Learning how to use an Agilent 1260 LCMS (with just the diode array detector, not the MS). Oh. My. God. I last used an Agilent 1200 LC 10 years ago. This bloody 1260 is wildly complex, specifically in regard to the MassHunter data collection and workup software. It’s like a Swiss Army knife with 500 tools on it. The thing is designed for a busy analytical lab with high throughput and heavy documentation, like the boys and girls in pharma would use. I’m just using it for research. It’s like giving a taser to a monkey. It’s just a matter of time before something goes dreadfully wrong. Crimony.
I encountered this interesting article while reading about Octave Levenspiel, a prolific chemical engineer, now deceased. It is entitled Dinosaurs, but it is really about the natural history of our atmospheric composition and pressure. Have a look.
While doing some IP due diligence I ran into a patent that claimed some art of interest to me. The art was very useful, but it was claimed by a Prominent Professor of chemistry at Well Known University (WKU). Digging a bit deeper I found that the patent had expired well into it’s lifetime due to non-payment of maintenance fees. So, let’s look at this a bit deeper.
Prominent Professor files a patent application in 1998 on said art and then shoots off a paper to Well Known Publication. Then in 2003, the USPTO grants a patent to Prominent Professor and is assigned to WKU. Fine.
If the patent had been generating royalties, it seems unlikely that WKU would have allowed the patent to expire. There is no record of transfer of ownership to another assignee either. My guess is that by the time of the final maintenance fee, interest in the patent was slim to none. Seeing no royalty income likely, WKU elects to allow the patent to expire. Not uncommon.
The work produced by Prominent Professor was funded by DoE. In short, Prominent Professor received public funding and then by virtue of filing for a patent, the technology produced by said public funding is denied use by the public unless they pay again for it in a royalty agreement, unless it was under exclusive agreement with another entity. Evidently the art sat fallow for a good dozen years until it expired. Prominent Professor and WKU got a feather in their caps, and industry and the public had to sit on their thumbs during the period of unproductive time.
This is but one example of a sham allowed under public law.
I received a package from the across the Atlantic last week. It contained a small pressure transducer which, in it itself, isn’t very interesting. But what was odd was the number of layers of packaging it had. It had 6 separate bags and envelopes as well as a piece of foam.
At what point does precaution give way to fetish? They could learn something from Amazon. When in doubt, use those green air pillows and a box.
I have been an enthusiastic user of RPN calculators since high school, when Gerry Ford was president. Of course I refer to those made by Hewlett-Packard. My first was the HP-25C. The beauty of the RPN system with its 4 register stack was that it could do fairly elaborate chain calculations without the need for parentheses or an equal key. It is quite intuitive to many of us and was a pleasure to use.
But, alas! The HP RPN calculator has largely gone out of fashion it seems. Only a few models remain on the market and several are financial calculators. The HP-12C financial calculator is a wholly inadequate substitute for a scientific calculator. My 12C now sits in the desk drawer with unused pens and paper clips. All seems lost for the RPN tribe.
Or so I thought. It turns out that there is a manufacturer of Hewlett-Packard RPN clones called SwissMicros. These folks have taken the RPN baton and are running with it. Hero’s, I call them. They knew a good product when they saw it and have saved the day by manufacturing a clone that seems nearly indistinguishable from the corresponding HP unit.
I recently purchased the HP-15C clone called the DM15L. It has the look and heft of the 15C. My use thus far has been cursory, but I look forward to exploring the features. So, here is a shout out to SwissMicros!
One of the safety seminars I teach is on the general topic of reactive hazards. There is a bit of a challenge to this because the idea is to cultivate informed caution rather than allow broadband fear to rule. It is challenging because my class is generally populated with non-chemist plant operators or other support staff. Out in the world the word “chemical” is generally taken to be an epithet and indicative of some malign influence. We who work with chemicals are in a position to bear witness to the reality of chemistry in our lives and to speak calmly and reasonably about it, without crass cheerleading.
Here is how I look at this. There are hazards and there are dangers. A hazard is something that can cause harm if it was to be fully expressed by way of physical contact with people or certain objects, unbounded access to an ignition source, exposure to air, etc. A critical feature of the hazard definition is that there are layers of protection preventing undesired contact. Hazards can be contained. A contained hazard is safer to be around than an uncontained hazard.
An uncontained hazard is that which can cause harm without the interference of effective layers of protection. A hungry tiger in a cage is hazardous in that there is the potential for trouble if the cage is breached. Being openly exposed to that tiger is what I’ll call dangerous.
Likewise, a stable chemical in a bottle has a physical layer of protection around it. A policy on the use of that bottled chemical constitutes a concentric administrative layer of protection. The bottle sitting in a proper cabinet within a room with limited access has more layers of protection. The policy of selling that chemical only to qualified buyers is a further layer of protection.
Egg white to which has been added several drops of conc H2SO4 (bottom) and 50 % caustic (top). Two minutes have elapsed. The point of this demo is to show what might happed to a cornea on contact with these reagents. The clouding is irreversible. People remember demonstrations.
