Brookhaven National Lab: The rapid self-assembly of nanoscale patterns for next-generation materials: From Electronics and Computing to Energy and Medicine


Brookhaven II 10-nanoparticleThe ability to quickly generate ultra-small, well-ordered nanopatterns over large areas on material surfaces is critical to the fabrication of next-generation technologies in many industries, from electronics and computing to energy and medicine. For example, patterned media, in which data are stored in periodic arrays of magnetic pillars or bars, could significantly improve the storage density of hard disk drives.

Scientists can coax thin films of self-assembling materials called block copolymers—chains of chemically distinct macromolecules (polymer “blocks”) linked together—into desired nanoscale patterns through heating (annealing) them on a substrate. However, defective structures that deviate from the regular pattern emerge early on during self-assembly.

Brookhaven6-acceleratingMaterials scientist Gregory Doerk preparing a sample for electron microscopy at Brookhaven Lab’s Center for Functional Nanomaterials. The scanning electron microscope image on the computer screen shows a cross-sectional view of line …more

The presence of these defects inhibits the use of block copolymers in the nanopatterning of technologies that require a nearly perfect ordering—such as magnetic media, computer chips, antireflective surfaces, and medical diagnostic devices. With continued annealing, the block copolymer patterns can reconfigure to remove the imperfections, but this process is exceedingly slow. The polymer blocks do not readily mix with each other, so they must overcome an extremely large energy barrier to reconfigure.

Adding small things with a big impact

Now, scientists from the Center for Functional Nanomaterials (CFN)—a U.S. Department of Energy (DOE) Office of Science User Facility at Brookhaven National Laboratory—have come up with a way to massively speed up the ordering process. They blended a line-forming block copolymer with significantly smaller polymer chains made of only one type of molecule (homopolymers) from each of the two constituent blocks. The electron microscopy images they took after annealing the films for only a few minutes show that the addition of these two smaller homopolymers dramatically increases the size of well-ordered line-pattern areas, or “grains.”

Accelerating the self-assembly of nanoscale patterns for next-generation materials
As shown in the illustration, a block copolymer consists of different molecule chains (red and blue) linked together; a homopolymer chain consists of identical molecules (red or blue). In this study, scientists blended a block copolymer …more

“Without the homopolymers, the same block copolymer cannot produce grains with these sizes,” said CFN materials scientist Gregory Doerk, who led the work, which was published online in an ACS Nano paper on December 1. “Blending in homopolymers that are less than one-tenth of the size of the block copolymer greatly accelerates the ordering process. In the resulting line patterns, there is a constant spacing between each of the lines, and the same directions of line-pattern orientations—for example, vertical or horizontal—persist over longer distances.”

Doerk and coauthor Kevin Yager, leader of the Electronic Nanomaterials Group at CFN, used image analysis software to calculate the grain size and repeat spacing of the line patterns.

While blending different concentrations of homopolymer to determine how much was needed to achieve the accelerated ordering, they discovered that the ordering sped up as more homopolymer was added. But too much homopolymer actually resulted in disordered patterns.

Accelerating the self-assembly of nanoscale patterns for next-generation materials
The scanning electron microscope images taken after thermal annealing at around 480 degrees Fahrenheit for five minutes show that the block copolymer/homopolymer blend generates a line pattern with a significantly higher degree of …more

“The homopolymers accelerate the self-assembly process because they are small enough to uniformly distribute throughout their respective polymer blocks,” said Doerk. “Their presence weakens the interface between the two blocks, lowering the energy barrier associated with the block copolymer reconfiguring to remove the defects. But if the interface is weakened too much through the addition of too much homopolymer, then the blocks will mix together, resulting in a completely disordered phase.”

Guiding the self-assembly of useful nanopatterns in minutes

To demonstrate how the rapid ordering in the blended system could accelerate the self-assembly of well-aligned nanopatterns over large areas, Doerk and Yager used line-pattern templates they had previously prepared through photolithography. Used to build almost all of today’s digital devices, photolithography involves projecting light through a mask (a plate containing the desired pattern) that is positioned over a wafer (usually made of silicon) coated with a light-sensitive material. This template can then be used to direct the self-assembly of block copolymers, which fill in the spaces between the template guides. In this case, after only two minutes of annealing, the polymer blend self-assembles into lines that are aligned across these gaps. However, after the same annealing time, the unblended block copolymer self-assembles into a mostly unaligned pattern with many defects between the gaps.

