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More Effectively Targeting Cancer Preferen&ally  destroy  malignant   cancer   DNA   and   not   healthy   cells  and  &ssue   CAMD  x-­‐rays  are  more  effec&ve   than  conven&onal  hospital   therapy   Auger Electron Therapy IUdR  molecules  bind  to  cancer  DNA  and  CAMD  x-­‐rays  are  tuned   to  specifically  excite  the  iodine  atoms  they  contain   The  iodine  releases  Auger  electrons  effecAvely  killing  the  cancer   cells  and  not  harming  healthy  Assue     This  therapy  being  developed  at  CAMD  is  a  collabora8on  of  the     LSU  Medical  Physics  Group  and  the  Mary  Bird  Perkins  Cancer  Center  

Ken  Hogstrom,  Kip  MaBhews,  Physics  and  Astronomy  


Protein Crystallography Assemble   proteins   into   crystalline   arrays   to   determine   structures  –    measure  the  paBerns  that  x-­‐rays  scaBer  into  

a  protein  crystal  is  a  uniform   array  of  individual  proteins  

the  data  is  a  collec&on  of   scaBered  spots  /  intensi&es   (use  mad  phasing)  

the  result  is  a  precise  determina&on   of  where  the  atoms  are  within  each   protein  molecule  

Used for Drug Discovery and to Understand Disease The  response  of  cells  to  drugs  and  the  origin  of  disease  rely  on   iden&fica&on  of  binding  sites  in  cells  for  therapy  and  interven&on.   The  NIH  supports  a  consor8um  of  8  universi8es  and  medical  schools   to  conduct  protein  crystallography  at  CAMD  

Yong-­‐Hwan  Lee,  Marcia  Newcomer,  Grover  Waldrop   Biological  Sciences  


Starving  

Cancer

Cancer  cells  feed  differently  and  the   protein  PFKFB3  is  implicated  as  the  cause   Devise  an  inhibitor  to  bind  to  PFKFB3  and  block  its  acAvity  – prevent  cancer  cells  from  generaAng  energy  –  starve  them  

Structure  of  PFKFB3  

Poten&al  Inhibitor  

CAMD measures structure via Protein Crystallography

+  

Ligand

       PFKFB3                      Inhibitor                    Disabled  Protein                                                        

Structural  determina8on  and  screening  to  see  which  poten8al   inhibitors  bind  allow  one  to  discover  new  an8-­‐cancer  drugs   applica8ons   in   cancer   therapy,   glucose   regula8on,  rescue  heart  from  ischemic  damage  …  

Yong-­‐Hwan  Lee,  Biological  Sciences  


Triggers of Inflammatory Response Biosynthesis  of  leukotrienes  trigger  immune  responses  like   asthma  and  have  links  to  disease  like  atherosclerosis  

Analysis  of  diffrac&on  paBern  provides  structure  of   the  enzyme  ini&a&ng  inflammatory  responses   PX  diffrac&on   paBern  is  spots   of  scaBered  x-­‐ rays  of  different   intensi&es  

enzyme  lipoxygenase     Use CAMD to measure protein structures •  U-­‐shaped  channel  in  the  enzyme  is   consistent  with  chemical  ac8vity   •  work  in  progress  to  find  molecules   that  bind  to  this  site  and  block  its   ac8vity    

Marcia  Newcomer,  Biological  Sciences  


RESISTING

RESISTANCE CAMD LEADS THE FIGHT AGAINST ANTIBIOTIC RESISTANT BACTERIA USING STRUCTURE - BASED DRUG DESIGN

PROTEIN STRUCTURE SOLVED AT CAMD

CAMD

ADB

Grover  Waldrop,  Biological  Sciences  


NANO  par&cles for  Cancer  Diagnosis  and  Treatment MagneAc  nanoparAcles  can  be  funcAonalized  with  hormones  such  as   LHRH  that  preferenAally  locate  within  malignant  cells  

Magnetic particles can be used for cancer detection Surface-functionalized particles can deliver drugs LHRH-­‐treated  nanopar.cles   preferen.ally  cluster  within  malignant   cells,  untreated  nanopar.cles  do  not  

Fe3O4

synthesis  of   nanopar.cles  in     CAMD  microreactor  

LHRH-­‐funcAonalized  Fe3O4  parAcles  accumulate  in  primary   tumors  and  metastaAc  cells  while  uncoated  accumulate  in  liver   Carola  Leuschner,  Pennington  Biomedical  Research  Center   Challa  Kumar,  CAMD  

(start-­‐up  company)  


$12.5M     Research   Center  

Utrecht     University,   NL  

Jerry  Spivey,  Challa  Kumar,  Kerry  Dooley,  John  Flake,  Greg  Griffin,     Richard  Kurtz,  Ward  Plummer,  Phillip  Sprunger   Chemical  Engineering,  Physics  and  Astronomy   CAMD  


Magne&c Refrigera&on

Arc-­‐Melt  Synthesis                      Pulsed-­‐Laser  DeposiAon  

Refrigerate  by  moving  sample  into  and  out  of  a  magne&c  field  

1  

Simple  (in  principle):  

2  

1.  2.  3.  4.  5. 

