Tag Archives: Valley of Death

Researchers, manufacturers, and administrators need to consider shared quality control challenges to advance the nanoparticle manufacturing industry ‘

Manufacturing remains a bit of an issue where nanotechnology is concerned due to the difficulties of producing nanoparticles of a consistent size and type,


Electron micrograph showing gallium arsenide nanoparticles of varying shapes and sizes. Such heterogeneity [variation]  can increase costs and limit profits when making nanoparticles into products. A new NIST study recommends that researchers, manufacturers and administrators work together to solve this, and other common problems, in nanoparticle manufacturing. Credit: A. Demotiere, E. Shevchenko/Argonne National Laboratory

The US National Institute of Standards and Technology (NIST) has produced a paper focusing on how nanoparticle manufacturing might become more effective, from an August 22, 2018 news item on ScienceDaily,

Nanoparticle manufacturing, the production of material units less than 100 nanometers in size (100,000 times smaller than a marble), is proving the adage that “good things come in small packages.” Today’s engineered nanoparticles are integral components of everything from the quantum dot nanocrystals coloring the brilliant displays of state-of-the-art televisions to the miniscule bits of silver helping bandages protect against infection. However, commercial ventures seeking to profit from these tiny building blocks face quality control issues that, if unaddressed, can reduce efficiency, increase production costs and limit commercial impact of the products that incorporate them.

To help overcome these obstacles, the National Institute of Standards and Technology (NIST) and the nonprofit World Technology Evaluation Center (WTEC) advocate that nanoparticle researchers, manufacturers and administrators “connect the dots” by considering their shared challenges broadly and tackling them collectively rather than individually. This includes transferring knowledge across disciplines, coordinating actions between organizations and sharing resources to facilitate solutions.

The recommendations are presented in a new paper in the journal ACS Applied Nano Materials.

An August 22, 2018 NIST news release, which originated the news item, describes how the authors of the ACS [American Chemical Society) Applied Nano Materials paper developed their recommendations,

“We looked at the big picture of nanoparticle manufacturing to identify problems that are common for different materials, processes and applications,” said NIST physical scientist Samuel Stavis, lead author of the paper. “Solving these problems could advance the entire enterprise.”

The new paper provides a framework to better understand these issues. It is the culmination of a study initiated by a workshop organized by NIST that focused on the fundamental challenge of reducing or mitigating heterogeneity, the inadvertent variations in nanoparticle size, shape and other characteristics that occur during their manufacture.

“Heterogeneity can have significant consequences in nanoparticle manufacturing,” said NIST chemical engineer and co-author Jeffrey Fagan.

In their paper, the authors noted that the most profitable innovations in nanoparticle manufacturing minimize heterogeneity during the early stages of the operation, reducing the need for subsequent processing. This decreases waste, simplifies characterization and improves the integration of nanoparticles into products, all of which save money.

The authors illustrated the point by comparing the production of gold nanoparticles and carbon nanotubes. For gold, they stated, the initial synthesis costs can be high, but the similarity of the nanoparticles produced requires less purification and characterization. Therefore, they can be made into a variety of products, such as sensors, at relatively low costs.

In contrast, the more heterogeneous carbon nanotubes are less expensive to synthesize but require more processing to yield those with desired properties. The added costs during manufacturing currently make nanotubes only practical for high-value applications such as digital logic devices.

“Although these nanoparticles and their end products are very different, the stakeholders in their manufacture can learn much from each other’s best practices,” said NIST materials scientist and co-author J. Alexander Liddle. “By sharing knowledge, they might be able to improve both seemingly disparate operations.”

Finding ways like this to connect the dots, the authors said, is critically important for new ventures seeking to transfer nanoparticle technologies from laboratory to market.

“Nanoparticle manufacturing can become so costly that funding expires before the end product can be commercialized,” said WTEC nanotechnology consultant and co-author Michael Stopa. “In our paper, we outlined several opportunities for improving the odds that new ventures will survive their journeys through this technology transfer ‘valley of death.’”

Finally, the authors considered how manufacturing challenges and innovations are affecting the ever-growing number of applications for nanoparticles, including those in the areas of electronics, energy, health care and materials.