Accelerating the self-assembly of nanoscale patterns for next-generation materials
The unblended block copolymer aligns well close to the template guides (“sidewalls”), but this alignment degrades further in, as evident by the appearance of the fingerprint-like pattern in the center of the scanning electron microscope …more

“The width of the gaps is more than 80 times the repeat spacing, so the fact that we got this degree of alignment with our polymer blend is really exciting because it means we can use templates with huge gaps, created with very low-resolution lithography,” said Doerk. “Typically, expensive high-resolution lithography equipment is needed to align block copolymer patterns over this large of an area.”

For these patterns to be useful for many nanopatterning applications, they often need to be transferred to other more robust materials that can withstand harsh manufacturing processes—for example, etching, which removes layers from silicon wafer surfaces to create integrated circuits or make the surfaces antireflective. In this study, the scientists converted the nanopatterns into a metal-oxide replica. Through chemical etching, they then transferred the replica  into a silicon dioxide layer on a silicon wafer, achieving clearly defined line patterns.

Doerk suspects that blending homopolymers with other  will similarly yield accelerated assembly, and he is interested in studying blended polymers that self-assemble into more complicated patterns. The x-ray scattering capabilities at the National Synchrotron Light Source II—another DOE Office of Science User Facility at Brookhaven—could provide the structural information needed to conduct such studies.

Accelerating the self-assembly of nanoscale patterns for next-generation materials
A scanning electron microscope image showing a cross-sectional view of the line patterns transferred into a silicon dioxide layer. Credit: Brookhaven National Laboratory

“We have introduced a very simple and easily controlled way of immensely accelerating self-assembly,” concluded Doerk. “Our approach should substantially reduce the number of defects, helping to meet the demands of the semiconductor industry. At CFN, it opens up possibilities for us to use block copolymer self-assembly to make some of the new functional materials that we envision.”

 Explore further: Self-assembling polymers provide thin nanowire template

More information: Gregory S. Doerk et al. Rapid Ordering in “Wet Brush” Block Copolymer/Homopolymer Ternary Blends, ACS Nano (2017). DOI: 10.1021/acsnano.7b06154

 

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“Artificial Blood” : Part I


June 10, 2013 by tildabarliya

Artificial blood” has been the main focus of research in the past few years (1) and refers to a substance used to mimic and fulfill some functions of biological function.  Author: Tilda Barliya PhD

A number of driving forces have led to the development of artificial blood substitutes (1):

  1.  The military, which requires a large volume of blood products that can be easily stored and readily shipped to the site of casualties.
  2.  HIV; with the advent of this virus, the medical community and the public suddenly became aware of the significance of transfusion-transmitted diseases and became concerned about the safety of the national blood supply.
  3. The growing shortage of blood donors. Approximately 60% of the population is eligible to donate blood, but fewer than 5% are regular blood donors.
  4. Short shelf-life of the blood products.
  5. High hospital needs: cancer patients, transplantation etc

Artificial blood products offer many important benefits:

  • Readily available
  • Have a long shelf life
  • Can undergo filtration and pasteurization processes
  • Do not require blood typing (i.e A,B AB, O)
  • Do not appear to cause immunosuppression in the recipient.

Researchers have focused their efforts on creating artificial substitutes for 2 important functions of blood: A) oxygen transport by red blood cells and B) hemostasis by platelets (1).

A) Red Cell Substitutes:

  • Hemoglobin based
  • Perfluorocarbon (PFC) based

A1) Hemoglobin-based

The hemoglobin-based substitutes use hemoglobin from several different sources (1):

  • Human – Human hemoglobin is obtained from donated blood that has reached its expiration date and from the small amount of red cells collected as a by-product during plasma donation.
  • Animal – Animal hemoglobin is obtained from cows. This source creates some apprehension regarding the possible transmission of animal pathogens, specifically bovine spongiform encephalopathy.
  • Recombinant – Recombinant hemoglobin is obtained by inserting the gene for human hemoglobin into bacteria and then isolating the hemoglobin from the culture.

