Nanoparticles hold promise of preventing tumor growth

Biologists have long known cancer cells spread through the body, but not on exactly how they spread, and how to inhibit them at a molecular level. Working with an international team of cell biologists, chemists, and computational biologists, IBM Research scientist Drs. Ruhong Zhou, Seung-gu Kang and Tien Huynh, have shown in simulations that nanoparticle gadolinium metallofullerenol (Gd@C82(OH)22) prevents the spread of pancreatic cancer cells by quarantining them (see animation). It binds to and blocks the enzyme responsible for tumor metastasis and survival.
Earlier this year, the team from China led by Prof. Yuliang Zhao of the China National Center for Nanoscience and Technology discovered that the metallofullerenol could bind to breast cancer and stop its metastasis, but did not know how it happened at a molecular level. IBM's work, featured in September’s Proceedings of the National Academy of Sciences, reveals for the first time the molecular mechanism of this process. Gadolinium metallofullerenol acts as a nanomedicine via inhibition of the cancer-instigating matrix metalloproteinase enzymes (MMPs).

Finding cancer’s “off” switch

MMPs degrade the extracelluar matrix (ECM) that confines cancer cells and spurs blood vessel growth into the cancer cells. So, these enzymes not only help tumors grow and spread in the body, but also keep them healthy. Stopping this cycle was a three-fold challenge:

  1. Find the right MMP(s) (we have 27 MMPs in our bodies)
  2. Stop those MMPs’ capability to spread the tumor
  3. Stop those MMPs’ capability to feed the tumor
The China National Center for Nanoscience and Technology team's experiments show that MMP9 is the most affected of these enzymes by metallofullerenol at a cellular level. IBM's team ran molecular dynamics simulations for a few months on a Blue Gene supercomputer and found that gadolinium metallofullerenol inactivates the function of MMP9 through an exocite binding mode near its S1’ loop, which is responsible for ligand (molecular binding point) recognition.

Knowing how to block this exocite binding mode could provide a new route for future cancer drug development. Now, IBM is looking at the MMP2 enzyme (which also was also affected in experiments) for further validation of this novel molecular inhibition mechanism.

Video of Nanoparticle Gd@C82(OH)22 Attacking a Tumor Cell

Gadolinium metallofullerenol is found to inhibit pancreatic tumor growth by about 50 percent. Similarly, it shows more than 80 percent inhibition rate to metastasis of human breast cancer in previous work (Nanomedicine 8, 136-146, February 2012). These findings may provide a new route of development of specific MMP inhibitors and effective anti-cancer nanomedicine.

IBM’s collaborators will soon begin producing these nanoparticles for phase one clinical trials. While a commercial drug is still a few years away, this is the first time we’ve understood and shown how to effectively attack cancer cells with a nanoparticle.

IBM’s Computational Biology Center collaborated with the China National Center for Nanoscience and Technology in Beijing; the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Lab, in Richland, Washington; and the Department of Chemistry at Columbia University.


Waltzing with Spintronics

IBM and ETH Zurich scientists in Zurich recently published a paper in Nature Physics which revealed the first-ever direct mapping of the formation of a persistent spin helix in a semiconductor. This new understanding in spintronics not only gives scientists unprecedented control over the magnetic movements inside devices but also opens new possibilities for creating more energy efficient electronics.

IBM scientists Matthias Walser
Matthias Walser is one of the scientists that made the discovery and he answered a few questions about himself and his research.

1. How did you get interested in your field of study?

Matthias Walser: During my time at university, IBM brought MRAMs from research to the real world and I heard more about this during a lecture by IBM scientist Rolf Allenspach, who for many years has been teaching at ETH Zurich about ferromagnetism and spintronics. Although I already had some interest in semiconductors and magnetism before, this lecture finally motivated me to apply for a PhD position in this field.

2. Your paper in Nature Physics goes back to a theoretical proposal in 2003. What made you believe that this proposal could be brought to reality in a lab?