Here’s a link to and a citation for the paper,

Nanoparticle Manufacturing – Heterogeneity through Processes to Products by Samuel M. Stavis, Jeffrey A. Fagan, Michael Stopa, and J. Alexander Liddle. ACS Appl. Nano Mater., Article ASAP DOI: 10.1021/acsanm.8b01239 Publication Date (Web): August 16, 2018

Copyright © 2018 American Chemical Society

This paper is behind a paywall.

I looked at this paper briefly and found it to give a good overview. The focus is on manufacturing and making money. I imagine any discussion about the life cycle of the materials and possible environmental and health risks would have been considered ‘scope creep’.

I have two postings that provide additional information about manufacturing concerns, my February 10, 2014 posting:  ‘Valley of Death’, ‘Manufacturing Middle’, and other concerns in new government report about the future of nanomanufacturing in the US and my September 5, 2016 posting: An examination of nanomanufacturing and nanofabrication.

‘Valley of Death’, ‘Manufacturing Middle’, and other concerns in new government report about the future of nanomanufacturing in the US

A Feb. 8, 2014 news item on Nanowerk features a US Government Accountability Office (GAO) publication announcement (Note:  A link has been removed),

In a new report on nanotechnology manufacturing (or nanomanufacturing) released yesterday (“Nanomanufacturing: Emergence and Implications for U.S. Competitiveness, the Environment, and Human Health”; pdf), the U.S. Government Accountability Office finds flaws in America’s approach to many things nano.

At a July 2013 forum, participants from industry, government, and academia discussed the future of nanomanufacturing; investments in nanotechnology R&D and challenges to U.S. competitiveness; ways to enhance U.S. competitiveness; and EHS concerns.

A summary and a PDF version of the report, published Jan. 31, 2014, can be found here on the GAO’s GAO-14-181SP (report’s document number) webpage.  From the summary,

The forum’s participants described nanomanufacturing as a future megatrend that will potentially match or surpass the digital revolution’s effect on society and the economy. They anticipated further scientific breakthroughs that will fuel new engineering developments; continued movement into the manufacturing sector; and more intense international competition.

Although limited data on international investments made comparisons difficult, participants viewed the U.S. as likely leading in nanotechnology research and development (R&D) today. At the same time, they identified several challenges to U.S. competitiveness in nanomanufacturing, such as inadequate U.S. participation and leadership in international standard setting; the lack of a national vision for a U.S. nanomanufacturing capability; some competitor nations’ aggressive actions and potential investments; and funding or investment gaps in the United States (illustrated in the figure, below), which may hamper U.S. innovators’ attempts to transition nanotechnology from R&D to full-scale manufacturing.

[downloaded from http://www.gao.gov/products/GAO-14-181SP]

[downloaded from http://www.gao.gov/products/GAO-14-181SP]

I read through (skimmed) this 125pp (PDF version;  119 pp. print version) report and allthough it’s not obvious in the portion I’ve excerpted from the summary or in the following sections, the participants did seem to feel that the US national nanotechnology effort was in relatively good shape overall but with some shortcomings that may become significant in the near future.

First, government investment illustrates the importance the US has placed on its nanotechnology efforts (excerpted from p. 11 PDF; p. 5 print),

Focusing on U.S. public investment since 2001, the overall growth in the funding of nanotechnology has been substantial, as indicated by the funding of the federal interagency National Nanotechnology Initiative (NNI), with a cumulative investment of about $18 billion for fiscal years 2001 through 20133. Adding the request for fiscal year 2014 brings the total to almost $20 billion. However, the amounts budgeted in recent years have not shown an increasing trend.

