NANOTECH REDEFINES THE WAY DRUG-DELIVERY DEVICES ‘THINK’
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.
ARTICLE FOCUS
• Methods
• Challenges
• 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.)
Method
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
Challenges
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 (see Figure 2) 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. (See Figure 3.). 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. (See Figure 1.)
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.
Global weapon
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.
MICRO helps save the environment by increasing battery life with peel-and-stick solar cells!
1/22/13 An alarming statistic I heard on the radio the other day…… We, as Americans consume nearly 60 BILLION batteries a year. 60 BILLION! If that doesn’t deserve a “there’s gotta be a better way”, I don’t know what does. In our micro manufacturing world of electronics, micro molded medical devices that monitor, measure, and/or wirelessly transmit, many are powered by battery and will be in the future.
Many micro and nano technology platforms are currently in research to improve battery life, create flexible batteries, and place them on micro substrates that are resistance to moisture, heat, and extreme environments. This article reflects some of the fabulous work being done to save the environment, provide increased battery life and space-saving, contoured fitting to devices.
NREL and Stanford Team up on Peel-and-Stick Solar Cells – devices could charge battery-powered products in the future
(January 10, 2013 article)
It may be possible soon to charge cell phones, change the tint on windows, or power small toys with peel-and-stick versions of solar cells, thanks to a partnership between Stanford University and the U.S. Department of Energy’s National Renewable Energy Laboratory (NREL).
A scientific paper, “Peel and Stick: Fabricating Thin Film Solar Cells on Universal Substrates,” appears in the online version of Scientific Reports, a subsidiary of the British scientific journal Nature.
Peel-and-stick, or water-assisted transfer printing (WTP), technologies were developed by the Stanford group and have been used before for nanowire based electronics, but the Stanford-NREL partnership has conducted the first successful demonstration using actual thin film solar cells, NREL principal scientist Qi Wang said.
The university and NREL showed that thin-film solar cells less than one-micron thick can be removed from a silicon substrate used for fabrication by dipping them in water at room temperature. Then, after exposure to heat of about 90°C for a few seconds, they can attach to almost any surface.
Wang met Stanford’s Xiaolin Zheng at a conference last year where Wang gave a talk about solar cells and Zheng talked about her peel-and-stick technology. Zheng realized that NREL had the type of solar cells needed for her peel-and-stick project.
NREL’s cells could be made easily on Stanford’s peel off substrate. NREL’s amorphous silicon cells were fabricated on nickel-coated Si/SiO2 wafers. A thermal release tape attached to the top of the solar cell serves as a temporary transfer holder. An optional transparent protection layer is spin-casted in between the thermal tape and the solar cell to prevent contamination when the device is dipped in water. The result is a thin strip much like a bumper sticker: the user can peel off the handler and apply the solar cell directly to a surface.
“It’s been a quite successful collaboration,” Wang said. “We were able to peel it off nicely and test the cell both before and after. We found almost no degradation in performance due to the peel-off.”
Zheng said the partnership with NREL is the key for this successful work. “NREL has years of experience with thin film solar cells that allowed us to build upon their success,” Zheng said. “Qi Wang and (NREL engineer) William Nemeth are very valuable and efficient collaborators.”
Zheng said cells can be mounted to almost any surface because almost no fabrication is required on the final carrier substrates.
The cells’ ability to adhere to a universal substrate is unusual; most thin-film cells must be affixed to a special substrate. The peel-and-stick approach allows the use of flexible polymer substrates and high processing temperatures. The resulting flexible, lightweight, and transparent devices then can be integrated onto curved surfaces such as military helmets and portable electronics, transistors and sensors.
In the future, the collaborators will test peel-and-stick cells that are processed at even higher temperatures and offer more power.
NREL is the U.S. Department of Energy’s primary national laboratory for renewable energy and energy efficiency research and development. NREL is operated for DOE by the Alliance for Sustainable Energy, LLC.
MICRO MACHINING COMPONENT PRODUCT DEVELOPMENT
1/16/13 Micro Engineering Solutions is an expert in the field of micro machining. Our product development has included silicone valves, transdermal patches, insulin delivery pump assemblies and a variety of micro implants. View our micro machining video for more details.
2012 MICRO BLOG IN REVIEW
1/4/13 With 2012 behind us we wanted to review the interesting and informative blogs we have written over the past year. They are full of useful information and videos and deserve repeating! Please click on any of the below blog titles to see the blog.
MICRO MOLDING:
– Micro Computational Analysis
– Micro Molding Intraocular Implants
– Global Healthcare Industry is Going MICRO
– Micro Molding Using Bio-Resorbable Polymers
– Micro Molding Needles and Sharps
– Fast Dissolution Rate Polymers
– Micro Molded Valve Technology
– Challenges in Micro Molding with Bio-Resorbables
MICRO MACHINING:
– Use of Microscopic Surface Finish in Scaling Precision Medical and Pharmaceutical Devices
– Drug Delivery and Point of Care Device Collaboration
– Micro Machining Validation using CT Scanning
– PEEK Micro Machining Cost Effectiveness
MICRO ASSEMBLY:
– Micro Medical Devices using Electrical & Magnetic Stimulation
– Neuroscience Devices Enabling All of the Senses
– Micro Manufacturing is on the Rise
MISC:
– Partnership in Drug Delivery Conference Hi-lights
– Micro Research is Leading the Way for New Technology
– Micro Features in Polymer Parts can Control Biological Activity in Cells
MICRO FEATURES IN POLYMER PARTS CAN CONTROL THE BIOLOGICAL ACTIVITY IN CELLS
1/2/13 When it comes to bioengineering, microfeatures in polymer parts are used to control the biological activity of cells, letting us analyze their mechanical behavior with its surround environment. Cells can turn a mechanical cue into an internal chemical signal to initiate migration. We are able to provide cell therapy due to this control on the cells. Temperature plays a significant role in this process. An experiment was done at Lehigh University to test this using a silicone polymer wafer. The conclusion of this test showed that altering mold temperature and material can potentially achieve microstructures with increased aspect ratios. It found that pillar height increased as a function of mold temperature. They concluded that more testing needs to be done to determine optimum conditions to ensure filling and proper demolding of the polymer pillars. With this testing, it is believed that a variety of surface compliances can be created and used to direct biological cell activity.