MW: I think it is important to start a PhD with a fascinating idea: For my research it was the spin field-effect-transistor (FET). The first concept for a spin-FET was proposed in 1990, and it became famous by the name of its initiators - the Datta and Das transistor. The proposal by J. Schliemann and D. Loss follows the initial device concept in many ways, but overcomes one essential hurdle: The device does not require ballistic transport or in other words, it has the potential to work at much higher temperatures – surely a crucial benefit for applications.

But back to the original question, some proposals are more likely to work in practice than others, but there is no guarantee and possibly some subtleties hidden in the small print. Exemplary, the problem of efficient electrical spin injection into semiconductors is still unsolved. Certainly it is helpful if some knowledge and understanding is already available, but it also requires the time and means to develop and experiment with new materials and techniques. 

3. If you had to narrow it down to one thing, what was the major improvement in the paper?

Figure shows the measured spatial
and temporal spread of a spin helix.
MW: To make it clear, we can not present a spin-FET, but we can nicely illustrate how the physics behind non-ballistic spin-FET - the so-called persistent spin helix - looks in a real piece of material. 

When I started my work in 2009, J. D. Koralek and American co-workers just published the first experimental evidence for the strong lifetime enhancement that was predicted by theory. Loosely speaking, our major improvement on that is, that we can also make “photographic” recordings of the spin helix in a “stroboscope-like” way, and so we can directly map the formation of this fascinating spin state.

4. How did you know what material and technique to use and what was the ah-ha moment?

MW: Despite that silicon continues to be the number one material for the semiconductor industry, new materials such as III/V semiconductors (e.g. Gallium arsenide) have made their way to the market in the form of integrated circuits, infrared light-emitting diodes, and highly efficient solar cells. 

Material growth experts, such as our collaborators at ETH Zurich, can grow very clean and perfectly crystalline layers of such III/V semiconductor materials. By the choice of materials and the growth of multi-layer systems, one can design the optical, electrical, and magnetic properties in a certain regime -- which makes them a perfect test platform for a variety of physical phenomena.

The imaging is another story. We needed a technique that could monitor the temporal and spatial evolution of the tiny magnetic moment of an ensemble of electron spins. Two polarized laser pulses in a pump and probe configuration offer this capability if they are focused on a small spot. We first had to work on such a setup. 

The moment I saw the first periods of the spin helix appearing on the measurement monitor, I knew for sure that our setup works, and that the piece of material we use met the required properties.

5. What is next for this research?

MW: Primarily we are excited to have the technique and material ready to study such a spin helix. As we have a good understanding of the material parameters, we can now optimize the material structure. For example, there is still room for extending the lifetime of the spin helix beyond 1.1 nanoseconds. It will also be interesting to study how small constrictions and higher temperatures affect the spin helix.

In nanometer-sized devices such as CMOS devices today, we are approaching the boundary where quantum mechanical phenomena become important and interesting to study. The physics of spin is quite different than the physics of electric charge, and there is much to learn and improve until spintronics logic devices become competitive.

Thanks for your time Matthias.

Gern geschehen. (My pleasure.)


Shedding light on new frontiers of solar cell semiconductors

IBM sets world record for photovoltaic energy conversion efficiency with earth-abundant materials

Editor’s note: This article is by Teodor Todorov and David Mitzi, IBM Research photovoltaic scientists.

by David Mitzi, Teodor K. Todorov, Jiang Tang, Santanu Bag, Oki Gunawan, Tayfun Gokmen, Yu Zhu, David B. Mitzi

Energy from the sun reaching the earth’s surface amounts to several thousand times our global consumption of electricity. Yet electricity from photovoltaic (PV) solar cells currently contributes significantly less than one percent of worldwide production. Of the numerous existing PV technologies, none so far have combined the virtues of being highly efficient, cheaply scalable and made with abundantly available materials.

IBM’s Materials Science team has partnered with Solar Frontier, Tokyo Ohka Kogyo (TOK) and DelSolar to develop an efficient and affordable PV cell made of abundant natural materials. So far, the tests of our Cu2ZnSn(S,Se)4 (made of readily available copper, zinc, and tin, and referred to as CZTS) thin-film devices have achieved a world-record PV solar-to-electric power conversion efficiency of 11.1 percent (10 percent better than any previous reports) for this class of semiconductors. And it can be manufactured by simple ink-based techniques such as printing or casting.

