-halide perovskite nanoplatelets: Thickness-controlled synthesis, properties, and application in light-emitting diodes Adv. Mater. 2022 34 2107105 10.1002/adma.202107105
Otero-Martínez, C., Ye, J., Sung, J., Pastoriza-Santos, I. & Pérez-Juste, J. Colloidal metal-halide perovskite nanoplatelets: Thickness-controlled synthesis, properties, and application in light-emitting diodes. Adv. Mater. 34, 2107105 (2022).10.1002/adma.202107105
5. Zhou Y Chen J Bakr OM Sun H-T Metal-doped lead halide perovskites: Synthesis, properties, and optoelectronic applications Chem. Mater. 2018 30 6589 6613 10.1021/acs.chemmater.8b02989
Zhou, Y., Chen, J., Bakr, O. M. & Sun, H.-T. Metal-doped lead halide perovskites: Synthesis, properties, and optoelectronic applications. Chem. Mater. 30, 6589–6613 (2018).10.1021/acs.chemmater.8b02989
6. Lu C-H Biesold-McGee GV Liu Y Kang Z Lin Z Doping and ion substitution in colloidal metal halide perovskite nanocrystals Chem. Soc. Rev. 2020 49 4953 5007 10.1039/C9CS00790C 32538382
Lu, C.-H., Biesold-McGee, G. V., Liu, Y., Kang, Z. & Lin, Z. Doping and ion substitution in colloidal metal halide perovskite nanocrystals. Chem. Soc. Rev. 49, 4953–5007 (2020).32538382 10.1039/C9CS00790C
7. Xu L Yuan S Zeng H Song J A comprehensive review of doping in perovskite nanocrystals/quantum dots: Evolution of structure, electronics, optics, and light-emitting diodes Mater. Today Nano 2019 6 100036 10.1016/j.mtnano.2019.100036
Xu, L., Yuan, S., Zeng, H. & Song, J. A comprehensive review of doping in perovskite nanocrystals/quantum dots: Evolution of structure, electronics, optics, and light-emitting diodes. Mater. Today Nano 6, 100036 (2019).10.1016/j.mtnano.2019.100036
8. Zhang X Li L Sun Z Luo J Rational chemical doping of metal halide perovskites Chem. Soc. Rev. 2019 48 517 539 10.1039/C8CS00563J 30556818
Zhang, X., Li, L., Sun, Z. & Luo, J. Rational chemical doping of metal halide perovskites. Chem. Soc. Rev. 48, 517–539 (2019).30556818 10.1039/C8CS00563J
9. Thawarkar S Rana PJS Narayan R Singh SP Ni-doped CsPbBr3 perovskite: Synthesis of highly stable nanocubes Langmuir 2019 35 17150 17155 10.1021/acs.langmuir.9b02450 31746613
Thawarkar, S., Rana, P. J. S., Narayan, R. & Singh, S. P. Ni-doped CsPbBr3 perovskite: Synthesis of highly stable nanocubes. Langmuir 35, 17150–17155 (2019).31746613 10.1021/acs.langmuir.9b02450
10. Yong Z-J Guo S-Q Ma J-P Zhang JY Li JY Doping-enhanced short-range order of perovskite nanocrystals for near-Unity violet luminescence quantum yield J. Am. Chem. Soc. 2018 140 9942 9951 10.1021/jacs.8b04763 30008218
Yong, Z.-J., Guo, S.-Q., Ma, J.-P., Zhang, J. Y. & Li, J. Y. Doping-enhanced short-range order of perovskite nanocrystals for near-Unity violet luminescence quantum yield. J. Am. Chem. Soc. 140, 9942–9951 (2018).30008218 10.1021/jacs.8b04763
11. Ghinaiya NV Park TJ Kailasa SK Synthesis of bright blue fluorescence and water-dispersible cesium lead halide perovskite quantum dots for the selective detection of pendimethalin pesticide J. Photochem. Photobiol. Chem. 2023 444 114980 10.1016/j.jphotochem.2023.114980
Ghinaiya, N. V., Park, T. J. & Kailasa, S. K. Synthesis of bright blue fluorescence and water-dispersible cesium lead halide perovskite quantum dots for the selective detection of pendimethalin pesticide. J. Photochem. Photobiol. Chem. 444, 114980 (2023).10.1016/j.jphotochem.2023.114980
12. Chi H Wang L Wang S Liu G An electrochemiluminescence sensor based on CsPbBr3 -zquantum dots and poly (3-thiophene acetic acid) cross-linked nanogold imprinted layer for the determination of benzo(a)pyrene in edible oils Food Chem. 2023 426 136508 10.1016/j.foodchem.2023.136508 37348399
Chi, H., Wang, L., Wang, S. & Liu, G. An electrochemiluminescence sensor based on CsPbBr3 -zquantum dots and poly (3-thiophene acetic acid) cross-linked nanogold imprinted layer for the determination of benzo(a)pyrene in edible oils. Food Chem. 426, 136508 (2023).37348399 10.1016/j.foodchem.2023.136508
