Recent Advances in Quantum Dots-Based Biosensors

*Meysam Safari*

#### **Abstract**

Biosensors can be developed using quantum dots (QDs). An inorganic nucleus with organic molecules attached to its surface is referred to as a QD, and they are a type of new fluorescent nanomaterial. QDs possess unique excellent optical properties and chemical properties, including broad excitation spectra, adjustable particle sizes, confined emission spectra, emission of multiple fluorescence colors, superior signal brightness, and extended fluorescence lifetime. QDs have abundant functional groups, which make it easy to form hybrid nanomaterials that perform analytically well. With functionalized sensing systems, we can detect metal ions, biomarkers, and antibiotics sensitively and selectively through the hybridization of QDs with nanomaterials. In this chapter, we first introduce the research trends in the application of QDs and then discuss their surface modification for biological applications.

**Keywords:** biosensors, quantum dots, biological applications, fluorescent nanomaterial

### **1. Introduction**

Semiconductor nanocrystals or quantum dots (QDs) are a type of novel fluorescent nanomaterial consisting of inorganic nuclei with organic molecules in the nanoscale range of 1–10 nm and are typically composed of atoms from groups II–VI (e.g. CdTe, CdSe) and III–V (e.g. InP, InAs) of the periodic table [1]. Their optoelectronic properties change as a function of both shape and size. Colors like orange and red are emitted by larger QDs with diameters of 5–6 nm. QDs with shorter wavelengths (2–3 nm) produce colors such as blue and green [2]. Depending on the exact composition of the QD, the specific colors vary. It is fairly common for these QD cores to be capped with an inorganic layer to boost their quantum yield, which enhances their signal-to-noise ratio [3]. As a result of the size and composition of QDs, they can emit various wavelengths, ranging from ultraviolet (UV) to visible to near-infrared (NIR) [4]. The properties of QDs are intermediate between those of bulk semiconductors and those of discrete atoms or molecules. A hydrophilic material (e.g. mercaptopropionic acid (MPA) or cysteamine) must be added to QD surfaces in order to increase their water solubility [5]. Surface conjugations with synthetic polymers such as polyethylene glycol (PEG) are often useful for preventing aggregation of these nanoparticles [6].

With their unique electronic properties and tunable emission spectrum, quantum dots have attracted considerable interest owing to their resistance to photobleaching, broad excitation wavelength, and high quantum yield [7, 8]. Various applications and devices benefit from the unique characteristics of QDs, including solar cells, fluorescent probes, optical switches, and light sources [9, 10].

The quantum dots can be divided into core-shell QDs, doped QDs, and nuclear QDs in terms of structure. Quantum dots can also be easily modified by encapsulating the surface with amphiphilic ligands, salinizing, and exchanging ligands, further expanding their sensor applications [11–14].

Biosensors can be developed using quantum dots (QDs) [15, 16]. Molecular QDs provide researchers with the ability to study cell processes at the molecule level and may be helpful in diagnosing and treating diseases such as cancer [17]. It is possible to use quantum dots as active sensors in high-resolution cellular imaging, by changing their fluorescence properties as they react with the analyte, or by conjugating antibodies to the surface of the dots to act as passive label probes. Due to the presence of highly toxic heavy metal elements such as cadmium in QDs, these materials cannot be used in biomedical applications [18]. Environmental pollution and toxicity have been a concern in the use of nanomaterials for biomedical applications, and the development of a nontoxic and biocompatible nanomaterial is becoming increasingly important. Incorporating QDs into hybrid nanomaterials has proven easy due to their abundant functional groups [19]. Hybridizing QDs with other materials can provide enhanced thermal and chemical stability, high quantum efficiency, longer excited state lifetimes, and minimized toxicity [20].

The biosensor is a micro-analytical system. As part of the development and application of analytical sensors, biosensing incorporates molecular biological recognition entities [21]. Biosensors are sensing systems that leverage biological recognition to confer molecular specificity to analytes. In the chapter, we first introduce the research trends in the application of QDs and then discuss their surface modification for biological applications.

#### **2. Overview of QDs-based biosensors**

Biosensors have been developed using QDs as promising tools. In **Table 1**, we summarize the selected methods for detecting different targets using various QDs.

Pourghobadi et al. prepared TGA-capped CdTe QDs for the visual determination of the trace levels of dopamine. The fluorescence intensity of the samples was investigated as a result of interaction between TGA-CdTe QDs and dopamine. Fluorescence intensity decreases dramatically with an increase in dopamine concentration. Taking into account this trend, we developed a straightforward method for the detection of dopamine that is sensitive to fluorescence [22].

