To get this article head over to Biocoat’s hydrophilic coating article page, and request a copy. This is a must read for those seeking to a develop medical device with a lubricious coating.

A similar article by Biocoat will be printed in MDDI Magazine this May. The online version already appears here.

As I understand them, the basics of microfuidics are this. For a given device application, there is a requirement that tiny amounts of fluid get sucked up or routed through tiny channels made of plastic, usually through capillary action. As you might guess, surface energy of the polymer plays a big part in how easily the fluid moves through them. Coating a chamber with a hydrophilic coating will lower that surface energy, and allow for increased capillary action. Simple, right? Hey, let’s slap a coating on that and crank out some devices tomorrow, shall we?

Hold on a moment. Not all microfluidic applications are equal, and all of them are challenging when it comes to coating. Let’s look at some of the challenges.

1. “My channels are 3 microns wide and 15 cm long.” – Most hydrophilic coatings are applied by directly wetting the surface with the coating solution and then curing and drying it somehow. While it is true that there are some coatings out there that can coat a channel that is 3 microns wide, there is always the possibility with most coatings that the coating liquid will plug up the channel and clog it. Additionally, it is not only about width… it is also about channel length. Longer channels are more difficult to wet with the coating solution. Short channels have a better chance, but still have great risk of clogging with most hydrophilic coatings out there.

2. “My substrate material is XXXX, which will require plasma treatment… and my channels are 3 microns wide and 15 cm long.” – Remember, not all coatings stick to all surfaces. For example, to coat silicone, many hydrophilic coatings will require that you plasma treat the silicone before the coating will adhere. That is easily done if the surface is flat and open to the air, but when the surface is the inner diameter (ID) of a tiny channel, how do you expect to get the plasma inside to treat the surface? If your surface requires plasma treatment to get that coating to stick, you either need to look for a different coating, forget about a coating, or think about changing your substrate material to something that requires no pre-treatment.

3. “My device is exposed to temperatures of 100C under water for 5 years.” – Here’s something about hydrophilic coatings that I wish everyone knew: they degrade and/or delaminate in water at high temperatures. I don’t care what the coating is made from, all hydrophilic coatings have some similar principles in common. They all absorb a lot of water. They all either have a primer coat (that can absorb some water) or they are a single coat that absorbs a lot of water. At high temperatures, especially above the Tg of the polymer, water will infiltrate the primer coat or the single coat and plasticize the polymer further, causing greatly decreased adhesion. If there are no hydrolysis reactions eating away the coating (and that is a BIG if), the coating will eventually just float away. By “eventually”, I mean it will happen anywhere from instantly to not long after that…. certainly not over a period of 5 years, or even 1 day. (I haven’t actually done a degradation study of every hydrophilic coating out there, so I can’t be more specific.) If you ask to coat microfluidic channels, or any device really, the moment you say “water” and “100C”, it’s all over. Find some other way that does not involve a hydrophilic coating.

4. “Great, the coating works! Now how do we manufacture coated devices with it?” – This is a good question. Too often, there is not enough consideration given to whether or not something will be a nightmare to manufacture. Just because the technology works does not mean it is easy to make on any large scale, or even possible to make on a large scale. Start thinking about this early. Microfluidic devices would require highly specialized equipment to coat, and chances are that equipment would need to be designed, built, validated, etc. from scratch. That takes time.

Honestly, if two potential clients come to me and one has a 3 Fr catheter OD and the other has a microfluidic plate with 1-mm channels made out of PVC, I get a lot more excited about the former. The latter is a lot of effort with a very low chance of success.

As a side note, I am actually surprised at the lack of information on medical hydrophobic coatings on the Internet. There is certainly some, but no one to speak of has really dominated the search engine rankings on that subject. Compare that to the three or four companies duking it out over hydrophilic coating terms.

Hydrophilic Coatings: Considerations for Product Development

HYDAK® HydroSleek coatings are based on a high molecular weight Hyaluronic Acid (HA). This technology has applications among a range of fields including ophthalmology, urology, cardiology, endoscopy, and neurovascular. HydroSleek coatings have overcome the trade off between lubricity and durability seen in cross-linked coatings. Additionally, HydroSleek involves a heat-cure process so both ID and OD may be coated without the concerns surrounding UV curing.

