Mechanism of optical biosensors
For optical sensors, different types of mechanisms involving energy transfers are involved such as Forster Resonance Energy Transfer, Fluorescence Energy Transfer, Resonance Energy Transfer, or Electronic Energy Transfer (Chang and Park 2010). Theodor Forster developed this technique where the mechanism influences energy transfers between two light-sensitive molecules. The energy transfer mechanisms involve when a donor chromophore is in its high excitation state and energy is transferred to the acceptor chromophore through dipole–dipole interactions (Chang and Park 2010; Orazem et al. 2011). The criteria for the stated energy mechanisms involve the distance between the donor and acceptor chromophore, and the orientation of the chromophores. The methods used in these energy transfers help in identifying how surface modification will take place. The FRET mechanism is between two fluorophores used as donor (D) and acceptor (A). The energy transfer efficiency (E, i.e., the fraction of energy transferred) is reverse proportional to the distance of two fluorophores as shown in Eq. 2.
$$E = \frac{1}{{\left[ {1 + \left( {\frac{r}{{R_{o} }}} \right)^{6} } \right]}},$$
(2)
where r is the distance between two fluorophores and R
0 the distance at which 50% E was achieved. R
0 is a characteristic parameter for given partners at given medium.
Chemiluminescence Resonance Energy Transfer (CRET) is another technique used when non-radiative energy source is used to transfer energy from the donor chromophore to the acceptor chromophore. Chemiluminescence (CL) is one of the techniques implemented to generate electromagnetic radiation by which the excited product initiates back to its original state before the excitation. Using the CRET methods, immunosensors can be established in receptiveness to the C-reactive protein (CRP) levels. CRP measure levels can differentiate between the normal and serious conditions. (Gupta et al. 2014; Masters 2014; Beljonne et al. 2009; Zhu 2015; Huang et al. 2006). This is one of the other unique techniques implemented on the surface modification on graphene oxide or graphene.
The other technique implemented to explain the use of the optical sensors is the photothermal therapy, often referred to as PTT. It uses electromagnetic radiation within the infrared region to treat medical conditions, such as the elimination of the tumor cells. Using PTT has better advantages than using PDT as oxygen is not involved to interact with the target cells or tissues and lower energy is used, thus minimizing the cytotoxicity of the cells. Photothermal therapy has been a novel technique in eliminating the defects of chemotherapy (Chen et al. 2016).
Design of graphene-based optical probe for cancer cell detection
Here, we are focusing on two major optical biosensors, i.e., Fluorescence Resonance Energy Transfer (FRET), Chemiluminescence Energy Resonance Transfer (CRET).
FRET and CRET are non-radiation fluorescence. The distance-dependent energy resonance transfer between donor and acceptor makes them offer great benefits in accurately detecting biomolecules/cells in vivo and in vitro.
Fluorescent amino acid (histidine)-functionalized perylenediimide (PDI-HIS) is a technique where the “turn-off and turn-on” can detect Cu2+ ions. The disaggregation of PDI-HIS-Cu2+ of the fluorescence quenching helps detect the PPi levels (Muthuraj et al. 2015).
A unique optical approach on detecting the concentration of pyrophosphate (PPi) has a direct correlation with the cancer diagnosis. The fabrication technique of using the fluorescent probe of PDI-HIS, copper ion, and graphene oxide (GO) which enhances the selectivity and sensitivity for detecting PPi, a cancer biomarker (Muthuraj et al. 2015). The results show that the self-assembled nanocomposites made of PCG (PDI-His + GO + Cu2+) have a low detection limit (LOD), 1fM, for PPi in comparison to PDI-HIS-Cu2+.
The B16F10 cells were used with GO-based composites to detect the concentration of PPi. After incubation time, the B16F10 cells treated with 300 μg mL−1 of PDI-HIS give a red fluorescence. The addition of Cu2+ and GO will quench the fluorescence. PCG is much more sensitive in detecting the level of PPi than only PDI-HIS + Cu2+ (Muthuraj et al. 2015).
The overexpression of MUC1 has been noted in cancer cells with regard to features associated biochemically and functionally (Papadimitriou et al. 1999). MUC1 consists of MUC1-N and MUC1-C regions where MUC1-N is composed of proline, threonine, and serine-rich domain. In the mitochondria and nucleus, there is a detection of MUC1-C in the mitochondria and nucleus, whereas MUC1-N is detected in the nuclear speckles as shown in Fig. 5. Looking at a comparison between a normal epithelial cell and a cancer cell, one can distinguish that the tumor cell has lost its polarity where the and the increased expression of the hypoglycosylated form of MUC1 (Yu et al. 2015; Yang et al. 2013; Nath and Mukherjee 2014; Pouilly et al. 2000; Beatson et al. 2010; Mukherjee et al. 2003; Bitler et al. 2009; Sahraei et al. 2012). MUC1 is present on the surface of the tumor cells, close to the growth factors surrounding it (Chen et al. 2015). Antichemotherapy drugs are inaccessible to the targets as the glycosylated MUC1 inhibits from reaching its targets. MUC-1 has a correlation with the increase in tumor cells related to breast, ovarian, colon, lung, and prostatic cancers (Chen et al. 2015). The new novel immunotherapy instigated that the increase in MUC-1 would have to diminish by attaching it to the NK cells which makes this an anticancer method (Yu et al. 2015; Yang et al. 2013; Nath and Mukherjee 2014; Pouilly et al. 2000; Beatson et al. 2010; Mukherjee et al. 2003; Bitler et al. 2009; Sahraei et al. 2012).
In addition, FRET technique by utilizing quantum dots for the chemotherapy of ovarian cancer has been reported. The FRET technique transfers energy to the drug molecule from the quantum dot (QD) as they are attached on graphene. The fluorescence emission was recorded and the quenching indicates the release of doxorubicin (DOX) from QD. A more innovative modified structure shown in Fig. 6 exhibits high anticancer efficiency by conjugating DOX on to the QD modified with a glycoprotein, e.g., MUC 1 which realizes the targeted delivery (Savla et al. 2011). Some reports show that graphene or graphene oxide-based FRET sensor incorporating the design with antibody-DNA-Au NP can be used for detecting cancer cells (Jung et al. 2010).
CRET techniques apply luminescence organic chemicals to excite an acceptor in CRET pair. The graphene-based CRET sensor has been developed for detecting the interaction between anti-C-Reactive Protein (CRP) and the C-Reactive Protein (CRP). Such immune sensor can accurately detect the C-reactive protein level. The amount of CRP with respect to the normal levels is usually less than 3 mg L−1. The concentration of CRP significantly increases when there is an infection associated with cardiovascular disease, in this case, the primary issue is focused towards Lymphoma Cancer. Higher CRP concentrations have been reported towards lung, pancreatic, breast, ovary, esophagus, liver, biliary tract, stomach, and multiple myeloma (Heikkila et al. 2007).
The new stepping stone of surface-modified Apt-PBMC and the CRP-capturing ability is examined (Hwang et al. 2016). The new innovation which drives as a stepping stone fluorescence imaging towards the detection of CRP has been examined. The new surface-modified engineering application is a new innovative idea towards cancer treatment. The Apt-PBMC complex had a recognition towards different concentrations of CRP and had an impact towards the fluorescence intensity levels. As the concentrations of the CRP increased, the fluorescence intensity increased (Hwang et al. 2016).