What makes CZTS better

Currently, the most widespread PV semiconductors, made of crystalline silicon, are abundant and highly efficient. They’re in panels used for everything from home electricity to the International Space Station. However, they have extremely high material purity requirements (>99.9999 percent!), and the wafers are typically cut from large solid ingots and wired in series to form PV modules – making it expensive and difficult to upscale. 

Photos of IBM's CZTS Solar Cell Device.

Other thin-film chalcogenide materials used in PV cells, such as Cu(In,Ga)(SSe)2 (CIGS) and CdTe, have been developed to a performance level close to that of silicon, with inherently more scalable processing. They are directly deposited on large-area, low-cost substrates such as glass, metal or plastic foil. While CIGS and CdTe are easy to integrate into buildings and consumer products, their compounds contain rare and expensive elements that increase cost and limit their manufacturing levels to less than 100 Gigawatts per year (worldwide continuous electricity consumption is 15 Terawatts – 150 times greater than the level of what these CIGS can produce).

Our CZTS PV cells could potentially yield up to 500 GW/year – getting closer to the Terawatt levels of renewable electricity the planet needs. 

The focus of our joint-development team remains to further increase this device efficiency and transfer the technology to environmentally-friendly, high-throughput industrial manufacturing. The hope is that within several years this new class of photovoltaic materials will begin to contribute to the wider availability of lower-cost solar electricity. 


Reporting public health cases in real time

IBM, the Center for Disease Control and Prevention, and the New York State Department of Health are piloting a project to connect public health data with electronic health records (EHR) – which currently reside across disparate systems – to make access for health care professionals instantaneous. This access and compatibility, via an clinical document architecture (CDA) template, will help those providers, as well as other city and state services quickly react to and prevent the spread of disease.

The following interview with Shannon Kelley, Director of Programs, Office of Health Information Technology and Transformation, New York State Department of Health, discusses the progress and implications of the project.

IBM Research: What's the current state of public health case reporting in New York?

Shannon Kelley, Director of Programs, Office of Health Information Technology and Transformation, NY Dept. of Health
Shannon Kelley: Currently, laboratories (in New York and elsewhere) submit test results to the Electronic Clinical Laboratory Reporting System (ECLRS) when they have reportable conditions among New York state residents. 

Communicable Disease Electronic Surveillance System (CDESS) transfers laboratory reports from ECLRS to trigger public health case investigations conducted by Local Health Departments (LHDs) in the identification, treatment, and prevention of communicable diseases. CDESS also provides LHDs the capability to forward a case to another county to investigate as appropriate and the capability to collect supplemental forms for specific diseases. Providers may mail paper reports to LHDs for those diseases that do not need laboratory confirmation (e.g. Lyme disease diagnosed by Erythema chronicum migran rash) and these are entered into CDESS.

IBM Research:
Why were you interested in pilot testing the project to create templates for public health case reports that could work with electronic health record, and what were your results?

SK: Since 2006, New York has been investing in technology, operational capacity, and collaborative governance structures and processes to support the adoption of EHR technology, and to mobilize state-wide health information exchange to improve the quality, safety, efficiency, and affordability of health care.

Our department of health’s Universal Public Health Node (UPHN) is the state's strategic initiative to transform the health information exchange for public health. The UPHN streamlines how providers interact with the many public health information systems that currently exist – to decrease reporting burdens, promote bidirectional information exchange, and advance public health priorities.

This CDA pilot opportunity with IBM and the CDC was well-aligned with our vision for health care transformation by utilizing healthcare IT (HIT) to drive clinical and public health practice improvements. 

As part of this pilot, our partner EHR vendor and Forms Manager vendor successfully created a CDA document according to the existing template requirements, which could be transported over secure lines to NYSDOH. The department was able to receive and review the CDA document – completing the correct transport between the Forms Manager and NYSDOH. 

From a public health perspective, the CDA document can be manually viewed in a viewer as an initial report from a provider. It will require more collaboration among EHR vendor, form manager vendor, and public health to integrate CDA document with public health applications.  

IBM Research: How does this have the potential to help public health officials serve their populations better?