3  

4  

5  

magneAc  moments  disordered,  magnet  at  ambient  temperature   a  magneAc  field  aligns  sample’s  magneAc  moments   alignment  causes  sample  to  release  heat  to  ambient   sample  cools  to  ambient  temperature  in  the  field   remove  from  magneAc  field,  moments  disorder  and  sample  absorbs   heat  from  environment  

solid  state  refrigera&on  ~60%  efficient   BEST  gaseous  refrigera&on  ~  40%  efficient  

Shane  Stadler,  Eizi  Morikawa,  Pingheng  Zhou   Physics  and  Astronomy  and  CAMD  


Alternative Fuels From Biomass Gasifica&on’s  primary  concern  is  contaminated  feed  stock   Minimum  Conversion  Processing   Cost  of   Ethanol  Produc&on,  $/gal   (2007$s)

$1.40  

Feed  Handling  and  Drying Gasifica&on Syngas  Cleanup  &  Condi&oning Fuels  Synthesis Product  Recovery  and  Purifica&on Balance  of  Plant

$1.20   $1.00   $0.80   $0.60   $0.40   $0.20   $0.00  

$(0.20)

$1.21/gal 2005 State  of  Technology

$1.11/gal 2009  Target

$0.65/gal 2012  Target

Sulfur  is  the  primary  culprit  that  must  be  removed   Use CAMD to measure catalyst performance and stability Center for Atomic-Level Catalyst Design DOE Energy Frontier Research Center

Catalyst  efficiency  and  lifeAme  are  criAcal  to  finding     green  methods  of  energy  generaAon.   The  Department  of  Energy  has  funded  LSU  and  CAMD  with  an   Energy  Fron8er  Research  Center   Kerry  Dooley,  Chemical  Engineering  


Nanoscience Use  Sunlight  to  Produce  Hydrogen H2-­‐Powered  HONDA  FCX  Clarity   Zero  emissions  (only  water!)  

Fuel  Tank  is  3.92  kg  of  H2    –  Range  is  240  mi  

TiO2  –  a  ingredient  in  toothpaste,   paint,  paper  –  makes  them  white    

splits  water  but  it  is  inefficient  

100  nm2  

use   silver   nanoclusters   on   TiO2   act   as   antennas   to  absorb  sunlight  more   efficiently  –  plasmons!  

If  you  had  a  30  m2  panel  on  the  roof  of  your  garage    15%  efficient   you  could  generate  a  “tank”  of  hydrogen  every  5.5  days     (almost)  FREE  GAS!   Use CAMD to measure nanocluster performance CAMD  allows  us  to  directly  monitor  the  spliQng  of   water  molecules  with  photoelectron  spectroscopy   We   are   currently   working   on   enhancing   performance  and  stability  in  an  electrolyte   Richard  Kurtz,  Phillip  Sprunger,  Physics  and  Astronomy  


Nanoscience Nanowires  are  not  normal  metals Angle dependence ALONG Angle dependence PERP

50  Å  

Ag-d bands

Ag-d bands 5

hν=16 eV  

Cu substrate

4

4

3

3

_   2 X  

2

_   Y  

1

1

       1000  Å  

Cu substrate

Γ   0

0 -6

-4

-2

Binding Energy (eV)

0

Γ   -6

-4

-2

0

Binding Energy (eV)

Electrons  are  ejected  from  the  nanowires  with  synchrotron  light   The  wires  are  insulaAng  across  the  wire  but  conducAng  along!       Quantum Mechanics rules on the nanoscale This  may  have  implica8ons  for  semiconductor  interconnec8ons  when   linewidths  get  to  the  nanoscale  –  crossed  wires  may  not  conduct  normally   These  wires  are  quasi  1-­‐dimensional  conductors   Phillip  Sprunger,  Richard  Kurtz,  Physics  and  Astronomy  


Synthesizing

NANO  par&cles

Cobalt  nanoparAcles  are  produced  in  a  chemical  reacAon  of  two   reagents  in  a  microfluidic  flow  reactor  produced  at  CAMD.  

Monitor the reaction completion at different points to establish conditions producing preferred product X-­‐rays  monitor  product  at   various  loca.ons  during  the   chemical  reac.on  

Once  synthesized,  the  surfaces  of  the  nanoparAcles  can  be   funcAonalized  with  bio-­‐compaAble  molecules  for  drug  delivery   Microfluidic  approach  to  cluster  synthesis  provides  the  opportunity  to   control  reac8on  kine8cs  and  thereby  the  nature  of  the  nanopar8cle  product  

Challa  Kumar,  CAMD  


Environmental Toxicology During   combus&on,   nanopar&cles   form   on   soot   and   catalyze  the  produc&on  of  toxic  chemicals  like  dioxin  

