We have a winner!
The inventors have picked Ischemic vs. hemorrhagic stroke by Mitchell Wold
as their winner for this competition. Here's what they had to say:
"While in a tough diagnostics field, Mitchell's idea really ticks all of our boxes.
We have existing (if somewhat unproven) antibodies, an underserved market with a significant need (if you can save insurers the use of a CT/MRI scan AND improve medical outcomes by allowing quick disambiguation between strokes or other sources of dizziness then it is a win/win), and the need for a mobile, multiplexed and quantitative system.
Interestingly, Biosite tried to do it, then pulled the test. While obviously indicating some difficulties in pulling this off, it also demonstrates a recognised commercial potential.
We'd like to give a special mention to Eswar for a) the serious amount of work he's put in and b) the most lateral idea of all the submissions - really enjoyed thinking about his perfume idea."
The bottom line
: We're looking for a large enough market to justify manufacturing setup and regulatory costs where consumers would be prepared to pay $15+ per test. The unique features to exploit are multiplexing of dozens of quantitive tests combined with rapid & simple point-of-care use with minimal sample prep – carefully check out the full comparison to competing methods in the table below.
The vast majority of biosensors today are based on some form of optical readout to get the results you want. You usually have a choice between inexpensive (but non-quantitative) methods such as lateral flow tests (e.g. pregnancy tests), which just show you a blue line if positive, or more sensitive tests that can tell you how much of the analyte is present using specialised optical equipment. These quantitative tests generally require several extra wash steps and additional reagents and are carried out by labs or on specialised microfluidic or robotic platforms. We wanted to develop a sensitive, quantitative technology that doesn’t require expensive platforms but instead:
How the e-Gnosis system will work: a small chip with the ability to test for dozens of analytes slots into a reusable reader, which in turn connects to a smartphone, computer or tablet.
- Could be read using a low-cost smartphone or laptop accessory (<$20);
- Works with a small amount of sample (~10 microlitre, such as a tiny drop of blood, urine or saliva)
- Requires no (or just one) washing steps.
- Runs several different tests on the same sample simultaneously.
- Is as easy to use as a pregnancy test.
And that’s what we’ve done with our e-Gnosis chip! We’re now looking for both attractive markets in the medical diagnostics space or in the potentially much easier to enter consumer space. Please read the “Your mission” section below carefully!
The table below compares our device to existing test categories. The e-Gnosis chip combines the advantages of quantitative, multiplexed tests with the accessibility of a low-cost, mobile reader – which should make it very attractive to consumer applications. However we need to find one where we can reach high volumes to justify setup costs and where a cost of goods sold of $6-8 per test is realistic.
We’re looking to find a market that is large and has less regulatory tape than medical diagnostics
We’ve been looking at the field of medical diagnostics for a while, but the point-of-care market is highly competitive, fragmented into relatively small markets, with high entry barriers in the form of FDA/EMA approval. So for any medical diagnostic we’d need a large market, where our device’s unique features (multiplexing, rapid & simple point-of-care use without sample prep) offer a very significant competitive advantage, and can justify the high barrier costs for approval.
We’d be very interested to hear ideas about a consumer market to prove the device commercially, keeping in mind:
- While the chip-manufacturing part of the process is cheap, the cost/test is unlikely to ever fall below $6-8 due to functionalization and assembly. We need an application where customers would pay enough to allow a reasonable profit margin.
- Need a high-volume application to justify setup costs of chip-manufacture (>$300k). What’s your market size?
- What would be the market entry route? Who’d be our commercial partners? What are the competing devices and their price? How would distinguish ourselves against these?
We have so far proven the concept and are now working on simplifying the chip and applying to existing assay (pregnancy tests first). We think immunoassays in general are a good starting point, as they do not require complex sample preparation. Other assay types are possible as well though (see Key Features below or the background section above).
A large variety of existing immunoassays (and other tests) can be moved onto the e-Gnosis chip surface, including:
- Allergies (by looking for antigen specific IgE's in a multiplexed assay, currently done by companies such as Phadia)
- Cancer (e.g. Prostate-specific antigen)
- Infectious disease
- Stress testing (using cortisol, testosterone and alpha amylase).
- Detection based on large variety of probe-analyte interactions
- complimentary DNA strands
- Note: For very small molecules, a competitive assay format or secondary antibodies have to be used to cause a large-enough constriction of the pores.
