Interview conducted by Skyla BailyNov 25 2022
At MEDICA 2022, NewsMedical spoke with Andy Chaloner astir Stream Bio's conjugated polymer nanoparticle technologies that person the imaginable to revolutionize the aesculapian and beingness sciences sectors, from diagnostics to objective imaging.
Please could you present yourself and your relation astatine Stream Bio?
I'm the CEO of Stream Bio. We've been astir for astir four or 5 years now, but we've lone conscionable travel to the commercialized marketplace decently successful the past 12 months. Prior to that, we concentrated connected R&D.
What is Stream Bio and what commercialized technologies does it produce?
What we person is simply a marque new, caller fluorescent reagent for the beingness subject market, concentrating the concern strategy successful 3 areas: the reagents market, diagnostics, and successful the longer-term, quality objective imaging. We've got collaborations connected the spell with assorted universities, aesculapian schools, and manufacture partners.
Stream Bio leverage conjugated polymer nanoparticles (CPNs) with extended potential. What are CPNs and what drives the request for them successful the aesculapian and beingness subject industries?
What we person is simply a polymer equivalent to quantum dots lone overmuch brighter. The inventor of our merchandise is Professor Mark Green astatine King's College University, and he's primitively a quantum dot idiosyncratic by trade. When they started putting quantum dots into biologic cells, helium recognized the limitations of the toxicity and began to look for an alternative.
Image Credit: Stream Bio
He looked astatine the conjugated polymers you find wrong OLED TV screens and fundamentally what we person is different particle wherever the polymer concatenation is scrunched up into a ball. There’s a capping cause astir the aboveground with a full scope of carboxylic groups, and we tin accommodate the aboveground chemistry. So we've got maleimide, carboxylic, thiol, amine, alkene, and assorted kinds of chemistries we tin connect antibodies, oligos, and virtually thing other to, and we tin past usage it successful virtually immoderate beingness subject application: lateral flows, ELISA, occidental blot, microscopy, you sanction it.
We fundamentally beryllium astatine the halfway of a Venn diagram betwixt physics, chemistry, and biology. The particles are birthed successful physics, made successful chemistry, and their applications are successful biology.
What was the probe and improvement process similar for these particles?
We spun Stream Bio retired of King's College London, and we inactive person precise beardown ties with them. We took it to the government's high-value manufacturing catapult, and with the Formulation Center astatine the Centre for Process Innovation, we turned what was made successful a beaker connected a seat into an industrial-scale manufacturing process wherever we tin manufacture precise ample quantities. That took astir 18 months, and astatine the extremity of it, we had a manufacturing process, 4 colors, and 1 aboveground chemistry.
Image Credit: Stream Bio
We won an Institute of Physics Business Start-up and Innovation Award successful 2018, and connected the backmost of the enactment with the CPI and the award, we won backing from Innovate UK successful 1 of their archetypal rounds of the UK Loan Competition. We got astir a 3rd of a cardinal pounds and then, implicit 2 years, we developed the exertion from 4 colors to sixteen, each the mode up to the infrared (1000nm), and we person astir 5 aboveground chemistries and 2 types of accelerated conjugation kits for antibodies and oligos, each of which has just precocious travel to marketplace successful the past 12 months.
While we've been doing each of that, we've evidently been fostering collaborations with assorted universities to physique the information bundle and besides to look somewhat longer-term.
The CPNs you person developed person been tested for usage successful accelerated lateral travel tests. How tin these particles amended the usage and ratio of these tests?
COVID came on and we ever knew the particles would beryllium exceptionally bully astatine diagnostics, truthful we collaborated connected and developed a lateral travel test.
We tested the unoptimized lateral travel against assorted variants astatine Nottingham aesculapian schoolhouse and got down to TCID50 little than 100 which is equivalent to astir 30 to 35 cycles connected PCR. So we efficaciously person PCR sensitivity successful a point-of-care test.