This new product will act as Biocoat’s front line solution to medical device firms seeking to reduce surface friction for their devices. HydroSleek possesses the same beneficial characteristics of the family of HYDAK® coatings, plus advancements device manufacturers have requested.

Another reason why I like this show is it gives me a chance to visit with my hydrophilic coatings “family”, that somewhat incestuous tightly-knit group of competitors which all sell hydrophilic coatings among other things. It was good to see everyone again and to meet some people with whom I have not yet had the pleasure. My impression is that this business suffers a little bit from ADD in that few companies make their living only from hydrophilic coatings. (Perhaps because that is tough to do when the revenue from them can be small at times. Even my own company dabbles in the fertility industry.) All of these companies do hydrophilic coatings…. and something else. It is fascinating to see what their other ventures are: plasma treatment, biomaterials development, chemicals, contract manufacturing, contract manufacturing equipment, and others.

Beyond that, I like to see what the medical device companies are doing, and to find out more about why they are using lubricious coatings for their surfaces. I learned a lot of new information about catheters, guidewires, and some less common devices on this trip. Looking forward to servicing the new leads and seeing where they…. lead.

Granted, this is a grim view and an extreme black-and-white example.  The truth is more gray.  Yes, some universities may ultimately create things that get sold on the market and wind up being profitable, many years from now.  It is nice to get in on the ground floor on some of these things.  Some hydrophilic coating companies might!  In fact, some companies have partnerships with universities that do that very same thing.  These companies contribute funding to research done on coatings, and somewhere, there’s probably at least one happy grad student in each of those labs getting funded.  It’s always good when that happens.  This is coming from me, a former corporate-funded grad student.

However, not all hydrophilic coating companies will.  There are several reasons:

1)  $ – I mentioned this above.  It’s just not worth it monetarily.

2)  IP – Universities tend to be a little “grabby” when it comes to IP.  When doing anything with a university, you need a contract to lay it all out first, and usually the first draft of that contract says “All your invention are belong to us”.  (Only true geeks will get the bad grammar reference there.)  As a hydrophilic coating company, this is completely undesirable.

3)  Time – A university can sometimes require as much time and attention as a normal corporate client, but for what return?  See reasons #1 and #2.

That’s really it.  Those are the three reasons.  So, the key here if you are a university researcher is to find a company that deals with universities, and also to find one that is open to new dealings with universities.  Some companies pair up with one or two schools and that’s it.

I would say the large majority of hydrophilic companies either have a deal already in place or do not deal with universities.

Here is my beef:  I see it commonly.  A hydrophilic coatings company will “whip up” a coating and put it on the market.  Putting it on the market is not a problem.  “Whipping it up” is, especially when the company goes on to make all kinds of ridiculous marketing claims about it, many of them patently false or unproven.  I wish the Federal Trade Commission (FTC) would take a look at some of these claims, honestly.  As a generic example, “XXXX is the most lubricious coating available.” or “XXX enhances the design features of any device.”  These sorts of claims often come from companies that never show testing data beyond 10 cycles.  Anyone can do that.  Essentially, these claims are made without any meaningful data to back them up.

This is just one example.  Others exist.  Another example is when companies take a hydrophilic coating, dump an antimicrobial into it and mix it together and just because it mixes successfully the company touts the coating as an “antimicrobial hydrophilic coating”.

So, why do I have a problem with these practices?  Two reasons:  a client can really hose itself by going to one of these companies and then finding the coating is completely untested and probably never would have worked in its application.  Time is wasted.  Second, it ruins it for the other hydrophilic coatings companies that do the right thing and put their coatings through extensive verification testing BEFORE putting them on the market.  Coatings that are done right have a better chance of success because their vendors are more knowledgeable of how they will perform under certain applications.

Now let me get specific.  In my opinion, for a coating to be released to market for use in medical devices, the vendor must have some idea that it will work in at least some intended applications, and most medical applications have certain things in common like shelf-life determination and sterilization.  That means certain tests need to be conducted on the coating before trying to  release it to market:

1)  Lubricity and durability baseline – What is the coefficient of friction and how many cycles can the coating withstand initially after applying to a surface?  Sure, you can show 10 cycles with a tiny normal force, but know that the best coatings out there can bury you if you do that.

2)  Lubricity and durability after sterilization – If you are going to say your coating is sterilizable, then you darn well better actually sterilize it and see if it is.  For every method you claim, you need to do a test for it:  Gamma-irradiation, Ethylene Oxide, Autoclaving, Other, etc.  How much lubricity/durability does it lose?

