Nano Biosols goldblog

nanoparticles for biological solutions

Gold nanoparticles, Covid and Rapid Tests

The science behind Prime Minister Boris Johnson’s “moonshot” project in dealing with Covid19 is actually doable. i.e. cheap disposable tests taking 20 minutes rather than expensive lab-based PCR tests that take several hours. The problem is sensitivity. Rapid antigen tests as they are called are already in use for diseases where sensitivity is not a problem. There are now commercial rapid antigen test kits for covid19 on the market already. The UK is currently trialling some of these tests in a mass testing exercise in Liverpool. They can detect around a minimum of about 105 virions/ml compared to 102 / ml for PCR. The range in patients can be from 102 to 1011 per ml depending on the period after infection (roughly day 3 to day 20). The key material in these rapid tests is antibody labelled gold nanoparticles that detect a viral protein and show up as a red line when the test is positive, just like pregnancy tests.
Public Health England stipulated that tests had to have 98% specificity and sensitivity to be useful. Many rapid tests are only 70-80% sensitive. However, it is known that as the viral load of patients’ increases over a period of days to its peak, it is detectable by rapid tests. This provides a window of opportunity for the tests to be useful, but testing every few days would be required to catch the peak in asymptomatic people. A recent publication modelling high-frequency use of cheap less sensitive tests states it is likely to be more beneficial than expensive slow PCR tests with all the bottlenecks we have observed.*
A delayed PCR test result is not much use in preventing spreading of the disease. The paper suggests rapid testing could be used as an initial mass screening approach reducing the demand for PCR testing in the first instance and thus allowing PCR confirmation of patients with ambiguous results that could be false positive or false negative depending on their symptoms status. Mass testing with rapid tests would also pick up a percentage of asymptomatic infectious people if they were in the peak phase of viral replication. Positive testing asymptomatic individuals could then have a confirmatory PCR test.
In summary, the rapid tests are very useful for detecting the virus at peak viral load when an individual is most infectious regardless of symptoms. It may lead to false negatives if tested too early in the cycle, or false positives which all diagnostic tests suffer from, but at very low levels. Meanwhile, the debate about which days you are actually infectious goes on. It is generally assumed to be days 3 to 10 post-infection. Regular testing every few days would help mitigate this problem.

* https://doi.org/10.1101/2020.09.01.20184713

Nano Biosols provides a service to prepare custom conjugated gold nanoparticles with the antibody of your choice for rapid test development or research purposes. We are happy to make small scale batches for pilot studies.

10/11/2020 Posted by | Category 1 | Leave a Comment

Nanomaterials workshop March 2020

This #NANO Training programme has been carefully designed to offer the required knowledge and professional skills sets: A – Fundamentals & Basic Concepts: Knowledge-based B – Advanced Technology Applications: Knowledge & Technical skills (Hands-on session)

 

 

23/01/2020 Posted by | Category 1 | Leave a Comment

Video of Quanti Gold kit and how to use it. No need for mass spectrometry

The Quanti Gold kit is used to quantify gold nanoparticles in a sample, either in cells or solutions.

Originally developed to quantify cellular uptake of gold without the use of mass spectrometry it can also be used to optimise your methodology for preparing your own gold conjugates, measure performance and quality control for monitoring shelf life.  Watch the video here  https://youtu.be/vybMuk8O8CM

23/01/2020 Posted by | Category 1 | Leave a Comment

Nanomaterials workshop

The first joint workshop between Nano Biosols and Shimyatech on nanomaterials and their applications held at Liverpool Science Park was a great success. This was an initial attempt to create a nano network in the area between business and academia and encourage interested parties to learn more about the versatility of nanotechnology that encompasses everything from printed electronics to diagnostic tests for cancer. A practical demonstration of some of the properties of nanoparticles was well received.

26/11/2019 Posted by | Category 1 | Leave a Comment

Quantification kits for cellular uptake of gold nanoparticles

One of the key problems with researching into the effects of gold nanoparticles on cells is the quantification of the nanoparticle uptake by the cells.

Without solid data on the number of particles taken up, it is difficult to work out the efficacy of the particles on any observed effect.

The most sensitive method involves ICP-MS  mass spectrometry. An alternative is ICP-OAS. Both these methods may involve complex sample preparation (use of concentrated acids), both are expensive regarding hardware required (£100,000 plus) and ongoing running costs. Many labs will not be able to buy and run their own facility so will rely on accessing their institute’s serviced facility at a cost.

An alternative lab-based simple method without the need for expensive equipment would be very useful as a “screening method” for initial pilot studies to optimise cell uptake studies. Such a method has been developed in our R and D labs, and is available as the “Quanti-Gold kit”.

All that is required is a smartphone to record a digital image of the data and an internet link to access the free download of Image J software to calculate the gold content.

It has a sensitivity of approximately 106 nanoparticles per µl of a sample which approximates to 10 atto moles of gold nanoparticles.

The kit can be bought in 100 ml or 200ml sizes or as “combo kits” with either gold nanoparticles for your own conjugations or with custom conjugates at discounted prices.

23/08/2019 Posted by | Category 1 | Leave a Comment

Assaying blood samples for circulating cancer cells: a new application for gold nanoparticles.

