Porous silicon in drug delivery devices and materials

A review of experimental work on freezing and melting in confinement is presented. A range of systems, from metal oxide gels to porous glasses to novel nanoporous materials, is discussed. Features such as melting-point depression, hysteresis between freezing and melting, modifications to bulk solid structure and solid-solid transitions are reviewed for substances such as helium, organic fluids, water and metals. Recent work with well characterized assemblies of cylindrical pores like MCM-41 and graphitic microfibres with slit pores has suggested that the macroscopic picture of melting and freezing breaks down in pores of molecular dimensions. Applications of the surface force apparatus to the study of freezing and melting phenomena in confinement are discussed in some detail. This instrument is unique in allowing the study of conditions in a single pore, without the complications of pore blockage and connectivity effects. The results have confirmed the classical picture of melting-point depression in larger pores, and allowed the direct observation of capillary condensation of solid from vapour. Other results include the measurement of solvation forces across apparently fluid films below the bulk melting point and a solid-like response to shear of films above the bulk melting point. These somewhat contradictory findings highlight the difficulty of using bulk concepts to define the phase state of a substance confined to nanoscale pores.

https://iopscience.iop.org/article/10.1088/0953-8984/13/11/201/pdf

Confinement effects on freezing and melting

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.

https://lmrt.mit.edu/sites/default/files/Cunin2002_NatMat.pdf

Biomolecular screening with encoded porous-silicon photonic crystals

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(09)00032-8.pdf

Porous silicon biosensors on the advance

Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.

In vivo targeted cancer imaging, sentinel lymph node mapping and multi-channel imaging with biocompatible silicon nanocrystals.

To use porous silicon as an optical interferometric biosensor, the pores must be sufficiently large to allow easy ingress of reagents and the layer must also display Fabry-Perot optical cavity modes. Here the detection antibody is rabbit IgG and the analyte is α-rabbit IgG conjugated to horseradish peroxidase (HRP). For this model system, the pores should be >50 nm in diameter. Such diameters have been obtained in 0.05 Ω cm n-type silicon using anodisation followed by chemical etching in ethanolic KOH and also by anodising 0.005 Ω cm p-type material. The latter also displays optical cavity modes. The silicon surface is oxidised in ozone, silanised using aminopropylmethoxysilanes with one, two or three methoxy groups, and cross linked to IgG using glutaraldehyde. High specific binding is found for mono-, di- and tri-methoxy silanes, but the lowest non-specific binding is found for silanisation with the tri-methoxy silane.

Tuning the Pore Size and Surface Chemistry of Porous Silicon for Immunoassays

The sensitivity of the optical reflectivity of porous silicon structures to the refractive index of liquid within the pores is studied for a single layer, a Bragg mirror and a microcavity. Sucrose solutions of concentration in the range 0.05 to 1.0% by weight are introduced into the pores within a flow cell in order to change the refractive index of the liquid in the pores from 1.3330 to 1.3344. Optimum wavelengths for detection via reflectivity changes are determined based on a signal to noise analysis. The optical thickness of the single layer is also monitored by measuring the fringe spacing via a Fourier transform technique. It is just possible to detect the effect of a change in refractive index of liquid in the pores of 0.00007 for both the reflectivity and optical thickness approaches.

M. Hollings

Papers

Tuning the Pore Size and Surface Chemistry of Porous Silicon for Immunoassays

Sensitivity of the optical properties of porous silicon layers to the refractive index of liquid in the pores