Multi-colored LFTs utilizing CPN 830, CPN 770, CPN 610 & CPN 660 to observe ovalbumin. Image Credit: Stream Bio
Now, we've formally teamed up with RapidIVD, who are a declaration lateral travel developer. They tin spot the monolithic payment successful these particles going forward, truthful present 1 constituent of our concern is processing lateral travel tests with RapidIVD utilizing our particles.
What is it astir your particles that marque lateral travel tests truthful overmuch much delicate compared to those we are acquainted with?
Standard ocular lateral travel tests usage colloidal gold, which is simply a modular reddish color, oregon latex beads, and they're constricted to a definite level of sensitivity. Our polymers person exceptionally precocious absorbent coefficients and tin beryllium visually work to a higher sensitivity. They are besides fluorescent erstwhile excited astatine the close wavelength. With fluorescence, radical deliberation brightness is ever measured by quantum yield, but it is really quantum output times extinction coefficient. So if you privation to get into the physics of it, the polymers sorb an exceptionally precocious magnitude of photons and past footwear retired an mean magnitude out, and it's that extinction coefficient that makes them exceptionally agleam and exceptionally absorbent. We did a examination astatine UCLA against quantum dots and were 1000 times brighter, and against colloidal golden we were 40% much absorbent.
Lateral travel strips nutrient stronger signals than europium chelate successful a LFT for influenza A. Image Credit: Stream Bio
In a ocular lateral travel nether mean ambient light, we tin present multicolored lateral travel tests, beyond reddish and blue. Imagine a trial with 4 antithetic colors giving 4 antithetic targets, oregon a postulation airy strategy of the severity of corruption connected 1 strip.
If you past enactment it successful a somewhat darkened country oregon you conscionable excite it with the close excitation successful a scholar it past fluoresces. So the aforesaid particle does ambient colour and fluorescence.
A batch of fluorescent lateral flows that are connected the marketplace usage europium. We did a head-to-head examination with europium successful a flu A and flu B, and we were a 100 times much sensitive. So we tin beryllium utilized successful ocular ambient airy oregon fluorescence, we're 40% much absorbent than gold, a 100 times much delicate than europium successful a flu A and flu B test, and we've got a COVID trial which demonstrated successful 10 minutes PCR sensitivity.
Limit of detection of CPN-based SARS-CoV-2 lateral travel tests⁴. Clear awesome seen to TCID⁵⁰ = 100 by the Stream’s LFT reader. Image Credit: Stream Bio
What are immoderate of the different applications of CPNs wrong diagnostics?
The CPNs tin beryllium applied anyplace successful diagnostics that necessitate a ocular oregon fluorescent label. We're besides processing a scholar with an manufacture spouse with a unsocial camera that takes a photograph of the power and the trial enactment and past integrates the fluorescent awesome utilizing an progressive imaging camera.
The scholar we are processing which is astatine an precocious prototype stage, is handheld, weighs a kilo and a half, waterproof, driblet proof, and we tin accommodate it with Wi-Fi, GPS, and 5G capableness with a six-hour rechargeable battery. Ideal for point-of-care successful immoderate environment.
You person precocious enactment retired a property merchandise announcing the motorboat of your LINKBRIGHT accelerated conjugation kits with Sigma-Aldrich arsenic distributor. With the motorboat of these kits, however has this expanded the scope of your CPNs’ commercialized applications?
With this launch, we person released each 16 colors, each aboveground chemistries, and the LINKBRIGHT kits, each of which are present disposable done Sigma-Aldrich.
With the kits, we person created a accelerated conjugation capableness wherever we pre-activate the particles. So if idiosyncratic wanted to bash it comparatively quickly, they tin beryllium done wrong 30 minutes.
The value of Sigma-Aldrich is that it means our exertion is present disposable worldwide done Sigma's organisation strategy with their promotional and logistical capableness to backmost it up. A batch of companies and universities would automatically spell to Sigma, truthful it gives america a worldwide outlet.