Understanding hemoglobin, its transition from a monomer to a tetramer and the way it needs to be linked to the surface of the artificial blood cells is of major issue and will be discussed in more depth in part II.

A2) Perfluorocarbon (PFC) based

PFCs are synthetic hydrocarbons with halide substitutions and are about 1/100th the size of a red blood cell. These solutions have the capacity to dissolve up to 50 times more oxygen than plasma. Because PFC solutions are modified hydrocarbons, however, they do not mix well with blood and must be emulsified with lipids or oils. The PFCs are inert products. After infusion, the molecules vaporize and are then exhaled over several days (1).

B) Platelet Substitutes:

Platelets are also at very high need due to their extremely short shelf-life (5 days) and very limited supply. Several methods have been utilized to create platelet substitutes including:

  • Infusible platelet membranes
  • Thrombospheres
  • Lyophilized human platelet product

Use and need for HLA antigen or platelet antigens, fibrinogen proteins and aggregation factors will be further discussed in part II.

In Summary:

The growing need for blood supply due to short shelf-life, limited supply and increase in disease/injured population have urged researchers to look for blood substitutes.   Although the many years of research and profound progress that have been made, there’s plenty of disadvantages having complications and  limited clinical benefits. The topic of blood substitutes will be further discussed in part II, highlighting the different substitutes that were developed, those which entered clinical trails, and the potential use of nanotechnology in this field of research.

Reference:

1. Lesley Kresie. Artificial blood: an update on current red cell and platelet substitutes. Proc (Bayl Univ Med Cent). 2001 April; 14(2): 158–161 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291332/

2. By: Tony Rairden. Synthetic Red Blood Cells Developed. http://www.nanotech-now.com/news.cgi?story_id=35993

3. By: Abdu I. Alayash. BLOOD SUBSTITUTES: Working to Fulfill a Dream. FDA voice. http://blogs.fda.gov/fdavoice/index.php/2012/06/blood-substitutes-working-to-fulfill-a-dream/

4. Jiin-Yu Chen, Michelle Scerbo, and George Kramer. A Review of Blood Substitutes: Examining The History, Clinical Trial Results, and Ethics of Hemoglobin-Based Oxygen Carriers. Clinics (San Paulo) 2009 August; 64(8): 803-813. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728196/

Nano-Tech Sealant closes wounds and hinders bacterial infection


QDOTS imagesCAKXSY1K 8A new joining material for laser welding tissue during operations has the  potential to produce stronger seals and provide an alternative to sutures and  stapling in intestinal surgery, scientists report.

Their study, which involves use of a gold-based sealing material, appears in  the journal ACS Nano.

Kaushal Rege and colleagues from Arizona State University explained in a  statement that laser tissue welding (LTW) is a stitch-free surgical method for  connecting and sealing blood vessels, cartilage in joints, the liver, the  urinary tract and other tissues.

Read more:  http://www.theengineer.co.uk/military-and-defence/news/sealant-closes-wounds-and-hinders-bacterial-infection/1016263.article#ixzz2TDXuCH98

Nanotechnology and MRI imaging


October 17, 2012 by tildabarliya

Author: Tilda Barliya PhD via Pharmaceutical Intelligence: http://pharmaceuticalintelligence.com/2012/10/17/nanotechnology-and-mri-imaging/

The recent advances of “molecular and medical imaging” as an integrated discipline in academic medical centers has set the stage for an evolutionary leap in diagnostic imaging and therapy. Molecular imaging is not a substitute for the traditional process of image formation and interpretation, but is intended to improve diagnostic accuracy and sensitivity.