- Low-cost, low-power mobile reader, size of a USB thumb drive (~20 $ cost)
- Robust & simple to use: direct electrochemical readout, less components and steps than optical methods
- Multiplexed: 3x3 mm chip could easily run 25 tests in triplicate
- Quantitative & sensitive: In trial detected streptavidin (using biotin as a probe) down to 5x10-11 M, and accurately determined the size of streptavidin (about 5 nm). Potential for further improvement.
- Scalable technology using existing semiconductor fabrication front-end: fabrication can be outsourced.
Curious about all the clever science that is making the e-Gnosis chip work? Click here for the in-depth explanation.
Schematic of the operating principle of the e-Gnosis chip. Click to enlarge.
Here’s how it works:
Two electrodes running at right angles to each other are separated by an insulator (silicon oxide, shown in yellow below). Hundreds of thousands of nanometre sized wells (we call them nanowells) are formed through this structure (via CsCl island lithography
), so that one electrode is at the bottom, and the other at the top of the wells. The wells are ~ 100 nm in diameter, and around 200 nm deep (although these dimensions can be varied). The area where the top and bottom electrodes overlap is what we call a pixel, and each pixel is in essence a huge array of nanoelectrodes with a very small electrode spacing. Arrays of nanoelectrodes have many advantages over macroelectrodes of equivalent electrode surface area, chiefly a higher signal to noise ratio and therefore a lower limit of detection in electrochemical analysis (Prof. Madou has some great lecture slides on electrochemistry and scaling
). Our chip could be used for tests such as the quantitation of pharmaceutical metabolites in urine, so if you have an idea for a electrochemical based test, let us know!
We go one step further and rather than analysing electrochemical reactions, measure the binding of an analyte molecule (could be a pregnancy hormone, cancer marker etc) to a probe molecule (e.g. an antibody).
We stick probe molecules (we have used biotin to bind streptavidin, but now are working on using antibodies), which bind the analyte we are looking for, to the inside of the pores. We then place a droplet of sample together with a redox couple (e.g. Ferri/Ferrocyanide) on the chip and apply a voltage. The redox couple is oxidised at one electrode, diffuses over to the other electrode and is reduced there. This results in a steady state where the current that can flow between the electrodes is dependent on the diameter of the nanowells. If the molecules we are looking for are present in the solution, they bind to their complementary probe molecule, and reduce the diameter of the nanowells and therefore the current that can flow between the electrodes at a given voltage. The rate of the current drop allows us to deduce the analyte’s concentration. We can also do the reverse, where the pores’ opening-up creates the signal, e.g. by attaching enzyme-degradable peptides to the pore walls. Competitive immunoassays are another possibility.
In order to prevent the electrodes from fouling over time, we frequently inverse the potential applied to the electrodes, which has a cleaning effect and makes sure the signal change we see is from the binding to the inside of the wells and not from non-specific adsorption to the electrodes. We also use control pixels that do not have active probe molecules and so cannot bind to anything specifically, but have the same functionalisation as the active test pixels. These control pixels provide a background signal. By subtracting the control pixel signal from an active pixel signal we get the signal change due to a specific binding reaction.
We currently have a chip with just twelve pixels, but at production scale, it's possible to fit in excess of 100 pixels on a 3x3 mm chip, each of which can in theory detect a different compound.
I’m Peter Kollensperger and I’m working with Prof. Green in the Optical and Semiconductor Devices Group of the Electrical and Electronic Engineering Department at Imperial College London.
My research to date has focused on the use of nanotechnology for biosensing applications, but my overarching interest is in making diagnostic/sensing technologies more accessible both to doctors and the general public.
The combination of scalable nanotechnology and the hugely parallel processing of semiconductor foundries holds great promise for the area of biosensors and we are looking for applications where the end-user wants to get results on the go without spending a large upfront amount on a reader. This can be in medical diagnostics, but ideally would be in an underserved consumer market where the combination of properties of our chip can make a real difference.
CsCl island lithography
The Analytical Applications of Square Wave Voltammetry on Pharmaceutical Analysis
Youtube video: Enzyme-linked immunoassays (ELISA)
Direct & indirect ELISA Animation
On the positive effects of downscaling in electrochemistry