13. Deng P Wang W Liu X Wang L Yan Y A hydrophobic polymer stabilized CsPbBr3 sensor for environmental pollutant detection New J. Chem. 2021 45 930 938 10.1039/D0NJ04498A
Deng, P., Wang, W., Liu, X., Wang, L. & Yan, Y. A hydrophobic polymer stabilized CsPbBr3 sensor for environmental pollutant detection. New J. Chem. 45, 930–938 (2021).10.1039/D0NJ04498A
14. Wang Q Xiong C Li J Deng Q Zhang X Wang S Chen M-M High-performance electrochemiluminescence sensors based on ultra-stable perovskite quantum dots@ZIF-8 composites for aflatoxin B1 monitoring in corn samples Food Chem. 2023 410 135325 10.1016/j.foodchem.2022.135325 36610091
Wang, Q. et al. High-performance electrochemiluminescence sensors based on ultra-stable perovskite quantum dots@ZIF-8 composites for aflatoxin B1 monitoring in corn samples. Food Chem. 410, 135325 (2023).36610091 10.1016/j.foodchem.2022.135325
15. Song W Wang D Tian J Qi G Wu M Encapsulation of dual-passivated perovskite quantum dots for bio-imaging Small 2022 18 2204763 10.1002/smll.202204763
Song, W., Wang, D., Tian, J., Qi, G. & Wu, M. Encapsulation of dual-passivated perovskite quantum dots for bio-imaging. Small 18, 2204763 (2022).10.1002/smll.202204763
16. Lačná J Foret F Kubáň P Capillary electrophoresis in the analysis of biologically important thiols Electrophoresis 2017 38 203 222 10.1002/elps.201600354 27611491
Lačná, J., Foret, F. & Kubáň, P. Capillary electrophoresis in the analysis of biologically important thiols. Electrophoresis 38, 203–222 (2017).27611491 10.1002/elps.201600354
17. Clemente Plaza N Reig García-Galbis M Martínez-Espinosa R Effects of the usage of l-Cysteine (l-Cys) on human health Molecules 2018 23 575 10.3390/molecules23030575 29510494
Clemente Plaza, N., Reig García-Galbis, M. & Martínez-Espinosa, R. Effects of the usage of l-Cysteine (l-Cys) on human health. Molecules 23, 575 (2018).29510494 10.3390/molecules23030575
18. Głowacki R Stachniuk J Borowczyk K A simple HPLC—UV method for simultaneous determination of cysteine and cysteinylglycine in biological fluids Acta Chromatogr. 2016 28 333 346 10.1556/1326.2016.28.3.4
Głowacki, R., Stachniuk, J. & Borowczyk, K. A simple HPLC—UV method for simultaneous determination of cysteine and cysteinylglycine in biological fluids. Acta Chromatogr. 28, 333–346 (2016).10.1556/1326.2016.28.3.4
19. Yan F Sun X Zu F Bai Z Jiang Y Fan K Wang J Fluorescent probes for detecting cysteine Methods Appl. Fluoresc. 2018 6 042001 10.1088/2050-6120/aad580 30039804
Yan, F. et al. Fluorescent probes for detecting cysteine. Methods Appl. Fluoresc. 6, 042001 (2018).30039804 10.1088/2050-6120/aad580
20. Abolghasemi-Fakhri Z Amjadi M Gold nanostar@graphene quantum dot as a new colorimetric sensing platform for detection of cysteine Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 2021 261 120010 10.1016/j.saa.2021.120010 34091360
Abolghasemi-Fakhri, Z. & Amjadi, M. Gold nanostar@graphene quantum dot as a new colorimetric sensing platform for detection of cysteine. Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 261, 120010 (2021).34091360 10.1016/j.saa.2021.120010
21. Liu Z Zhang H Hou S Ma H Highly sensitive and selective electrochemical detection of L-cysteine using nanoporous gold Microchim. Acta 2012 177 427 433 10.1007/s00604-012-0801-x
Liu, Z., Zhang, H., Hou, S. & Ma, H. Highly sensitive and selective electrochemical detection of L-cysteine using nanoporous gold. Microchim. Acta 177, 427–433 (2012).10.1007/s00604-012-0801-x
22. Yang M Huang J Fan J Du J Pu K Peng X Chemiluminescence for bioimaging and therapeutics: Recent advances and challenges Chem. Soc. Rev. 2020 49 6800 6815 10.1039/D0CS00348D 32929428
Yang, M. et al. Chemiluminescence for bioimaging and therapeutics: Recent advances and challenges. Chem. Soc. Rev. 49, 6800–6815 (2020).32929428 10.1039/D0CS00348D