Medical imaging technologies allow for the rapid diagnosis and evaluation of a wide range of pathologies. In order to increase their sensitivity and utility, many imaging technologies such as CT and MRI rely on intravenously administered contrast agents. While the current generation of contrast agents has enabled rapid diagnosis, they still suffer from many undesirable drawbacks including a lack of tissue specificity and systemic toxicity issues. Through advances made in nanotechnology and materials science, researchers are now creating a new generation of contrast agents that overcome many of these challenges, and are capable of providing more sensitive and specific information (1)

Magnetic resonance imaging (MRI) contrast enhancement for molecular imaging takes advantage of superb and tunable magnetic properties of engineered magnetic nanoparticles, while a range of surface chemistry offered by nanoparticles provides multifunctional capabilities for image-directed drug delivery. In parallel with the fast growing research in nanotechnology and nanomedicine, the continuous advance of MRI technology and the rapid expansion of MRI applications in the clinical environment further promote the research in this area.

It is well known that magnetic nanoparticles, distributed in a magnetic field, create extremely large microscopic field gradients. These microscopic field gradients cause substantial diphase and shortening of longitudinal relaxation time (T1) and transverse relaxation time (T2 and T2*) of nearby nuclei, e.g., proton in the case of most MRI applications. The magnitudes of MRI contrast enhancement over clinically approved conventional gadolinium chelate contrast agents combined with functionalities of biomarker specific targeting enable the early detection of diseases at the molecular and cellular levels with engineered magnetic nanoparticles. While the effort in developing new engineered magnetic nanoparticles and constructs with new chemistry, synthesis, and functionalization approaches continues to grow, the importance of specific material designs and proper selection of imaging methods have been increasingly recognized (2)

Earlier investigations have shown that the MRI contrast enhancement by magnetic nanoparticles is highly related to their composition, size, surface properties, and the degree of aggregation in the biological environment.

Therefore, understanding the relationships between these intrinsic parameters and relaxivities of nuclei under influence of magnetic nanoparticles can provide critical information for predicting the properties of engineered magnetic nanoparticles and enhancing their performance in the MRI based theranostic applications. On the other hand, new contrast mechanisms and imaging strategies can be applied based on the novel properties of engineered magnetic nanoparticles. The most common MRI sequences, such as the spin echo (SE) or fast spin echo (FSE) imaging and gradient echo (GRE), have been widely used for imaging of magnetic nanoparticles due to their common availabilities on commercial MRI scanners. In order to minimize the artificial effect of contrast agents and provide a promising tool to quantify the amount of imaging probe and drug delivery vehicles in specific sites, some special MRI methods, such as  have been developed recently to take maximum advantage of engineered magnetic NPs

  • off-resonance saturation (ORS) imaging
  • ultrashort echo time (UTE) imaging

Because one of the major limitations of MRI is its relative low sensitivity, the strategies of combining MRI with other highly sensitive, but less anatomically informative imaging modalities such as positron emission tomography (PET) and NIRF imaging, are extensively investigated. The complementary strengths from different imaging methods can be realized by using engineered magnetic nanoparticles via surface modifications and functionalizations. In order to combine optical or nuclear with MR for multimodal imaging, optical dyes and radio-isotope labeled tracer molecules are conjugated onto the moiety of magnetic nanoparticles

Since most functionalities assembled by magnetic nanoparticles are accomplished by the surface modifications, the chemical and physical properties of nanoparticle surface as well as surface coating materials have considerable effects on the function and ability of MRI contrast enhancement of the nanoparticle core.

The longitudinal and transverse relaxivities, Ri (i=1, 2), defined as the relaxation rate per unit concentration (e.g., millimole per liter) of magnetic ions, reflects the efficiency of contrast enhancement by the magnetic nanoparticles as MRI contrast agents. In general, the relaxivities are determined, but not limited, by three key aspects of the magnetic nanoparticles:

  1. Chemical composition,
  2. Size of the particle or construct and the degree of their aggregation
  3. Surface properties that can be manipulated by the modification and functionalization.

(It is also recognized that the shape of the nanoparticles can affect the relaxivities and contrast enhancement. However these shaped particles typically have increased sizes, which may limit their in vivo applications. Nevertheless, these novel magnetic nanomaterials are increasingly attractive and currently under investigation for their applications in MRI and image-directed drug delivery).