A recently published paper (https://doi.org/10.1038/s41467-018-07214-w) by researchers at the University of Queensland describes  how gold nanoparticles can be used to develop a simple 10 minute blood test for the detection of circulating cancer cells DNA. The test involves initially purifying DNA from the cells in the blood sample.The assay is based on the observation that cancer cell DNA is methylated in a different way compared to normal cell DNA. It was noticed that this allowed the cancer cell DNA to bind to gold metal surfaces and could stabilise gold nanoparticles, unlike normal genomic DNA. The researchers then took advantage of the well-known phenomenon that stable gold particles appear a pink/red colour whereas aggregated gold particles turn blue/grey and can sediment. By adding a high salt buffer the particles would aggregate and turn blue if no cancer DNA was present but remain pinkish/red if the stabilising cancer DNA was present. The test doesn’t define the type of cancer but could be used as a simple pre-screen test as samples from different cancer types proved positive with a success rate of 90%. This is a remarkable finding and shows the simplicity and versatility of gold nanoparticle technology keeps on developing new applications. This example shows how the incredibly complex task of distinguishing cancer cell DNA from normal DNA in a blood sample can be achieved  so simply with a bit of lateral thinking and understanding of the properties of gold nanoparticles. There are probably many more problems out there waiting for a simple solution that gold nanotechnology may provide.

11/12/2018 Posted by | Category 1 | Leave a Comment

Silver enhancement increases sensitivity by at least a hundredfold

Gold nanoparticles are used routinely in hundreds of assays known as lateral flow or “flow through” assays. The main properties are that they are cheap and give a clear red visual image when an assay gives a positive result. They are incorporated into simple disposable tests that do not require sophisticated equipment.

The main disadvantage is that they may not be as sensitive as other methods. If the analyte in question is a nucleic acid, then this type of analyte can be amplified by PCR or LAMP amplification techniques. If the analyte is a protein or molecule detected by an antibody then the only way to increase the sensitivity is by modifying the detection method to be more sensitive.

With gold nanoprobes this increase in sensitivity can be achieved by silver enhancement, which can increase the sensitivity a hundredfold. In addition the silver enhancement produces a black stain giving a greater contrast in colour making it much easier to confirm a positive result.

If you are developing gold based assays and want at least a hundred fold increase in sensitivity then try our Silver Stain kit.

 Example.

Gold particles (10 nm) were dotted in 1µl volumes at tenfold dilutions from 20 femtomoles  (12 x 10particles/dot) to 20 attomoles (12 x 106 particles/dot) on nitrocellulose. After blocking and rinsing in water the dots were incubated with our Silver Stain kit for 10 minutes.

Result. The top row is silver enhanced gold dots decreasing in concentration from the left. The lower row is just the gold dots at the same concentration The second dot of unstained gold is barely visible at this concentration but when silver stained it is clearly visible and the sensitivity increase is clearly at least a hundredfold and of greater contrast

20 fM   2 fM       0.2 fM     20 aM     Control

An excellent review of quantitative biosensing applications of silver enhanced gold nanoparticles can be found at

http://dx.doi.org/10.1080/05704928.2013.807817

12/04/2018 Posted by | Category 1 | Leave a Comment

Nanoparticle User Survey

If you use nanoparticles in your work or research, we would be pleased to hear your opinions on the concept of a nanoparticle users exchange shop.  This is where lab staff can make their validated reagents available to other users for a price. This service would encourage greater use of niche products not commonly available commercially, less risk as they would be validated and also lead to  more useful research data generated. A nanoparticle exchange facility based on the sharing economy would lead to more data generation and less “reinventing the wheel.”

Complete the short survey at https://goo.gl/forms/6BTDFvasADXYNEXD2

11/10/2017 Posted by | Category 1 | Leave a Comment

Nanomedicine and its delivery problem.

A recent paper by the Chan group in Toronto reviewed the data from published articles on delivery of nanoparticles to tumors over the last decade and found it was not a very efficient process. The median delivery efficiency was as low as 0.7% of an injected dose

http://dx.doi.org/10.1038/natrevmats.2016.14

An excellent article in Chemical and Engineering News discusses the implications of the papers findings with experts in the field highlighting both positive and negative views. The important message is that we need to know how many particles reach their target so that methods to improve nanoparticle design for better delivery can proceed.

http://cen.acs.org/content/cen/articles/94/i25/Does-nanomedicine-delivery-problem.html

What is clear is that for nanomedicine to become a reality, then methods for real time quantification and imaging of nanoparticles  in vivo is required to measure their efficacy. One method applicable to targeting gold nanoparticle is the iodine isotope chemisorption method outlined in our publication    http://rdcu.be/tTwL

24/08/2017 Posted by | Category 1 | Leave a Comment

Real time quantification of gold nanoparticles in experimental use. As simple as plug and play.

The main problem with using gold nanoparticles in life science research is the lack of a simple real time quantification method. Use of mass spectrometry is very accurate but also very expensive and definitely not in real time. It is now possible to quantify gold nanoparticles in real time in experimental procedures by using the chemisorption of Iodine -125 to the gold particles. This simple labelling step involves just mixing the two components. Take your functionalised gold particles and add the isotope. As simple as plug and play. Applications include quantifying in-vitro cell uptake of particles and the potential for imaging in-vivo small animal particle distribution using SPECT (I-125) or PET (I-124) procedures. If nanomedicine is to become a reality, then simple real time methods of imaging and quantification need to be developed. Silver nanoparticles can also be quantified by this method also. Details of our work in understanding the chemistry can be found in a recent publication of the Journal of Nanoparticle Research.         http://rdcu.be/tTwL

03/07/2017 Posted by | Quantification | Leave a Comment