23. Blau R Shelef O Shabat D Satchi-Fainaro R Chemiluminescent probes in cancer biology Nat. Rev. Bioeng. 2023 1 648 664 10.1038/s44222-023-00074-0
Blau, R., Shelef, O., Shabat, D. & Satchi-Fainaro, R. Chemiluminescent probes in cancer biology. Nat. Rev. Bioeng. 1, 648–664 (2023).10.1038/s44222-023-00074-0
24. Salari R Amjadi M Hallaj T Perovskite quantum dots as a chemiluminescence platform for highly sensitive assay of cefazolin Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 2023 285 121845 10.1016/j.saa.2022.121845 36152503
Salari, R., Amjadi, M. & Hallaj, T. Perovskite quantum dots as a chemiluminescence platform for highly sensitive assay of cefazolin. Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 285, 121845 (2023).36152503 10.1016/j.saa.2022.121845
25. Pan G Bai X Xu W Chen X Zhai Y Zhu J Shao H Ding N Xu L Dong B Mao Y Song H Bright bluelight emission of Ni2+ ion-doped CsPbClxBr3–x perovskite quantum dots enabling efficient light-emitting devices ACS Appl. Mater. Interfaces 2020 12 14195 14202 10.1021/acsami.0c01074 32093480
Pan, G. et al. Bright bluelight emission of Ni2+ ion-doped CsPbClxBr3–x perovskite quantum dots enabling efficient light-emitting devices. ACS Appl. Mater. Interfaces 12, 14195–14202 (2020).32093480 10.1021/acsami.0c01074
26. Paul S Bladt E Richter A Döblinger M Tong Y Huang H Dey A Bals S Debnath T Polavarapu L Feldmann J Manganese-doping-induced quantum confinement within host perovskite nanocrystals through ruddlesden–popper defects Angew. Chem. Int. Ed. 2020 59 6794 6799 10.1002/anie.201914473
Paul, S. et al. Manganese-doping-induced quantum confinement within host perovskite nanocrystals through ruddlesden–popper defects. Angew. Chem. Int. Ed. 59, 6794–6799 (2020).10.1002/anie.201914473
27. Shen J Wang Y Zhu Y Gong Y Li C A polymer-coated template-confinement CsPbBr3 perovskite quantum dot composite Nanoscale 2021 13 6586 6591 10.1039/D1NR00201E 33885538
Shen, J., Wang, Y., Zhu, Y., Gong, Y. & Li, C. A polymer-coated template-confinement CsPbBr3 perovskite quantum dot composite. Nanoscale 13, 6586–6591 (2021).33885538 10.1039/D1NR00201E
28. Kim H Bae S-R Lee T Lee H Kang H Enhanced optical properties and stability of CsPbBr3 nanocrystals through nickel doping Adv. Funct. Mater. 2021 31 2102770 10.1002/adfm.202102770
Kim, H., Bae, S.-R., Lee, T., Lee, H. & Kang, H. Enhanced optical properties and stability of CsPbBr3 nanocrystals through nickel doping. Adv. Funct. Mater. 31, 2102770 (2021).10.1002/adfm.202102770
29. Song H Yang J Lim S Lee J Jeong W Choi H Lee J Kim H Lee B Choi H On the surface passivating principle of functional thiol towards efficient and stable perovskite nanocrystal solar cells Chem. Eng. J. 2023 454 140224 10.1016/j.cej.2022.140224
Song, H. et al. On the surface passivating principle of functional thiol towards efficient and stable perovskite nanocrystal solar cells. Chem. Eng. J. 454, 140224 (2023).10.1016/j.cej.2022.140224
30. Chen S Wei J Pang Q Enhancing photoluminescence and stability of CsPbI3 perovskite quantum dots via cysteine post-processing Crystals 2022 13 45 10.3390/cryst13010045
Chen, S., Wei, J. & Pang, Q. Enhancing photoluminescence and stability of CsPbI3 perovskite quantum dots via cysteine post-processing. Crystals 13, 45 (2022).10.3390/cryst13010045
31. Wu W-B Wong Y-C Tan Z-K Wu J Photo-induced thiol coupling and C–H activation using nanocrystalline lead-halide perovskite catalysts Catal. Sci. Technol. 2018 8 4257 4263 10.1039/C8CY01240G
Wu, W.-B., Wong, Y.-C., Tan, Z.-K. & Wu, J. Photo-induced thiol coupling and C–H activation using nanocrystalline lead-halide perovskite catalysts. Catal. Sci. Technol. 8, 4257–4263 (2018).10.1039/C8CY01240G
32. Miller JN Miller JC Statistics and chemometrics for analytical chemistry 2010 Harlow Prentice Hall/Pearson
Miller, J. N. & Miller, J. C. Statistics and chemometrics for analytical chemistry (Prentice Hall/Pearson, Harlow, 2010).