Composition Effect: The composition of magnetic nanoparticles can significantly affect the contrast enhancing capability of nanoparticles because it dominates the magnetic moment at the atomic level. For instance, the magnetic moments of the iron oxide nanoparticles, mostly used nanoparticulate T2 weighted MRI contrast agents, can be changed by incorporating other metal ions into the iron oxide.  The composition of magnetic nanoparticles can significantly affect the contrast enhancing capability of nanoparticles because it dominates the magnetic moment at the atomic level. For instance, the magnetic moments of the iron oxide nanoparticles, mostly used nanoparticulate T2 weighted MRI contrast agents, can be changed by incorporating other metal ions into the iron oxide.

Size Effect: The dependence of relaxation rates on the particle size has been widely studied both theoretically and experimentally. Generally the accelerated diphase, often described by the R2* in magnetically inhomogeneous environment induced by magnetic nanoparticles, is predicted into two different regimes. For the relatively small nanoparticles, proton diffusion between particles is much faster than the resonance frequency shift. This resulted in the relative independence of T2 on echo time. The values for R2 and R2*are predicted to be identical. This process is called “motional averaging regime” (MAR). It has been well demonstrated that the saturation magnetization Ms increases with the particle size. A linear relationship is predicted between Ms1/3 and d-1. Therefore, the capability of MRI signal enhancement by nanoparticles correlates directly with the particle size. 

Surface Effect: MRI contrast comes from the signal difference between water molecules residing in different environments that are under the effect of magnetic nanoparticles. Because the interactions between water and the magnetic nanoparticles occur primarily on the surface of the nanoparticles, surface properties of magnetic nanoparticles play important roles in their magnetic properties and the efficiency of MRI contrast enhancement. As most biocompatible magnetic nanoparticles developed for in vivo applications need to be stabilized and functionalized with coating materials, the coating moieties can affect the relaxation of water molecules in various forms, such as diffusion, hydration and hydrogen binding.

The early investigation carried at by Duan et al suggested that hydrophilic surface coating contributes greatly to the resulted MRI contrast effect. Their study examined the proton relaxivities of iron oxide nanocrystals coated by copolymers with different levels of hydrophilicity including: poly(maleic acid) and octadecene (PMO), poly(ethylene glycol) grated polyethylenimine (PEG-g-PEI), and hyperbranched polyethylenimine (PEI). It was found that proton relaxivities of those IONPs depend on the surface hydrophilicity and coating thickness in addition to the coordination chemistry of inner capping ligands and the particle size.

The thickness of surface coating materials also contributed to the relaxivity and contrast effect of the magnetic nanoparticles. Generally, the measured T2 relaxation time increases as molecular weight of PEG increases.

In Summary

Much progress has taken place in the theranostic applications of engineered magnetic nanoparticles, especially in MR imaging technologies and nanomaterials development. As the feasibilities of magnetic nanoparticles for molecular imaging and drug delivery have been demonstrated by a great number of studies in the past decade, MRI guiding and monitoring techniques are desired to improve the disease specific diagnosis and efficacy of therapeutics. Continuous effort and development are expected to be focused on further improvement of the sensitivity and quantifications of magnetic nanoparticles in vivo for theranostics in future.

The new design and preparation of magnetic nanoparticles need to carefully consider the parameters determining the relaxivities of the nanoconstructs. Sensitive and reliable MRI methods have to be established for the quantitative detection of magnetic nanoparticles. The new generations of magnetic nanoparticles will be made not only based on the new chemistry and biological applications, but also with combined knowledge of contrast mechanisms and MRI technologies and capabilities. As new magnetic nanoparticles are available for theranostic applications, it is anticipated that new contrast mechanism and MR imaging strategies can be developed based on the novel properties of engineered magnetic nanoparticles.

References:

1http://www.omicsonline.org/2157-7439/2157-7439-2-115.php

2http://www.clinical-mri.com/pdf/CMRI/8036XXP14Ap454-472.PDF

3http://www.thno.org/v02p0086.htm

4http://www.omicsonline.org/2157-7439/2157-7439-2-115.pdf

5http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017480/

6http://www.nature.com/nmeth/journal/v7/n12/full/nmeth1210-957.html

7http://endomagnetics.com/wp-content/uploads/2011/01/TargOncol_Review_2009.pdf

8http://www.nature.com/nnano/journal/v2/n5/abs/nnano.2007.105.html

9http://www.azonano.com/article.aspx?ArticleID=2680