A simple, chip-based implementation of a double-beam interferometer that can separate biomolecules based on size and that can compensate for changes in matrix composition is introduced. The interferometric biosensor uses a double-layer of porous Si comprised of a top layer with large pores and a bottom layer with smaller pores. The structure is shown to provide an on-chip reference channel analogous to a double-beam spectrometer, but where the reference and sample compartments are stacked one on top of the other. The reflectivity spectrum of this structure displays a complicated interference spectrum whose individual components can be resolved by fitting of the reflectivity data to a simple interference model or by fast Fourier transform (FFT). Shifts of the FFT peaks indicate biomolecule penetration into the different layers. The small molecule sucrose penetrates into both porous Si layers, whereas the large protein bovine serum albumin (BSA) only enters the large pores. BSA can be detected even in a large (100-fold by mass) excess of sucrose from the FFT spectrum. Detection can be accomplished either by computing the weighted difference in the frequencies of two peaks or by computing the ratio of the intensities of two peaks in the FFT spectrum.
Strategies to encode or label small particles or beads for use in high-throughput screening and bioassay applications focus on either spatially differentiated, on-chip arrays or random distributions of encoded beads. Attempts to encode large numbers of polymeric, metallic or glass beads in random arrays or in fluid suspension have used a variety of entities to provide coded elements (bits)--fluorescent molecules, molecules with specific vibrational signatures, quantum dots, or discrete metallic layers. Here we report a method for optically encoding micrometre-sized nanostructured particles of porous silicon. We generate multilayered porous films in crystalline silicon using a periodic electrochemical etch. This results in photonic crystals with well-resolved and narrow optical reflectivity features, whose wavelengths are determined by the etching parameters. Millions of possible codes can be prepared this way. Micrometre-sized particles are then produced by ultrasonic fracture, mechanical grinding or by lithographic means. A simple antibody-based bioassay using fluorescently tagged proteins demonstrates the encoding strategy in biologically relevant media.
Elaborate one-dimensional photonic crystals are constructed from a variety of organic and biopolymers, which can be dissolved or melted, by templating the solution-cast or injection-molded materials in porous silicon or porous silicon dioxide multilayer (rugate dielectric mirror) structures. After the removal of the template by chemical dissolution, the polymer castings replicate the photonic features and the nanostructure of the master. We demonstrate that these castings can be used as vapor sensors, as deformable and tunable optical filters, and as self-reporting, bioresorbable materials.
A thermoresponsive hydrogel, poly(N‐isopropylacrylamide) (poly(NIPAM)), is synthesized in situ within an oxidized porous Si template, and the nanocomposite material is characterized. Infiltration of the hydrogel into the interconnecting nanoscale pores of the porous SiO2 host is confirmed by scanning electron microscopy. The optical reflectivity spectrum of the nanocomposite hybrid displays Fabry–Pérot fringes characteristic of thin film interference, enabling direct, real‐time observation of the volume phase transition of the confined poly(NIPAM) hydrogel. Reversible optical reflectivity changes are observed to correlate with the temperature‐dependent volume phase transition of the hydrogel, providing a new means of studying nanoscale confinement of responsive hydrogels. The confined hydrogel displays a swelling and shrinking response to changes in temperature that is significantly faster than that of the bulk hydrogel. The porosity and pore size of the SiO2 template, which are precisely controlled by the electrochemical synthesis parameters, strongly influence the extent and rate of changes in the reflectivity spectrum of the nanocomposite. The observed optical response is ascribed to changes in both the mechanical and the dielectric properties of the nanocomposite.
The fluorescent dye Alexa Fluor 488 or the anti-cancer drug doxorubicin is attached to the surface and inner pore walls of mesoporous Si particles by covalent attachment, and the oxidation-induced release of each molecule is studied. The molecules are bound to the Si matrix using a 10-undecenoic acid linker, which is attached by thermal hydrosilylation. Loading capacity of the microparticles using this method is ∼ 0.5 and 45 mg/g of porous Si microparticle for Alexa Fluor 488 and doxorubicin, respectively. The Si-C-bound assembly is initially stable in aqueous solution, although oxidation of the underlying Si matrix results in conversion to silicon oxide and slow release of the linker-molecule complex by hydrolysis of the Si-O attachment points. When the attached molecule is a fluorophore (Alexa Fluor 488 or doxorubicin), its fluorescence is effectively quenched by the semiconducting silicon matrix. As the particle oxidizes in water, the fluorescence intensity of the attached dye increases due to growth of the insulating silicon oxide layer and, ultimately, dye release from the surface. The recovery of fluorescence in the microparticle and the release of the molecule into solution are monitored in real-time by fluorescence microscopy. Both processes are accelerated by introduction of the oxidizing species peroxynitrite to the aqueous solution. The oxidation-triggered release of the anti-cancer drug doxorubicin to HeLa cells is demonstrated.
Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2-photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose-functionalized pSiNPs can be vectorized to MCF-7 human breast cancer cells through a mannose receptor-mediated endocytosis mechanism to provide a 3-fold enhancement of the 2-photon PDT effect.
We describe the preparation of biodegradable porous silicon nanoparticles (pSiNP) functionalized with cancer cell targeting antibodies and loaded with the hydrophobic anti-cancer drug camptothecin. Orientated immobilization of the antibody on the pSiNP is achieved using novel semicarbazide based bioconjugate chemistry. To demonstrate the generality of this targeting approach, the three antibodies MLR2, mAb528 and Rituximab are used, which target neuroblastoma, glioblastoma and B lymphoma cells, respectively. Successful targeting is demonstrated by means of flow cytometry and immunocytochemistry both with cell lines and primary cells. Cell viability assays after incubation with pSiNPs show selective killing of cells expressing the receptor corresponding to the antibody attached on the pSiNP.
Aim-To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery.Methods-A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology.Results-No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles). Conclusion-The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases.There is an important medical need for a minimally invasive, controllable and monitorable drug-delivery system that would enable long-acting local treatment of intraocular diseases affecting the retina and choroid. In particular, diseases such as choroidal neovascularisation (CNV) in age-related macular degeneration (ARMD), proliferative vitreoretinopathy (PVR) associated with retinal detachment and trauma, and refractory uveitis would benefit greatly. For those chronic refractory diseases, drug delivery to the vitreous, retina and choroid is a challenging task due to the formidable obstacles posed by the blood-retinal barrier and the tight junctions of the retinal pigment epithelium. With systemic administration, only small fractions of drug reach the target, requiring large and potentially toxic doses. An ideal method of retinal drug delivery would provide a locally sustained release for prolonged periods of time. Due to the short vitreous half-life of most injectable intravitreal drugs, frequent administrations are necessary. Intravitreal injection has become standard in clinical practice and trials; however, We have investigated self-assembling liposomes and, most recently, a crystalline drug-delivery material to achieve intraocular long-lasting release of selected antiviral and antiproliferative compounds. 3 4 In particular, the lipid prodrug-delivery system is not feasible for delivery of large molecular compounds such as polypeptides and proteins, which are becoming increasingly important in the treatment of eye diseases. Other systems consisting of biodegradable and bioerodible polymeric microparticles have...
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