Next, the participants in the July 2013 forum focused on four innovations in four different industry sectors as a means of describing the overall situation (excerpted from p. 16 PDF; p. 10 print):

Semiconductors (Electronics and semiconductors)

Battery-powered vehicles (Energy and power)

Nano-based concrete (Materials and chemical industries)

Nanotherapeutics (Pharmaceuticals, biomedical, and biotechnology)

There was some talk about nanotechnology as a potentially disruptive technology,

Nanomanufacturing could eventually bring disruptive innovation and the creation of new jobs—at least for the nations that are able to compete globally. According to the model suggested by Christensen (2012a; 2012b), which was cited by a forum participant, the widespread disruption of existing industries (and their supply chains) can occur together with the generation of broader markets, which can lead to net job creation, primarily for nations that bring the disruptive technology to market. The Ford automobile plant (with its dramatic changes in the efficient assembly of vehicles) again provides an historical example: mass – produced automobiles made cheaply enough—through economies of scale—were sold to vast numbers of consumers, replacing horse and buggy transportation and creating jobs to (1) manufacture large numbers of cars and develop the supply chain; (2) retail new cars; and (3) service them. The introduction of minicomputers and then personal computers in the 1980s and 1990s provides another historical example; the smaller computers disrupted the dominant mainframe computing industry (Christensen et al. 2000). Personal computers were provided to millions of homes, and an analyst in the Bureau of Labor Statistics (Freeman 1996) documented the creation of jobs in related areas such as selling home computers and software. According to Christensen (2012b), “[A]lmost all net growth in jobs in America has been created by companies that were empowering—companies that made complicated things affordable and accessible so that more people could own them and use them.”14 As a counterpoint, a recent report analyzing manufacturing today (Manyika et al. 2012, 4) claims that manufacturing “cannot be expected to create mass employment in advanced economies on the scale that it did decades ago.”

Interestingly, there is no mention in any part of the report of the darker sides of a disruptive technology. After all, there were people who were very, very upset over the advent of computers. For example, a student (I was teaching a course on marketing communication) once informed me that she and her colleagues used to regularly clear bullets from the computerized equipment they were sending up to the camps (memory fails as to whether these were mining or logging camps) in northern British Columbia in the early days of the industry’s computerization.

Getting back to the report, I wasn’t expecting to see that one of the perceived problems is the US failure to participate in setting standards (excerpted from p. 23 PDF; p. 17 print),

Lack of sufficient U.S. participation in setting standards for nanotechnology or nanomanufacturing. Some participants discussed a possible need for a stronger role for the United States in setting commercial standards for nanomanufactured goods (including defining basic terminology in order to sell products in global markets).17

The participants discussed the ‘Valley of Death’ and the ‘Missing Middle’ (excerpted from pp. 31-2 PDF; pp. 25-6 print)

Forum participants said that middle-stage funding, investment, and support gaps occur for not only technology innovation but also manufacturing innovation. They described the Valley of Death (that is, the potential lack of funding or investment that may characterize the middle stages in the development of a technology or new product) and the Missing Middle (that is, a similar lack of adequate support for the middle stages of developing a manufacturing process or approach), as explained below.

The Valley of Death refers to a gap in funding or investment that can occur after research on a new technology and its initial development—for example, when the technology moves beyond tests in a controlled laboratory setting.22 In the medical area, participants said the problem of inadequate funding /investment may be exacerbated by requirements for clinical trials. To illustrate, one participant said that $10 million to $20 million is needed to bring a new medical treatment into clinical trials, but “support from [a major pharmaceutical company] typically is not forthcoming until Phase II clinical trials,” resulting in a  Valley of Death for  some U.S. medical innovations. Another participant mentioned an instance where a costly trial was required for an apparently low risk medical device—and this participant tied high costs of this type to potential difficulties that medical innovators might have obtaining venture capital. A funding /investment gap at this stage can prevent further development of a technology.

The term  Missing Middle has been used to refer to the lack of funding/investment that can occur with respect to manufacturing innovation—that is, maturing manufacturing capabilities and processes to produce technologies at scale, as illustrated in figure 8.23 Here, another important lack of support may be the absence of what one participant called an “industrial commons”  to sustain innovation within a  manufacturing sector.24 Logically, successful transitioning across the  middle stages of manufacturing development is a prerequisite to  achieving successful new approaches to manufacturing at scale.

There was discussion of the international scene with regard to the ‘Valley of Death’ and the ‘Missing Middle’ (excerpted from pp. 41-2 PDF; pp. 35-6 print)

Participants said that the Valley of Death and Missing Middle funding and investment gaps, which are of concern in the United States, do not apply to the same extent in some other countries—for example, China and Russia—or are being addressed. One participant said that other countries in which these gaps have occurred “have zeroed in [on them] with a laser beam.” Another participant summed up his view of the situation with the statement: “Government investments in establishing technology platforms, technology transfer, and commercialization are higher in other countries than in the United States.”  He further stated that those making higher investments include China, Russia, and the European Union.

