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Materials fabrication processes for biomedical applications

Biomedical devices such as sensors and drug delivery patches pose an interesting challenge in material fabrication due to stringent requirements of substrates, thermal budgets etc. This post outlines five examples from literature of plasma and thermal processes done on Oxford Instruments Plasma Technology tools used for applications in healthcare.

  1. ZnO nanowire sensors fabricated using ALD and Ion Beam Etching processes1

Researchers at University of Southampton have developed a pH sensor with sensitivities down to 46.5 mv/pH.  The device is fabricated using an Atomic Layer Deposition (ALD) process for the  ZnO layer which is then anisotropically etched into 40 nm nanowires. The process is scalable up to 6” wafers and uses standard photolithography techniques.

  1. ALD deposited ZnO based drug release layers2

The laboratory of biomedical microtechnology (IMTEK) at University of Freiburg have deposited ZnO directly into a film of Poly ethylene glycol which forms the matrix for the release material. They deposit a conductive polymer on top of this layer which changes its permeability based on electrical stimuli. They observe the controlled release using fluoroscein.  Here the key requirement was the <150 ⁰C thermal budget for the ZnO deposition. Using an OpAL system the researchers were able to deposit ZnO at temperatures as low as 50 ⁰C.                                                                                                                                

ALD –ZnO based drug release layers (inset shows fluroescence microscopy image of electrically stimulated release of fluorescein)2 (licenced under CC BY 4.0)
ALD –ZnO based drug release layers (inset shows fluroescence microscopy image of electrically stimulated release of fluorescein)2 (licenced under CC BY 4.0)
  1. Si microneedles for drug delivery patch applications

Oxford Instruments Deep Reactive Ion Etching (DRIE) processes have been extensively used for the fabrication of high aspect ratio needles for applications in transdermal delivery of drugs or sub micrometer needles for intracellular interfacing as demonstrated by scientists at University of Washington at Seattle3. In this process an RIE process is used to sharpen a 230 μm silicon pillar to a width of 200 nm at its tip. They encapsulate individual needles in a polyimide support structure to demonstrate a flexible neural implant device.

  1. Protective dielectric layer to preserve femtomolar sensitivities of SOI nanowire biochips4

Plasma enhanced ALD processes were used by researchers at Russian academy of sciences to demonstrate that coating the Silicon nanowire sensors with amorphous alumina has no detrimental effect on the sensitivity of these devices and provides the added benefit of improved stability in liquids.

  1. Biomolecular detection using electrically excited plasmonic nanoparticles5

In a collaboration between the department of nanobiophotonics and department of quantum detection at Leibniz Institute of Photonic Technolgy at Jena, Germany scientists have demonstrated electrically excited plasmon modes using  a metal-dielectric-semiconductor  heterostructure.  ALD was used to deposit the Al2Odielectric layer that acts a the tunnel junctions which upon application of a voltage across it generates surface plasmons based on the fluctuations of the tunnelling current.  Using this technique they demonstrate bio-detection using bovine serum albumin (BSA) which forms recognition layer on the metal nanoparticles. Then an analyste consisting of antibodies that specifically bind to BSA (anti-BSA IgG) were detected using the spectral shift caused by the binding of these biomolecules.

References:

  1. Sun et al. Microelectronic Engineering 153 (2016) 96–100
  2. Boehler et al., Scientific Reports6, 19574 (2016)
  3. Hanein et al., J. Micromech. Microeng. 13 (2003) S91–S95
  4. Popov et al., Semiconductors, 50,(2016) 5, 632–638
  5. Dathe et al, Nano Lett. 2016, 16, 5728−5736

Author: Dr Ravi Sundaram