2010 in review

The stats helper monkeys at WordPress.com mulled over how this blog did in 2010, and here’s a high level summary of its overall blog health:

The Blog-Health-o-Meter™ reads Fresher than ever.

Crunchy numbers

The average container ship can carry about 4,500 containers. This blog was viewed about 15,000 times in 2010. If each view were a shipping container, your blog would have filled about 3 fully loaded ships.

In 2010, there were 27 new posts, growing the total archive of this blog to 67 posts. There were 7 pictures uploaded, taking up a total of 344kb.

The busiest day of the year was April 26th with 109 views. The most popular post that day was Resources .

Where did they come from?

The top referring sites in 2010 were linkedin.com, en.wordpress.com, biosensorforum.com, google.com, and search.conduit.com.

Some visitors came searching, mostly for influenza b, bio barcode, lateral flow immunoassay, flu virus, and biobarcode.

Attractions in 2010

These are the posts and pages that got the most views in 2010.

1

Resources May 2009
5 comments

2

Gold Nanoparticles: Worth their Weight in Gold! June 2009
4 comments

3

Biosensors May 2009
5 comments

4

About April 2009
6 comments

5

NanoSensors: Nanoparticles as Chemo/Bio Sensors September 2009

New Technology Platforms for Diagnostics Applications

 

Prof. Abraham Lee was the second speaker of the day and talked about using Microfluidic Acoustic Cavity Transducers or in simple terms using air bubbles for mixing in microfluidics channels. Bubbles can enhance mixing and increase the kinetics of the binding. A log order improvement is seen in proof-of-concept immunoassays and significant improvement is seen when these type of mixing were applied to protein arrays. The protein array work was done in collaboration with from Felgner lab. There is a company (can’t remember the name) that can mix liquids in small drops for mixing and speeding up the diffusion.

Prof. Mike Sailor followed Prof. Lee and he talked about using porous silicon nanostructures for in-vitro and in-vivo diagnostics application. These silicon nanostructures have different light reflectance properties based on their nanoporous structures. He gave example of Abalone shells that are iridescent because of similar phenomenon.

Abalone Shell (credit Wikipedia)

The optical properties of thin film of porous silicon nanostructures changes based on how these nanopores fill up with liquids or small protein fragments and can be used for biosensing applications. One biological example he talked about was using this for protease assays. In presence of protease, casein is cleaved into small fragments that can fill up the pores and hence change the optical properties of the silicon nanopore sensor. These nanoporous structures can be lift-off from thin film structures and these micron sized particles act as spectrally encoded particles and can be used for multiplexed biosensing. These micron sized particles can be sonicated and broken into nano sized particle and can be used for in-vivo imaging. Some of his papers available on Google Scholar are here. Biomolecular screening with encoded porous photonic crystals and Biosensing Using Porous Silicon Double-Layer Interferometers and Biomimetic amplification of nanoparticle homing to tumors — PNAS.

 

Point-of-Care Diagnostics for the Developing and Developed World

Continuing on my views on Future Diagnostics Company-John Carrano of Carrano Consulting LLC was the first speaker of the day talking about POCs and global trends. Key points he raised

• Driver of POCs are: Reducing cost, accessibility, lowering mortality and improving National security.
• Mass customization, miniaturization, convergence, and wireless are the global trends.
• There is a need for the standards: Instrument standards (performance, measurement methodologies and data presentation); Interface standards (hardware and software); device and material standards and country standards.
• Five attributes of success: portability for deployment in low infrastructure settings; speed (<1hr); accuracy (specificity, sensitivity); multiplexing; and cost.

Nothing new that is not known already!

Proteomics and Diagnostics: Live from Future Diagnostics Conference

 

Prof. Samir M. Hanash and Prof. Emanuel F. Petricoin highlighted the way proteomics research is changing the way future diagnostic tools will be developed. The pathway specific multiplexed assays, multicentric large cohort studies to validate biomarkers, autoantibody detection against cancer specific antigens are some of the topics that were discussed during these talks. Prof. Hanash stressed on importance of having biological samples from large population over several years so that relevant biomarkers could be identified that will have predictive value before cancer appears. Prof. Petricoin discussed reverse phase protein arrays and their development as diagnostic tools by Theranostics Health.

Overall very interesting talks.

Bead Arrays and Single Molecule Detection Technologies

 

Had a great productive day at Future Diagnostics Conference. First talk was by Prof David R. Walt of Tufts University on Bead Arrays and Single Molecule Detection. Prof. Walt is one of the founders of Illumina, the DNA array company. He talked about the Illumina technology but the more exciting was the new technology platform he is developing for single molecule array or Single Molecule Array (SiMoA™). He has founded another company, Quanterix, that is developing this technology for protein detections in blood. The assay, according to Prof. Walt is so sensitive that he used a term I had never heard of before. The Limit of detection (LOD) of the SiMoA is 22 yoctomole (yoctomole = 10^-24 mole)-I guess everyday is a learning day. I will look forward to the day when this technology will change the way we do immunoassay.

Live from UC Irvine: Future Diagnostics Conference

 

April has been a crazy month with lots of deadlines and projects and as a result I haven’t been able to update my Blog. However, I do have bunch of papers printed and neatly stacked that I will try to cover in next few weeks or so. I am right now attending a conference at UC Irvine on Future Diagnostics platform. Several interesting talks both on the new technologies in the pipeline as well as one really interesting talk about bottlenecks in introducing new technologies to clinical lab setting. I will summarize some of the talks and their relevance to the Biosensor research later today.