Multiple participants referred to the European Commission’s upcoming Horizon 2020 program, which will have major funding extending over 7 years. In addition to providing major funding for fundamental research, the Horizon 2020 website states that the program will help to:

“…bridge the gap between research and the market by, for example, helping innovative enterprises to develop their technological breakthroughs into viable products with real commercial potential. This market-driven approach will include creating partnerships with the private sector and Member States to bring together the resources needed.”

A key program within Horizon 2020 consists of the European Institute of Innovation and Technology (EIT), which as illustrated in the “Knowledge Triangle” shown figure 11, below, emphasizes the nexus of business, research, and higher education. The 2014-2020 budget for this portion of Horizon 2020 is 2.7 billion euros (or close to $3.7 billion in U.S. dollars as of January 2014).

As is often the case with technology and science, participants mentioned intellectual property (IP) (excerpted from pp. 43-44 PDF; pp. 37-8 print),

Several participants discussed threats to IP associated with global competition.43 One participant described persistent attempts by other countries (or by certain elements in other countries) to breach information  systems at his nanomanufacturing company. Another described an IP challenge pertaining to research at U.S. universities, as follows:

•due to a culture of openness, especially among students, ideas and research are “leaking out” of universities prior to the initial researchers having patented or fully pursued them;

•there are many foreign students at U.S. universities; and

•there is a current lack of awareness about “leakage” and of university policies or training to counter it.

Additionally, one of our earlier interviewees said that one country targeted. Specific research projects at U.S. universities—and then required its own citizen-students to apply for admission to each targeted U.S. university and seek work on the targeted project.

Taken together with other factors, this situation can result in an overall failure to protect IP and undermine U.S. research competitiveness. (Although a culture of openness and the presence of foreign students are  generally considered strengths of the U.S. system, in this context such factors could represent a challenge to capturing the full value of U.S. investments.)

I would have liked to have seen a more critical response to the discussion about IP issues given the well-documented concerns regarding IP and its depressing affect on competitiveness as per my June 28, 2012 posting titled: Billions lost to patent trolls; US White House asks for comments on intellectual property (IP) enforcement; and more on IP, my  Oct. 10, 2012 posting titled: UN’s International Telecommunications Union holds patent summit in Geneva on Oct. 10, 2012, and my Oct. 31, 2011 posting titled: Patents as weapons and obstacles, amongst many, many others here.

This is a very readable report and it answered a few questions for me about the state of nanomanufacturing.

ETA Feb. 10, 2014 at 2:45 pm PDT, The Economist magazine has a Feb. 7, 2014 online article about this new report from the US.

ETA April 2, 2014: There’s an April 1, 2014 posting about this report  on the Foresight Institute blog titled, US government report highlights flaws in US nanotechnology effort.

Over 2000 nanotechnology businesses?

Nanowerk has announced a new, free feature: their Nanotechnology Company Directory. From the July 1, 2010 news item,

At the latest count, over 2100 companies from 48 countries are involved in nanotechnology research, manufacturing or applications – a number that keeps growing at a considerable pace.

With more than 1100 companies, the U.S. is home to roughly half of all nanotechnology firms. 670 companies are in Europe, 230 in Asia and 210 elsewhere in the world. Within Europe, Germany is represented with 211 companies, followed by the U.K. with 146 companies.

Over 270 companies are involved in the manufacture of raw materials such as nanoparticles, nanofibers and -wires, carbon nanotubes, or quantum dots. More than 340 companies are active in life sciences and pharmaceutical fields. The vast majority with well over half of all companies are involved in manufacturing instruments, devices, or advanced materials and components.