According to Wang et al., hydrophilic QDs can be used as molecular probes to detect trace amounts of propafenone. Electrostatic attraction and hydrogen bonds allowed propafenone to combine with CdTe QDs modified with thioglycolic acid in the weak acid. Fluorescence, UV-vis absorption, RRS, spectra, and spectral analysis have been used to study the interaction of CdTe QDs with propafenone. With the RRS method, ppb (ng mL−1) levels of propafenone in serum samples can be detected in less than 30 min [23].

Tetracycline was detected in milk using MoS2 QDs and CdTe QDs developed by Liang et al. As a first step, MoS2 QDs emit blue light at 433 nm, while CdTe QDs produce yellow light at 573 nm under 365 nm excitation. We used MoS2 QDs and CdTe QDs to construct a fluorescent sensor with dual signals at 433 nm and 573 nm. MoS2/ CdTe-based sensors show a lower fluorescence intensity as tetracycline concentration

*Recent Advances in Quantum Dots-Based Biosensors DOI: http://dx.doi.org/10.5772/intechopen.108205*


#### **Table 1.**

*Summary of the QDs-based biosensors.*

is increased, and 573 nm is quenched more apparent than 433 nm as tetracycline concentrations are increased [24].

Conjugated CdTe QDs with TGA caps were successfully prepared as a novel biosensor for detecting LPS at concentrations of fg/mL. CdTe QDs showed high crystalline lattice planes with an average size of 4–5 nm in the high-resolution transmission electron photograph. The electrostatic attraction force between positively charged Con A species and negatively charged CdTe QD surfaces was responsible for the adsorption of Con A onto CdTe QD surfaces [25].

The MPA-CdSe QDs were used to detect urea in a case study based on a fluorescence-based "turn-on" probe. MPA-CdSe QDs are sensitive to pH change, and this property makes them useful for detecting urea sensitively and selectively in the presence of urease. By releasing ammonia ions as the enzymatic reaction occurs, the pH of the solution changes, and the fluorescence intensity of the system increases along with the concentration of urea [26].

Researchers conducted experiments to improve the quantum yield of CdTe QDs in 2021 (59.673%). A pH value of 140°C and heating for 40 minutes have been suggested for producing high photoluminescence from CdTe QDs. Salbutamol effectively reduces the fluorescence intensity of CdTe QDs. Fluorescence quenching was linearly related to Salbutamol concentration. Using CdTe QDs as a new fluorescent probe, Salbutamol was successfully measured in pig urine [27].

The main obstacles to their extensive application in biomedicine are their poor biodistribution, low in vivo stability, and high cytotoxicity.

Cd and Se elements in QDs are mostly responsible for their cytotoxicity. The surface conjugations with synthetic polymers such as polyethylene glycol (PEG) are often useful for preventing aggregation of these nanoparticles.

It remains a significant concern about the toxicity of these NPs, despite all the advances in the synthesis of QDs with different coatings. Further research is needed in this area. Researchers are currently working on modifying the surface of QDs to enhance their capacity to capture specific and efficient heavy metals and reduce their release into the environment.

#### **3. Surface modification for biological applications**

To maintain the electronic properties and optical of the core material, one must choose the correct passivating agent when considering real-life applications. Surface ligands play a crucial role in the biological applications of quantum dots. The surface of quantum dots can be easily modified with, metal ions doped, metal-organic frameworks (MOFs), molecularly imprinted polymer (MIP), aptamers, multiwalled carbon nanotubes (MWCNTs), graphene quantum dots and carbon quantum dots, silanization, polymer, and transition metal oxide, which further expands the application of quantum dots in the sensor field.

#### **3.1 Silica**

To encapsulate QDs, silica nanoparticles have attracted considerable attention due to outstanding biocompatibility, high surface-to-volume ratio, ease of functionalization, and low cost. As labels for signal amplification to detect S. aureus, Ag2S QDs loaded onto dendritic mesoporous silica nanospheres (DMSNs) were employed by Wang et al. as electrochemical immuno-biosensors.

As signal-amplifying labels, quantum dots and DMSNs have several advantages. A first step in enriching Ag2S QDs was achieved by taking advantage of high surface area and the extensive pore channels of DMSNs. Each Ag2S/DMSNs signal amplification label loaded with a tremendous amount of Ag2S QDs increased the amount of Ag2S QDs on each S. aureus cell. This resulted in a lower detection limit and a wider detection range for the electrochemical immuno-biosensor. When an electrochemical immuno-biosensor is activated, differential pulse voltammetry can be used to identify S. aureus. From Ab-Ag2S/DMSNs, Ag (I) ions are liberated by leaching with HNO3 [28].