It is possible to work around contained hazards safely and most of us do this outside of work without giving it much thought. Hazardous energy is exploited by most of us in the form of moving automobiles, spinning jet turbines, rotating machinery of all kinds, compressed gases and springs, and flammable liquids. Safe operation around these hazards is crucial to the conduct of civilization right down to our daily lives.
It is very easy for experts to frighten the daylights out of people by an unfortunate choice of words or simply dwelling on the hazardous downside too much. Users of technology should always be versed in the good and bad elements as a matter of course.
Risk can be defined as probability times consequence. So, to reduce risk one can reduce probability, diminish undesired consequences, or both. This is the purpose of LOPA, or Layers of Protection Analysis. LOPA can provide a quantitative basis for safety policy. The video below will explain.
Designing for tolerable risk is something that all of us in industry must come to grips with.
There are many axiomatic statements to be made about the workplace. I’ll start with this:
Axiom # 1: If there is a hole, someone will fall in it.
The meaning of “hole” can vary a great deal, from a specific system weakness to an actual hole in the floor or ground. I’ve witnessed people falling into both. I think you could argue that Axiom 1 is an example of Murphy’s Law. But the ultimate origin seems to trace back to Proverbs 26:27.
My favorite corollary:
Things are never so bad that they cannot get a whole lot worse.
This sentiment was famously uttered by Humphrey Bogart in The African Queen. Countries which have been invaded by another have a special understanding of this notion.
Of course none of this is new, just crystal-clear to me this day.
The water tank heater sat submerged and frozen in place as Gramps and I crunched our way towards it in the snow. It was a circular wooden tank, grey with age and made of moss-bearded, vertical staves held in place with a rusty iron ring. It sat in the fence line, part in the barnyard and part out. The fence traced across the farmyard to a gothic red barn which sat in stony silence on the hillside. In the inky dark before sunrise a dozen angus cattle snuffled, visible shadow-like against the snow packed ground in the low moonlight.
Gramps carried a gunnysack of corn cobs and a bucket of coal. I carried a newspaper and a metal oil can sloshing with kerosene. Gramps dumped the cobs in the tank furnace, splashed some kerosene on the cobs, then covered them with coal. Taking the newspaper he rolled it into a tube, struck a match and lit one end. As the paper flared I could see his cold and weathered face. His hat with ear flaps sat low and snug over an unshaven face, his nose dripping from the cold. Gramp’s well worn overcoat was zipped tightly over his striped coveralls with pantlegs tucked inside zippered rubber overshoes. He dropped the burning paper onto the fuel mix and closed the lid.
We made our way from the tank to the barn where we dropped hay from the upper level hay mound, down the chute to ground level. The cattle, now faintly lit in the bluish morning twilight were eagerly snuffling through the parted leaves of baled hay. Making sure to gather up the twine lest the cattle eat it and sicken, we left the stillness of a barn stacked with a summer season of hay bales and made for the house.
As we crunched past the water tank, now visible under the yawning orange sky, the sooty smokestack of the tank heater belched acrid coal smoke while the light of red embers escaped through pinholes etched by the fire of 30 winters toil. Soon there would be water for the cattle to sip.
Walking a few paces behind my grandfather I looked at him in admiration. Doing chores in the frigid morning darkness seven days a weeks takes dedication. Did I have such stamina, I wondered? After 45 winters I’m still not sure.
Larry J. Westrum
8/19/18
On a recent vacation trip to the Puget Sound area I managed to take a public tour of the Boeing manufacturing facility in Everett, WA. They don’t give away the tour- it costs $25 for adults and lasts about 90 minutes. For cash you get a movie highlighting the history of Boeing and a trip to a few mezzanines overlooking the 787 Dreamliner and 747 manufacturing areas. And just like Disney, you exit the attraction tour through the gift shop.
The first thing you notice is that security is very stringent. No phones, bags or purses, etc., once the tour begins. They are an important military contractor after all. As technically savvy as they may be though, the communication level of the tour guide was roughly 6-7th grade. The reason might be the wide range of visitor ages and nationalities. One Asian visitor on our bus wore a blue track suit bearing the name “Mongolia”.
It is easy to forget just how brilliant the US is and has long been in the broader aerospace world. Of course, other countries have developed advanced aerospace platforms, and produced their share of talent too, notably France, England, Germany and Russia. But one must admit that considerable advancement has happened here for some reason. A broad industrial base with access to raw materials and capital is certainly a big part of it. Perhaps our remote location between two great oceans and historical absence of the distraction of carpet bombing by foreign adversaries has a little to do with it as well.
Balloon on a hazy day.
For many of us, aerospace brings out excitement and optimism by its very nature. It embodies much of the best in people. The pillars of aerospace are many and rely strongly on ingenuity and engineering disciplines. By discipline I mean rigorous design-then-test cycles. A human-rated flying machine is a difficult and expensive build if the goal is for people and equipment to return intact. Unlike SpaceX who has launched much cargo, and among other things, a cheese wheel and a car, NASA has been launching people for a long time. Not to diminish the fine work of SpaceX or the other commercial efforts, it’s just that NASA takes a lot of heat for their deliberate pace.