The news item goes on to provide a definition for what constitutes a nanotechnology company which is timely in light of Dexter Johnson’s June 30, 2010 posting (What Is a Nanotechnology Company Anyway?) at Nanoclast,

I stopped for a moment after reading [in an investment notice he’d received] this term “nanotechnology company” to consider what might actually constitute such a thing. Is Toyota a nanotechnology company as some nanotechnology stock indices have claimed? Is IBM a nanotechnology company because they are doing research into using graphene and carbon nanotubes in electronics? How about all the instrumentation and microscopy companies that give us the tools to see and to work on the nanometer and angstrom scale, are they nanotechnology companies? What about the flood of nanomaterials companies that started making carbon nanotubes in their basements that were going to revolutionize industry?

Despite figures ranging from one to three trillion dollars being dangled in front of people’s faces for the last 10 years, it doesn’t seem to have attracted the level of investment that would really make a difference in advancing the commercial aspirations of nanotechnologies if the recent PCAST meeting is any indication.

So the definition has an impact since entrepreneurs need to attract investment and, as  more than one of the participants in the recent PCAST meeting noted, moving the discoveries from the laboratory to the market place is a labourious process where there is a significant dearth of investment interest for a phase described as the ‘valley of death’ or, as one participant termed it, the ‘lab gap’. (My post about that particular PCAST meeting ‘The Golden Triangle workshop’  is here.)

The same day Nanowerk announced its new nanotechnology company directory, Christine Peterson at the Foresight Institute posted an item about a venture capital group known for investing in nanotech and microsystems,

Small investors who want to invest in nanotech startups have for years turned to publicly-held venture group Harris & Harris Group, which has focused on private companies in nanotech and microsystems.

With the economy down, and initial public offerings (IPOs) more rare, this strategy is changing.

Peterson is commenting on a Wall Street Journal blog posting by Brian Gormley,

In a June 28 letter to shareholders, Chief Executive [of Harris & Harris Group] Douglas Jamison said many of its private holdings are maturely nicely. Even so, volatility and risk aversion in the public markets are making it difficult for these companies [nanotech and microsystems] to go public.

Although the firm plans to continue investing in private companies, “We currently do not plan to make an initial equity investment in a private company until we get increased visibility into the timing of liquidity for our privately held portfolio,” Jamison wrote in the letter.

The firm, which has 31 private investments in its portfolio, expects to gain such visibility later this year. Jamison was not available for comment Monday.

“With the lengthening time between investment and return on investment in private venture capital-backed companies, we need to find a way to generate returns with greater frequency,” Jamison said in the letter.

“As a public company, we should not count on investors to wait five years between liquidity events. We will seek to position our investments so that we can demonstrate positive returns on investments on an annual basis.”

The valley of death or lab gap seems to be getting wider while venture capitalists who do know the industry pull back. Meanwhile, a standard investor is likely to experience confusion about what the term nanotechnology company means and just how much that ‘market’ is liable to worth.

The memristor rises; commercialization and academic research in the US; carbon nanotubes could be made safer than we thought

In 2008, two memristor papers were published in Nature and Nature Nanotechnology, respectively. In the first (Nature, May 2008 [article still behind a paywall], a team at HP Labs claimed they had proved the existence of memristors (a fourth member of electrical engineering’s ‘Holy Trinity of the capacitor, resistor, and inductor’). In the second paper (Nature Nanotechnology, July 2008 [article still behind a paywall]) the team reported that they had achieved engineering control.

I mention this because (a) there’s some new excitement about memristors and (b) I love the story (you can read my summary of the 2008 story here on the Nanotech Mysteries wiki).

Unbeknownst to me in 2008, there was another team, located in Japan, whose work  on slime mould inspired research by a group at the University of California San Diego (UC San Diego)  which confirmed theorist Leon Chua’s (he first suggested memristors existed in 1971) intuition that biological organisms used memristive systems to learn. From an article (Synapse on a Chip) by Surf daddy Orca on the HPlus magazine site,

Experiments with slime molds in 2008 by Tetsu Saisuga at Hokkaido University in Sapporo sparked additional research at the University of California, San Diego by Max Di Ventra. Di Ventra was familiar with Chua’s work and built a memristive circuit that was able to learn and predict future signals. This ability turns out to be similar to the electrical activity involved in the ebb and flow of potassium and sodium ions across cellular membranes: synapses altering their response according to the frequency and strength of signals. New Scientist reports that Di Ventra’s work confirmed Chua’s suspicions that “synapses were memristors.” “The ion channel was the missing circuit element I was looking for,” says Chua, “and it already existed in nature.”