33. Wang N Chen M Gao J Ji X He J Zhang J Zhao W A series of BODIPY-based probes for the detection of cysteine and homocysteine in living cells Talanta 2019 195 281 289 10.1016/j.talanta.2018.11.066 30625544
Wang, N. et al. A series of BODIPY-based probes for the detection of cysteine and homocysteine in living cells. Talanta 195, 281–289 (2019).30625544 10.1016/j.talanta.2018.11.066
34. Samadi-Maybodi A Akhoondi R Trace analysis of N -acetyl-L-cysteine using luminol–H2O2 chemiluminescence system catalyzed by silver nanoparticles Luminescence 2015 30 775 779 10.1002/bio.2819 25428294
Samadi-Maybodi, A. & Akhoondi, R. Trace analysis of N -acetyl-L-cysteine using luminol–H2O2 chemiluminescence system catalyzed by silver nanoparticles. Luminescence 30, 775–779 (2015).25428294 10.1002/bio.2819
35. Wang C Lan Y Yuan F Fereja T Lou B Han S Li J Xu J Chemiluminescent determination of L-cysteine with the lucigenin-carbon dot system Microchim. Acta 2020 187 50 10.1007/s00604-019-3965-9
Wang, C. et al. Chemiluminescent determination of L-cysteine with the lucigenin-carbon dot system. Microchim. Acta 187, 50 (2020).10.1007/s00604-019-3965-9
36. Yu X Wang Q Liu X Luo X A sensitive chemiluminescence method for the determination of cysteine based on silver nanoclusters Microchim. Acta 2012 179 323 328 10.1007/s00604-012-0893-3
Yu, X., Wang, Q., Liu, X. & Luo, X. A sensitive chemiluminescence method for the determination of cysteine based on silver nanoclusters. Microchim. Acta 179, 323–328 (2012).10.1007/s00604-012-0893-3
37. Yang P Chen Y Zhu Q Wang F Wang L Li Y Sensitive chemiluminescence method for the determination of glutathione, l-cysteine and 6-mercaptopurine Microchim. Acta 2008 163 263 269 10.1007/s00604-008-0006-5
Yang, P. et al. Sensitive chemiluminescence method for the determination of glutathione, l-cysteine and 6-mercaptopurine. Microchim. Acta 163, 263–269 (2008).10.1007/s00604-008-0006-5
38. Rezaei B Mokhtari A A simple and rapid flow injection chemiluminescence determination of cysteine with Ru(phen)32+–Ce(IV) system Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 2007 66 359 363 10.1016/j.saa.2006.03.005 16843051
Rezaei, B. & Mokhtari, A. A simple and rapid flow injection chemiluminescence determination of cysteine with Ru(phen)3 2+–Ce(IV) system. Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 66, 359–363 (2007).16843051 10.1016/j.saa.2006.03.005
39. Yang N Song H Wan X Fan X Su Y Lv Y A metal (Co)–organic framework-based chemiluminescence system for selective detection of l -cysteine The Analyst 2015 140 2656 2663 10.1039/C5AN00022J 25697303
Yang, N. et al. A metal (Co)–organic framework-based chemiluminescence system for selective detection of l -cysteine. The Analyst 140, 2656–2663 (2015).25697303 10.1039/C5AN00022J
40. Dong Y Su M Chen P Sun H Chemiluminescence of carbon dots induced by diperiodato-nicklate (IV) in alkaline solution and its application to a quenchometric flow-injection assays of paracetamol, L-cysteine and glutathione Microchim. Acta 2015 182 1071 1077 10.1007/s00604-014-1427-y
Dong, Y., Su, M., Chen, P. & Sun, H. Chemiluminescence of carbon dots induced by diperiodato-nicklate (IV) in alkaline solution and its application to a quenchometric flow-injection assays of paracetamol, L-cysteine and glutathione. Microchim. Acta 182, 1071–1077 (2015).10.1007/s00604-014-1427-y