 

Bits and Pieces: 032810

An Excellent Review on Microfluidics Applications of Magnetic Particles

I have written often on various bio-analytical applications of magnetic particles and microfluidics. So, I was very excited when a visitor to my blog sent me a copy of an excellent review on Microfluidic applications of magnetic particles for biological analysis and catalysis. The best part of the review is close to 500 references covering everything from a) synthesis of magnetic nano/microparticles; b) functionalization of these particles to attach bio-molecules; c) designing microfluidic channels to manipulate magnetic particles and; d) large number of applications that combine convenience of handling magnetic particles with microfluidics.

The review discusses four important biological applications including cell handling and separation, nucleic acid processing and detection, immunoassays, and catalysis. Commercial applications including Philips’ magnetic biosensor platform and MACS (Magnetic Cell Sorting) is also covered but a notable commercial application missing from the review was the Bio-Barcode nucleic acid detection platform developed by Chad Mirkin and commercialized by Nanosphere.

Overall an excellent review coming at the right time!

Seawater Desalination and Biosensors

Continuing on the theme of microfluidics, while doing my end of the week scan of articles related to biosensor I came across an article on Direct seawater desalination by ion concentration polarization. The article describes a small to medium scale sea water purification device by using a phenomenon called “ion concentration polarization (ICP)”. Even after carefully going over the article couple of times I am still not very clear about the phenomenon but was attracted by the fact that the desalination method is a membraneless process and is implemented in a microfluidic platform. The device pushes both salts and larger particles (cells, viruses and microorganisms) into one channel and pure potable water is separated into a separate channel. While reading the article I thought maybe the same method can be used to concentrate analytes in biological samples before measuring them using biosensors. In addition since ICP separates charged species may be it can be used to further separate analytes based on charge that may be useful to fractionate samples before analysis!

Just a thought!

Another Listmania: Companies offering novel assays/assay platforms

I keep on coming across several companies offering or developing tests (mostly diagnostics) that are not based on conventional ELISAs or Lateral Flow Immunoassays (a.k.a Dip stick tests or Rapid diagnostic tests (RDTs)). Some of these companies are offering multiplexed assays or multiplexed assay platforms. Protein arrays, DNA arrays, bead arrays are just some the platforms being developed by these companies.

I thought why not make a list of such companies. So here goes the initial list-just few companies but this will grow with time. Send me names of other companies that you think are worth including in this list.

Click here for PDF file with clickable links (Updated March 23, 2010)

Folding based Biosensors

For a while I have been planning to write about biosensors that have been called names like genetically encoded biosensors, protein complementation biosensors, folding based biosensors etc. The biological elements in these biosensors can be proteins, DNA, or aptamers. Binding of specific ligand induces a change in structure of the biological molecule resulting in a signal that can be optical or electrical. What finally triggered me to write about these types of biosensor is an excellent overview on folding based biosensor by Kevin W. Plaxco of UCSB.

In this post I will only talk about folding based biosensors and will touch on other biosensors in later posts. To best understand folding based biosensors take a look at the schematic that I got from Prof. Plaxco website.

Credit: Prof. Kevin W. Plaxco; University of California. Santa Barbara

The DNA/aptamer probe is modified with the redoxable methylene blue (MB) moiety at one end (other tags can be used too!), and is attached to the gold working electrode at the other end via gold-thiol linkage. Upon target binding, the probe can either fold so that MB comes close to the electrode, increasing the efficiency of electrons transfer from the MB tag to the electrode, thereby producing proportional increase in current. It can also happen other ways where probe is already folded and will unfold on binding of target hence decreasing the current. These sensors are essentially label free sensors.

Want to know more about these sensors? I have put links to publications that I found on Google Scholar

1. Reagentless transduction of DNA hybridization into a readily detectable electrochemical signal

2003 paper in PNAS describing the concept of folding based biosensors for picomolar level detection of DNA

1. Monitoring of Cocaine using Electrochemical Aptamer-Based Sensor

2009 paper in JACS on detecting low micromolar level cocaine detection using folding based biosensors integrated with microfluidics.

1. Optical Sensors Based on the Binding-Induced Folding of Proteins and Polypeptides

2009 paper in Chemistry describing folding based biosensors inducing change in optical properties rather than electrical properties

1. Better Living Through Biosensors

A really nice powerpoint presentation by Prof. Plaxco

As I was writing about this post I thought of my previous post on multiplexed CombiMatrix platform. Hey! can this biosensor be put on Combimatrix platform-will be a cool technology!

Multiplexed Immunoassay on CombiMatrix CMOS Array

CombiMatrix’s CMOS arrays have 12,544 individually addressable electrodes that have been used for design of DNA chips for variety of applications including Influenza detection, human cancer research, and for spotting whole genome of several fungal species. Multiplexed immunoassays have also been developed on this platform by two different methods; a) linking antibodies with complementary DNA sequences that can be captured on specific electrodes containing complementary DNA sequence and b) biotinylated antibodies captured on streptavidin coated electrodes. However, antibodies being antibodies they are fragile at the electrodes and conjugated antibodies are difficult to produce reliably-this according to authors of recent paper in PLoS ONE. They have come up with a new method where they electrochemically deposit ‘protein friendly’ polypyrrole (Ppy) on selected electrodes followed by adsorption of antibodies on Ppy layers. For detection, they use sandwich immunoassay with Cy5 labeled 2^nd antibody for fluorescent detection and HRP labeled 2^nd Ab for enzyme enhanced electrochemical detection (ECD). Limit of detection (LOD) between 0.003 and 0.01pg/ml was achieved using ECD method.

Although, Ppy can be individually addressed on the electrodes, antibody adsorption is done using traditional spotting methods. In that sense this method is no different from traditional antibody arrays with fluorescent detection, with claimed LODs of sub pg/ml levels, except for ECD detection method.