SK: Electronic transfer of a CDA from a provider's EHR to public health offers the ability to improve timeliness of communicable disease reporting. This would let the local health departments to begin their investigation earlier; make appropriate control recommendations to the providers; and offer preventive measures to contacts.

For example, measles lab work results can take seven to 10 days to come back from a commercial laboratory; however, control measures of vaccine administration must be completed within three days of exposure. If public health officials know about a suspected case, lab results can be facilitated and received more quickly so that cases can be prevented.

IBM Research: What are the barriers to implementing this approach today?  

SK: Here’s the piloted CDA approach:

  • Use a CCD (Continuity of Care Document) – a patient summary commonly implemented in EHR systems – to extract data about an identified case from the EHR and make the information available for use in a Reporting Form.
  • Either automatically, or at a healthcare provider's instigation, activate this Reporting Form to open for a user of the EHR system. The Reporting Form will display the information delivered by the CCD and allow the EHR user to insert more information.
  • A qualified person using the EHR would have the responsibility of making the decision to report the case to the Public Health Agency.
  • By an automated method, the information from the Reporting Form would be formatted as a specific type of CDA (for the pilot, the CDA would follow the requirements for reporting a case of pertussis) and transmitted to the Public Health Agency (PHA).
 That’s how the information transfer should work, but a few barriers remain:

  • The PHA would have to gather requirements for the triggering of the Reporting Form and the data needed for reporting for each type of reportable disease (though there may be some diseases where a positive lab result is all the information that is needed).
  • PHA will have to develop a way to populate disease surveillance system databases from CDA data.
  • Cost and time involved in implementing new procedures and perhaps new technology at the EHR system and at the PHA.
  • Different EHR systems may extract different kinds of data to create the CCD (mentioned in the first bullet above about the CCD approach); this may result in different kinds of data being reported to the PHA. 
IBM Research: Where would you like to see this collaboration go moving forward? 

Going forward, we expect that NYSDOH will be closely involved in national initiatives to develop and implement standardized approaches to electronic public health reporting from EHR systems to local and state public health program areas. Consensus around common core data elements and reporting structures for communicable diseases and other public health use case is essential to realizing a more efficient public health response system.

Availability of harmonized IT standards for public health offer great promise to alleviate the administrative burdens that presently reduce the timeliness, completeness and actionability of data. Once there are standards for EHRs to build to (and incentives for the vendors to do so), we will use our health information exchange infrastructure to transition to a fully electronic reporting system that integrates data from the provider or EHR source to the NYSDOH program application.

Bidirectional data flow is also important, so the ability to generate automated acknowledgements of data received or requests for additional data is also important to reducing unnecessary outreach to providers.


Box Office to Front Office: Winning with Big Data

On Friday, August 10, 2012, the latest installment of the IBM Research Colloquia, "Box Office to Front Office: Winning with Big Data," will convene Bay Area thought leaders and experts in sports and entertainment for a discussion on using Big, Fast Data to engage consumers, develop products and drive revenue.

Join our livestream web event to hear how our esteemed panelists are using Big, Fast Data to deliver measurable growth in their markets, how global brands are shifting from understanding markets to understanding people to drive deeper engagement, and exploring how leading sports, media and entertainment companies are rethinking their data environments to create new value – using analytics and social and mobile technologies to innovate customer life cycles, create differentiated experiences and engage with key stakeholders.

An IBM Research expert will be logged in to the livestream chat to address any questions or comments. 

The event will also be hosted by IBM researcher Jeff Nichols on the People for a Smarter Planet Facebook page

Program Agenda

Overview: When people think of movies, television, video games, and sports, we rarely think about the intense amount of data involved and the intricate systems required to access, analyze and do something impactful with that data. Each panelist will touch on this in some form ranging from engaging consumers, developing content/products, on-field performance and more.

August 10 / 10:00 a.m. - 12:00 p.m. US Pacific

IBM San Francisco / Livestream

Keynote: Michael Karasick, Vice President and Lab Director, IBM Research - Almaden

Entertainment Panel
10:00 a.m.

Sports Panel
11:00 a.m.