Erie Airport, Colorado, from a hot air balloon at ca 2000′.
The last week has been a period of many modes of transportation. It’s been planes, trains, automobiles, ferry boats, and a hot air balloon. The nightmare of Seattle traffic is best forgotten. If you can avoid driving in Seattle during rush hours, do so.
If you can swing a hot air balloon ride, do it. Dig up some of that cash you have buried in the back yard and spend it. I found the ride to be absent any nerve wracking moments and to be quite a serene experience. There is no wind aloft and it is dead silent when the burners aren’t going. Do bring a hat, however. The burners are bloody hot.
Getting ready for a 4-balloon launch.
Like all pilots, balloonists enjoy low level flight.
The burners emit tremendous radiant heat. A wise passenger wears a hat for this reason.
It is not uncommon to read in chemistry papers or hear speakers from academic institutions making the assertion that certain problems exist that their method or reagent may solve. Perhaps a particular catalyst may give rise to a set of useful transformations or said catalyst may be fished out and reused in many other runs. Or, maybe the reagent in development affords spectacular yields or stereoselectivity. Given that an industry might have blockbuster products that share certain features or pharmacophores, an efficient method for synthesizing that feature is likely to be of genuine interest.
Chemical research coming from an academic institution in the USA is almost always executed by students and/or postdocs. In the case of graduate students, the work is done as part of their degree program and is designed to achieve certain goals or to explore a question. Regardless, it is not done to achieve a commercial purpose with product sales in mind. Student research is conducted with training and publication success as the goal. Graduate success and publication are the work products of academics.
If it transpires that a particular academic wants to do work that is also of commercial interest, that work should include certain commercial sensibilities associated with chemical production. Every business has its own list of development criteria in use. It will have a basis on in-house equipment and skills, company policy, safety, economic imperatives, working capital, required profit margins, environmental permits, available economies of scale, specialty or commodity products, etc.
Adopting a new reagent for an existing chemical product can be very problematic for a business. For production pharmaceuticals, it is likely to be impossible for management to actually contemplate the trouble involved in changing an approved process. For other industries a similar problem exists. Changing a reagent in an existing process will likely require the customer to approve the change and the drafting of an updated specification. And, for their trouble they are going to demand a reduced price. I’ve received and given that talking to on a few occasions myself.
If the change is very early in the reaction sequence of a lined-out process, there may be a chance to do a replacement or change a step. Maybe. Remember that customers usually do not like change in regard to the chemical product they are purchasing. They want and need consistency. Even improving purity can be bad if it results in the final product surprising the end-user in some way.
I would offer that if an academic worker wants to make a difference in commerce, they should concentrate on the final product in the application. It may be that an existing product could be made cheaper by your wonder reagent, or perhaps some me-too congener. Your reagent may be superior in a functional group transformation, but that is likely to draw yawns. How does your reagent add value to a process in concrete terms?
By adding value I mean to say, increasing profit margins. Costs in manufacturing are broadly divided into raw materials, labor, cost of sales and other overhead. They are not all easy to minimize. For instance, a mature product may be priced according to commodity scale pressures. That is, there are numerous suppliers and low margins in the market for producers. If the cost of goods sold is driven strongly by raw material costs, unless you can wangle a breakthrough in raw mat prices, staying price competitive may involve a race to the bottom of the lake. However, if labor is the major driver of cost, you may have a chance to increase margins by reduction in man-hours per unit. That reduction would come from any of a number of labor saving strategies.
Labor savings can come in many forms. More efficient use of existing equipment can lead to an increase of capacity and throughput over the year if the turnaround time between runs is shortened. Process intensification can also increase throughput and consequently reduced labor hours per kg of product. Higher reaction temperatures benefit kinetics as do increased space yields by running at higher concentrations. Just beware of the reaction enthalpy per kg of reaction mass (specific enthalpy). It is very possible to over-intensify and bring on problems with safe operation and side reactions.
For the academic aiming to be technologically relevant in a concrete way you have to think like the owner of big equipment. Idle equipment is not earning revenue. Busy equipment at least has a chance if it is done efficiently. Telescoping a process so that more steps can be run in the same vessel without solvent changes or excessive purification is always desirable. Moving material between vessels is time consuming and likely labor intensive.
More questions to consider. Does a reaction really require an overnight stir-out. And at reflux? Do you have a method of in-process checks that allow the next step to proceed? What is the minimum solvent grade you can get away with? Can you replace methylene chloride with anything else? What is the minimum purity raw material you can get away with? Unnecessarily high purity specs can be very expensive. Your customer will suffer from this as well.
Learn to get pricing from bulk suppliers. Use those unit prices for your cost calculations. For God’s sake, don’t use the Aldrich catalog for pricing. Remember, you’re trying to make a case for your technology. There should be a costing spreadsheet in your write up.
That’s enough for now. I gotta go home.
Recent Comments