1/28/2013 Below is an article in the Medical Design Magazine October 2012 edition written by Donna Bibber.
The body thinks in terms of nanometers and so must drug-delivery devices as nanopositioning advancements redefine this product segment.
• Global importance
Ground-breaking methods are bringing us closer to breakthrough devices that “think” like a human body, which when it comes to accuracy, clearly thinks in terms of nanometers (nm) and smaller. These methods are producing 25-100nm tolerances of seal-to-vessel, lid- to-chip, or subcomponent-to-subcomponent in drug-delivery devices.
Why is this important? White andred blood cells range from 8-100 microns (µ) in diameter, and DNA can be as small as 2-3 nm. In between these two ranges are potential for a great deal of discovery and science that we cannot begin to understand without simulation outside the body and by mimicking strands of DNA and blood cells working together.
It is for this reason that drug-delivery and medical and pharmaceutical device companies are looking for help from manufacturers to push the envelope and think outside the box to achieve features and tolerances in the nanometer range. What we have discovered in the micron range has certainly helped us to learn some top down manufacturing methods that don’t work and bottom up methods that do after being refined using a hybrid top down/bottom up method. (See table.)
Growing molecules (using bottom up methods) to create geometry is not something we micro-engineers like to think about, let alone manufacture. We will force that top-down methodology until we can mill, grind, electrical discharge machining, diamond turn, and etch no more. But at some point in the near future, we will all be looking to at least LIGA (German acronym for lithography, electroplating, and molding) as well as different tool-holding mechanisms to create geometry, surfaces, and parts beyond our capabilities in top down methods employed today.
For developing parts with features and tolerances to the singular microns, pallet holders are common tools used to hold and manufacture molds, tooling, fixtures, and components. These can possibly be dialed in to nearly two microns using ultr-precision touch probes in temperature- and humidity-controlled manufacturing environments. To get the nanometer positional accuracy, however, conventional equipment and work-holding pallets cannot be used. As is the case with chasing micron and nanometer tolerances, manufacturers must develop their own methods, fixtures, tooling, and equipment to do the job. Every work-holding fixture and automated end-of-an-arm tool is customized for picking and placing dust-specked size parts.
Drug-delivery devices, parts, materials, and processes that are enabled by nanometer positional accuracy include:
• Powder inhaler mechanisms
• Microfluidic chip/cover assemblies
• Intraocular implant surfaces
• Insulin delivery pumps
• Bio-resorbable polymer thin-walled implants
• Surface coating/masking
• Elusive flashless molding
One of the greatest challenges when achieving micron-to-nanometer tolerances comes in the form of microfluidic chips that are covered with a polymer, adhesive, or membrane lid.
Average microfluidic channels are less than 100µ in width so they can carry red and white blood cells or other fluids without blocking the channels. The velocity by which the capillary action works makes no room for error, which means no room for channel-to-channel cross contamination. The lid or cover must be held in place sometimes on a shelf as small as 10µ in width. It is challenging to accurately position a piece of thin polymer, adhesive, or membrane to this thin surface area to seal the channels and keep them from leaking into one another. This is a catastrophic failure for critical tests such as HIV, TB, or malaria, to name a few.
Another worldwide challenge for wireless drug-delivery devices are MT Ferrules used to generate light and bandwidth for wireless devices. These devices have two 600µ holes with 10-12 125µ holes between them. The very best that can be done using conventional pallet holders is ±2µ as a stack-up tolerance device. With customized nanometer positional assembly holders, this MT ferrule can be made to 100nm positional-accuracy. This leads to an overall product improvement of 15-25% additional light or bandwidth, which can send data faster than ever before to wireless devices, now commonly used by physicians, researchers, and engineers developing drug-delivery devices of the future.
Measuring parts such as the MT ferrule and other wireless devices that are advancing nanometer positional accuracy is also spurring new metrology equipment such as CT scanning to measure parts accurately and in one setup, an absolute critical factor in reducing error in any tiny part or feature manufacturing process.
CT scanning can scan a second or third component or assembly from a top-down view and create a point cloud of data that can then be compared with a nominal solid model. This powerful tool saves countless hours of picking up a part in several planes, creating multiple fixtures to effectively “show” the part to the correct lighting beam, and then repeating this process for each plane required. Again, each time that part is picked up and placed down, another datum plane is required that may or may not be able to link to the previous datum. This can be a challenging and error-prone “stitching” process.
Nontraditional methods for manufacturing such as nanometer positional accuracy and dust specked-sized injection molded, machined, and assembled components are spawning many new products for drug-delivery device companies as the healthcare community continues to battle chronic conditions, such as diabetes and glaucoma, while delivering vaccinations to third-world countries.