CAMD identifies the culprit to guide prevention of these oxides

These  nano-­‐oxides  are  highly  effec&ve  at  producing  toxins  that  can   transfer  from  the  lungs  to  the  heart  causing  widespread  damage.   A  SUPERFUND  CENTER  has  been  established  at  LSU  by  the  NIEHS  –   Na8onal  Ins8tute  of  Environmental  Health  Sciences  –  to  study  this  problem  

Barry  Dellinger,  Erwin  Poliakoff,  Randy  Hall,  Slawomir   Lomniki,  Margaret  Reams,  Maud  Walsh,  Isiah  Warner  


HEAVY  METAL

Zn

Toxic  Metal  Transport  and  Adsorp&on  in  Soil Natural  organic  ligands  influence  the  transport  and  adsorpAon  of  heavy   metals  in  soils.    Studies  of  low  molecular  weight  ligands  may  provide   insight  into  and  beier  understanding  of  the  adsorpAon  processes.  

The  complexity  of  the  humic  acid  structure,  a  high  molecular  weight   ligand,  makes  it  difficult  to  model  the  complexaAon  and  adsorpAon   processes  that  occur. Extended  X-­‐ray  Absorp.on  Fine   Structure  (EXAFS)  at  CAMD  reveals  the   bonding  of  organic  ligands  to  Zn  

Heavy  metals  like  zinc  adsorb  onto  oxides  of  iron  and  aluminum   but  organic  material  in  soil  affects  the  binding  of  zinc  

Jim  Wang   School  of  Plant,  Environmental,  and  Soil  Sciences   LSU  AgCenter  


Metalloids and Biofilms

As

Linking  Microbial  Diversity  to  As  Mobility   El  TaAo  Geyser  Field,  Chile   XANES  at  CAMD  is  used  for  speciaAon  –  to  idenAfy  the  elemental   compounds  that  form  and  the  valence  states  of  metals

AnneBe  Summers  Engel   Department  of  Geology  and  Geophysics  


Microfabrication Enabling  Capabili&es X-­‐Ray  Mask  Technology  

Professional  Equipment  

Electroplating

Hot Embossing

MEMS Clean Room

Rigid Rigid Graphite

Graphite Material Testing Metrology

Vitreous Carbon Beryllium

Si3N4-Membrane

Alignment Window

Jost  GoeBert,  Director,  Microfabrica&on  

Lapping/Post Processing


Microfabrication Mezzo  –  A  Startup  Company Heat  Exchanger/Cooling  Applica&ons   Key  Feature:  Large  Surface  to  Volume  Ra&o  Structures   Nickel  Cryo-­‐Cooler  

Nickel  Regenerator  

25mm  

Porous  disks     COMS-­‐2006   ‘self-­‐assembled’     15µm   to  build  device   Advantage:  Precision  Macro            Challenges:  ProducAon     &  Micro  Structures                                  Scale-­‐up  and  Costs   28-­‐31  August  2006  

hBp://www.mezzotech.com/  

Kevin  Kelly,  formerly  Mechanical  Engineering  


Microfabrication Industrial  Partners Applications – precision mechanical Parts,  micro  features  –  accelerometer,  switches,  springs,   shuiers   Prototype   Proof-­‐of-­‐Concept  

Op&mized   Design  

Produc&on   Packaged  Product  

hBp://www.htmicro.com/  

Jost  GoeBert,  Director,  Microfabrica&on  


Microfabrication Industrial  Partners Creatv  MicroTech   Ultra-­‐tall,  High  Aspect  Ra&o  Microstructures   hBp://www.creatvmicrotech.com/  

An&-­‐scaBer  Grid  for  Medical  Imaging    Applica&ons  

1.5  mm  deep  and  25  µm   wide    microchannels  in   PMMA    

1.8  mm  thick  gold   an&-­‐scaBer  grid,  25   µm  septa  

Gold  mask,  25  µm  wide   and  2000  µm  long  slits,   150-­‐160  µm  thick.   Copper collimator with 25 µm wide septa

Gold  mask,  29  µm  wide   and  3000  µm  long  slits,   200  µm  thick.   Stacked  lead  collimator,  2.0  cm   tall,  130  µm  septa    

Jost  GoeBert,  Director,  Microfabrica&on  


Microfabrication Industrial  Partners MicroMo&on   Compact  Micro-­‐Motors  for  Posi&oning  Applica&ons   Semicon Flexspline

Flexspline

Output bearing

Optical Communication

Planet gear

Flexspline Output flange

Dynamic Spline Circular Spline

Dynamic Spline Flexspline

Robotics Motor Dynamic Spline Circular Spline Sun gear

Planet gear Housing Planet gear

Micromotor with Gearbox

Measuring Machines Microscopes/Biotech hBp://www.mikrogetriebe.de/sites/english/about-­‐us.html  

Space

m  i  c  r  o  re     s  i  st   t  e  c  h  n  o  l  o  g  y  

Jost  GoeBert,  Director,  Microfabrica&on  


What we do at CAMD