Yang et al. developed a fluorescent probe for the visual detection of folic acid based on silica-coated CdTe QDs nanoparticles. The emission intensity of CdTeS QDs@SiO2 decreased when folic acid was present, and folic acid itself showed fluorescence emission peaks. A gradient color change of nanoparticles was observed with increasing folic acid concentration [29].

*Recent Advances in Quantum Dots-Based Biosensors DOI: http://dx.doi.org/10.5772/intechopen.108205*

For a sensitive NIR immunosensor, Han et al. immobilized CdTe/CdS QDs and antibodies on amino-functionalized SiO2 [30]. Another case involved the modification of Au@SiO2 by CdS QDs [31]. ECL signals were greatly enhanced due to the combination of SPR of Au cores and chemical enhancement from coreactants. SiO2 with quantum dots appears to be a better choice for increasing loading.

CdTe/SiO2 nanoparticles were compared by Shen et al. for their amplification effects (SiO2@CdTe and CdTe@SiO2). This resulted in much stronger ECL emission from CdTe@SiO2 and lower cytotoxicity than SiO2@CdTe, suggesting that bioanalysis of CdTe@SiO2 may prove useful for clinical diagnosis. Compared with solid SiO2, mesoporous SiO2 provided higher loading sites and surface area [32].

In their study, Dong et al. experimented with mesoporous SiO2 as a substitute for solid SiO2. Their results showed that the ECL intensity and stability were much greater on mesoporous SiO2 [33].

#### **3.2 Transition metal oxide**

QDs-based biosensors can also be assembled using transition metal oxides with variable valence states. ECL reaction could be corrected by using transition metal elements as catalysts. In situ activated CdS QDs/TiO2 nanocomposites were used by Dai et al. to develop an enhanced PSA aptamer sensor. As a result of the TiO2 nanotubes' degradation of H2O2 reactants, the CdS QDs were significantly more sensitive to the ECL reaction [34].

Miao et al. immobilized the CdS QDs onto the 3D urchin-like α-FeOOH, realizing ultrasensitive quantitation of 17β-estradiol. In contrast, the Fenton-like process produced more SO4•− radicals through the conversion cycle of Fe3+ and Fe2+, which supported ECL responses through electron transfer [35].

#### **3.3 Metal ions doped**

In recent years, transition metal ions have been investigated as quantum dots because they are not only more efficient than undoped quantum dots, but they also have additional advantages such as chemical stability, longer excited state lifetimes, reduced toxicity, high quantum efficiency, and larger Stokes shift to avoid selfabsorption. The doping of transition metal ions with various impurities such as Sm3+, Mn2+, Zn2+, Ag+ , Gd3+, Tb3+, Cu2+, Er3+, Eu3+, and Co2+ into II–VI QDs has been reported to date. Biological studies can be improved by using QDs doped with cadmium, since they have less toxic cadmium content than their undoped counterparts.

Safari et al. investigated the possibility of using Ni:CdTe d-dots as nanoprobes for the detection of pyrazinamide (PZA) in plasma samples by hydrothermal method with 3-mercaptopropionic acid as the capping reagent **Figure 1**. It has been demonstrated that Ni-doped CdTe QDs have enhanced biocompatibility, photostability, and decreased cytotoxicity when compared to undoped CdTe QDs. For the rapid determination of PZA in plasma samples, a simple, inexpensive, sensitive, and selective method was developed based on fluorescence quenching of Ni:CdTe. Since PZA binds to the surface of Ni-doped CdTe quantum dots, it effectively quenches the emission of the quantum dots [4].

Najafi et al. reported Pd: CdTe QDs by hydrothermal method using palladium ions as a dopant. A linear quenching of fluorescence intensity occurs in the presence of Diazinon. Diazinon was detected in environmental waters using this novel nanoprobe at very high levels of sensitivity and selectivity, as shown in **Figure 2**. Also, the cytotoxicity assay of Pd: CdTe QDs was successfully conducted, which indicates its tremendous potential in biotechnology and medicine [36].

**Figure 1.** *Schematic illustration of PZA detection mechanism using Ni-doped CdTe [4].*

**Figure 2.** *The schematic illustration for Pd: CdTe QDs sensor for the detection of DZN [36].*
