Quantum Dots

Biochemical Application

Introduction: Quantum dots are a system of elements that confine the charge carriers in a potential well. The system is analogous to a 3-dimensional well, where energy is zero everywhere inside the well and infinite on its walls. When the dimension of a crystal becomes less than the de Broglie wavelength, the crystal shows highly quantized characteristics. More so in semiconductors than metal. That is why usual quantum dots has a semiconductive element in the core and the size is 10 - 100 nm(1). For a spherical well with diameter d, the lowest energy state of the well is, E = h2/2md2. Here h is the plank constant and m is the mass of the charge carrier. When a electron-hole pair is generated in the quantum dot the required energy is, Eg = Eg(bulk) + Ewell + Ecoul, here, Eg(bulk) is the energy gap between a electron-hole pair in bulk material and Ecoul is the electrostatic energy of a electron-hole pair. The coulomb interaction takes into account the electrostatic interaction of an electron-hole. An estimate of the coulomb term is shown below, Ecoul = - 1.8e2 / 2od, here e represents the charge of an electron. Based on these estimations the energy gap of a spherical quantum dot is, Eg = Eg(bulk) + h2/2md2 - 1.8e2 / 2od (2) The above relationship ignores the crystal anisotropy and the spin- orbit coupling to simplify the calculation. The size dependency of QDs are apparent from the above equation. By manipulating the nanocrystal size the absorption and emission spectra of the QDs are manipulated as shown in figure 1.

Figure 1: The size dependance of emission spectra of QDs are presented here. Synthesis: The most common preparation of QDs is an organometallic approach introduced by by Murray et al. in 1993. The preparative route is based on the pyrolysis of organometallic reagents (like dimethylcadmium and bis(trimethylsilyl)selenium) by injection into hot coordinating solvents (like trin-octylphosphine oxide (TOPO) and tri-n-octylphosphine (TOP)). This provides temporally discrete nucleation and permits the controlled growth of nanocrystals. The size distribution of the crystals could be further reduced by size-selective precipitation. Using this synthesis process uniform high quality QDs could be synthesized with reproducibility. The synthesis process is shown in figure 2 (3). Later the TOPO layer is replaced or modified with surface molecules that give the QD to dissolve in water and link with biomolecules.

Figure 2: High-temperature coordinating solvent synthesis of colloidal CdSe quantum dots. For a typical reaction, a three-necked flask is placed in a heating mantle and equipped with a thermocouple and temperature controller. A cadmium precursor (e.g. cadmium oxide or cadmium acetate) is dissolved in the tri-n-octylphosphine oxide (TOPO) coordinating solvent in an inert atmosphere (argon or nitrogen flow).Under continuous stirring at high temperature (~320oC), a selenium precursor dissolved in tri-n-octylphospine (TOP) is swiftly injected into the flask, initiating rapid nucleation of CdSe nanoparticles.

Biochemical Application: QDs are mostly used as a substitute of organic dyes. Due to intense fluorescence, high quantum yield and photostability, they are the choice for sensitive bioanalytic experiments. The early use of QDs started as a label for DNA hybridyzation, immunoassays, binding assays etc. The biggest advantage of QDs are the sharp narrow emission and absoption spectra. As a result of this multiple QDs with different color spectra could be used to detect multiple targets with a single light source (4). QD were used as sensor for Frster (Fluorescence) resonance energy transfer (FRET) experimentation. A photoactivated switch was used for the acceptor instead of the traditional spatial reorganization of donor-acceptor pair. This finding could be useful in determining the orientation of proteins in other hybrid proteinnanoparticle materials(5). Due to their high photostability perhaps the most important application of QD could be as a florescence label for in vivo experiments. Organic dyes could not be used as near infrared they are

photounstable and auto-fluoregenic. By tuning the semiconductor core of the QD, it could become a usable label at near infrared region. Also the superior photostability and high quantum yield gives QD the advantage in vivo screening. Specific cell receptors could be targeted by using peptide conjugated QDs. Using near-infrared tuned QDs, rats coronary vasculature as well as porcine sentinel lymph nodes with a tissue penetration depth up to one centimeter was imaged (6). Another interesting use of QDs are optically encoded polymer photospheres. These were used to high high-throughput genes, proteins screening. The QDs were encapsulated in a polymer bead, with a specific spectroscopic signature. This identifies the particular biomolecule attached to the bead (7). Future Application: In the light of present applications, QDs could be used as smart nano-sensors for various target analytes. Complete organ imaging could be another possibility. Perhaps the most important application could be in cancer treatment. QDs conjugated to peptides have been intravenously injected into mice for targeting specific endothelial cell receptors in lung, tumor blood vessels and tumor lymphatic vessels. As a result accumulation of QDs in the targeted tissue was observed. Now if selective excitation of accumulated QDs could produce enough energy to kill the tumor cell, it would present a better alternative to radiotherapy. Conclusion: QDs are extremely versatile and efficient. The problem using QDs now are, expense, availability. Once these shortcoming are addressed, new and exciting biotechnological advance would be possible. References: 1. Reed MA; Hornbeck, ES; Deshpande, MR; Wheeler, RG; Reed, MA; Bowen, RC; Frensley, WR; Randall, JN et al. (1993). "Quantum Dots" (PDF). Scientific American 268 (1): 118. 2. Norris, DJ; Bawendi, MG (1996). "Measurement and assignment of the size-dependent optical spectrum in CdSe quantum dots". Physical review B 53 (24): 1633816346.

3. Murray CB, Norris DJ, Bawendi MG (1993). "Synthesis and characterization of nearly monodisperse CdE (E = S, Se, Te) semiconductor nanocrystallites". J Am Chem Soc 115 (19): 870615. 4. A.R. Clapp, I.L. Medintz, J.M. Mauro, B.R. Fisher, M.G. Bawendi, H.Mattoussi, J.Am.Chem. Soc.126 (2004) 301. 5. D.M. Willard, L.L. Carillo, J. Jung, A. Van Orden, Nano Lett.1 (2001) 469. 6. B. Dubertret, P. Skouride, D.J. Norris, V. Noireaux, A.H. Brivanlou, A.Libchaber, Science 298 (2002) 1759. 7. M.Y. Han, J.X. Gao, J.Z. Su, S. Nie, Nat. Biotechnol. 19 (2001) 631.