3) Lubricity and durability after Aging AND Sterilization – It’s nice if your coating can be sterilized every which way, but what happens if you sterilize it and then stick it on a shelf for three years?  Will it function after that?

These are just some items to look at.  Other things could include a knowledge of what substrates work best with the coating, an Arrhenius Plot of degradation at different temperatures, a study of the coating solution aging characteristics, and more.  That is what it means to know a little about a coating, but barely scratches the surface.

Antimicrobial coatings have it worse.  Probably 90% of the antimicrobial hydrophilic coatings out there are untested.  Their creators just mixed them up and got them to mix successfully and put them right out into the field.  If I were a buyer, I’d be scared.  What is the release profile of the antimicrobial from the coating?  What is the primary method by which it kills?  What organisms does it target?  For how many days does it release?  Most importantly, does the addition of the antimicrobial affect any of the other four things I talked about above: lubricity, durability, sterilizability, and aging of the coating?  What happens if you store the coating solution containing the antimicrobial?  Remember, the “product” sold by the hydrophilic coating company is usually a bottle of liquid coating solution, not a dry coating on a finished device.  Has the hydrophilic coating company done sufficient shipping tests, aging, and pot life characterization of its product?  The answer for most of these companies is a resounding “NO”, and that is why I am not pleased, on one hand.

On the other hand, the companies that are doing this right, but taking a little longer to get to market, will have a business 5 years from now.

Today I want to point out two possible roads you can take when manufacturing medical devices with hydrophilic coatings.  Both have their own advantages and disadvantages.  On one hand, you can do the less automated approach.  This involves having one or more dipping/spraying/other coating machines in a clean room, operated by a tech at each machine.  The operator(s) load(s) each device into the machine manually and, if necessary, unmounts the devices and moves them on a cart to the next machine/oven/etc.  Alternatively, you can have a more automated process, whereby an operator puts the devices in at one end, and takes out fully-coated devices on the other end, ready for packaging.  Everything in the middle is in a big black box…. maybe not literally, unless you paint the coating apparatus black.

Manual Processes – Advantages

Cheaper to create – designing and implementing a dip coating process in this fashion, complete with an oven, can be done for less than $100,000.

Good for low volumes – if you are only making 10,000 or so devices per year, why spend money on something big?  A system that can crank out 100 devices per day will work fine.

Expandable – got more devices to coat in Year 2?  Add a second dipper and oven set.  Done.  No redesign necessary, unless you count fiddling with your floor layout.

Cheap labor – in places (countries) with cheap labor, you may actually save money by filling a room with workers rather than paying a high prices for a fully-automated rig.

Automated Processes – Advantages

It’s automated – no brainer.  More automation means less personal interaction with the product, which means less errors caused by human factors.

Good for high volume – if the 100/day rate doesn’t cut it for you, because you are making 100,000 devices per year or more, this is the way to go.

Design – if you are using a hi-tech piece of equipment, chances are it has a lot more thought put into its design in terms of safety and material handling, not to mention ease of use

Labor costs – In places with high labor costs, it may not pay to have many manual workers.  A setup like this could be run by a couple of people per machine.

Manual Processes – Disdvantages

Design – the cheaper price tag on designing this kind of system may mean you get what you pay for: less attention to safety and usability

Bad for high volumes – at some point, this process is not expandable because of the size of your clean room and the number of workers you must hire.  Granted, that limit can go fairly high, but you will hit it eventually if you are successful, and have to change your process.

Human Interaction – the more human interaction you have with a product, the more chance there is for something to go wrong related to that.

Expensive Labor – in countries where the labor costs are high, it may not be smart to have many people working at stations doing coatings if you have to pay them benefits, 401K, pensions, etc.

Automated Processes – Disadvantages

It’s automated – when something breaks, you have to fix it.  In the meantime,  your coating line is down.  If you have to wait days for a replacement part, guess what?

Bad for low volume – if you have read this far, you understand this now.  There’s no reason to pay $400,000 for a grand automated coating system if you are making 1,000 devices per year and selling them for $50/piece.

Design – you will constantly be working against design flaws in the coating product, especially in the beginning.  This could affect production.

Expensive – this is related to the volume disadvantage.  A startup company is not able to partake of this option.  Machines like this can cost as much as half a million dollars.