Fast forward to 2010 and a team at the University of Michigan led by Dr. Wei Lu showing how synapses behave like memristors (published in Nano Letters, DOI: 10.1021/nl904092h [article behind paywall]). (Fromthe  HPlus site article)

Scientific American describes a US military-funded project that is trying to use the memristor “to make neural computing a reality.” DARPA’s Systems of Neuromorphic Adaptive Plastic Scalable Electronics Program (SyNAPSE) is funded to create “electronic neuromorphic machine technology that is scalable to biological levels.”

I’m not sure if the research in Michigan and elsewhere is being funded by DARPA (the US Dept. of Defense’s Defense Advanced Research Project Agency) although it seems likely.

In the short term, scientists talk about energy savings (no need to reboot your computer when you turn it back on). In the longer term, they talk about hardware being able to learn. (Thanks to the Foresight Institute for the latest update on the memristor story and the pointer to HPlus.) Do visit the HPlus site as there are some videos of scientists talking about memristors and additional information (there’s yet another team working on research that is tangentially related).

Commercializing academic research in US

Thanks to Dave Bruggeman at the Pasco Phronesis blog who’s posted some information about a White House Request for Information (RFI) on commercializing academic research. This is of particular interest not just because of the discussion about innovation in Canada but also because the US National Nanotechnology Initiative’s report to PCAST (President’s Council of Advisors on Science and Technology, my comments about the webcast of the proceedings here). From the Pasco Phronesis posting about the NNI report,

While the report notes that the U.S. continues to have a strong nanotechnology sector and corresponding support from the government. However, as with most other economic and research sectors, the rest of the world is catching up, or spending enough to try and catch up to the United States.

According to the report, more attention needs to be paid to commercialization efforts (a concern not unique to nanotechnology).

I don’t know how long the White House’s RFI has been under development but it was made public at the end of March 2010 just weeks after the latest series of reports to PCAST. As for the RFI itself, from the Pasco Phronesis posting about it,

The RFI questions are organized around two basic concerns:

  • Seeking ideas for supporting the commercialization and diffusion of university research. This would include best practices, useful models, metrics (with evidence of their success), and suggested changes in federal policy and/or research funding. In addition, the RFI is interested in how commercialization ecosystems can be developed where none exist.
  • Collecting data on private proof of concept centers (POCCs). These entities seek to help get research over the so-called “Valley of Death” between demonstrable research idea and final commercial product. The RFI is looking for similar kinds of information as for commercialization in general: best practices, metrics, underlying conditions that facilitate such centers.

I find the news of this RFI a little surprising since I had the impression that commercialization of academic research in the US is far more advanced than it is here in Canada. Mind you, that impression is based on a conversation I had with a researcher a year ago who commented that his mentor at a US university rolled out more than 1 start up company every year. As I understand it researchers in Canada may start up one or two companies in their career but never a series of them.

Carbon nanotubes, is exposure ok?

There’s some new research which suggests that carbon nanotubes can be broken down by an enzyme. From the news item on Nanowerk,

A team of Swedish and American scientists has shown for the first time that carbon nanotubes can be broken down by an enzyme – myeloperoxidase (MPO) – found in white blood cells. Their discoveries are presented in Nature Nanotechnology (“Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation”) and contradict what was previously believed, that carbon nanotubes are not broken down in the body or in nature. The scientists hope that this new understanding of how MPO converts carbon nanotubes into water and carbon dioxide can be of significance to medicine.

“Previous studies have shown that carbon nanotubes could be used for introducing drugs or other substances into human cells,” says Bengt Fadeel, associate professor at the Swedish medical university Karolinska Institutet. “The problem has been not knowing how to control the breakdown of the nanotubes, which can caused unwanted toxicity and tissue damage. Our study now shows how they can be broken down biologically into harmless components.”

I believe they tested single-walled carbon nanotubes (CNTs) only as the person who wrote the news release seems unaware that mutil-walled CNTs also exist. In any event, this could be very exciting if this research holds up under more testing.