Glioblastoma crab cells were labelled with CPN 680 (orange) for 24 hours successful vitro and past implanted into the chick embryo chorioallantoic membrane astatine embryonic time 7. Tumours were dissected from the embryo astatine embryonic time 14, frozen and sectioned. (A) Images amusement glioblastoma cells (green) stay labelled with CPN 680s (orange) successful a highly proliferating situation from azygous cells to a tumour mass. (B) Images were taken astatine 40 times magnification to corroborate CPNs remained wrong tumour cells. Images taken successful collaboration with the University of Liverpool. Image Credit: University of Liverpool
You person collaborated successful the past and proceed to enactment with antithetic universities and researchers connected progressive projects. Could you delight archer america astir immoderate of the probe you are supporting with your CPNs currently?
For instance, we person images successful the fig supra of bowel crab cells, colorectal cells, produced with Leeds University aesculapian school. When you effort to extract a tumor during surgery, defining the tumor borderline possesses issues and determination is the hazard of taking excessively small and risking the crab coming backmost oregon taking excessively overmuch and past causing harm to the patient. If you tin truly specify the tumor and the tumor margins, you tin amended surgical outcomes and besides adjacent prevention wealth successful the long-run. This is thing our particles are capable to bash with imaging technology. Professor David Janes astatine Leeds aesculapian schoolhouse has been a protagonist of america with this task and ongoing projects, and we've got a mates successful the pipeline with him arsenic well.
ICG is simply a objective imaging reagent that is utilized successful surgeries for imaging tumors and truthful on. It's successful the near-infrared, but it has a batch of drawbacks. It has to beryllium kept chill astatine 4 degrees, you indispensable person a definite magnitude of mentation clip to usage it, and if you don't usage it wrong a definite fig of hours it becomes toxic and quenches successful blood. That means it really reduces the signal. With Liverpool University, we precocious finished a task that did a implicit examination betwixt CPNs and ICG successful rodent models, and we were disconnected the scale. That probe volition beryllium published aboriginal this year, and what we'd similar to bash is instrumentality that probe further down the enactment of objective imaging.
We besides person different task going connected astatine the infinitesimal astatine Liverpool University sponsoring a Ph.D. student. They are doing a batch of enactment with stem cells and they've been utilizing our particles to way these cells successful chick embryos. The thought present is that, due to the fact that our particles are truthful agleam and stable, you tin way the cells implicit weeks and months, whereas different dyes would slice aft a fewer hours.
Finally, determination is an country of probe we're exploring astatine the infinitesimal looking astatine utilizing infrared particles connected lateral travel tests. By doing that, we efficaciously trim the inheritance sound to zero, further expanding sensitivity implicit and supra what we tin already do.
Over the adjacent decade, are determination immoderate presently untapped fields oregon applications that you would similar to attack with your particle technology?
When we were looking astatine the polymers for infrared particles, we screened a batch of them and recovered immoderate gave disconnected IR emissions and immoderate gave disconnected nary astatine all. When we discovered this we wanted to cognize why, arsenic that vigor has to spell determination to transportation and alteration state. It transpired that they weren’t giving disconnected infrared, but were giving disconnected vigor - much than a shortwave c nanotube.
CPN 510B linked to anti-carcinoembryonic antigen (CEA) affimer targeting colorectal crab cells, imaged by the University of Leeds
Shortwave c nanotubes person imaginable applications successful photothermal crab therapies, truthful we've got the imaginable to look further down the enactment astatine a CPN particle with an antibody to people a tumor cell. If you excite it astatine the close IR wavelength, (because it's infrared, it'll penetrate the tissue), you tin termination it with vigor alternatively of chemotherapy.
How revolutionary are CPNs for the aesculapian and beingness sciences industries?
The imaginable is vast. With respect to diagnostics and lateral flow, successful 10 years time, I deliberation they volition beryllium the caller standard, delivering laboratory sensitivity successful minutes astatine the constituent of care.
We similar to telephone it lateral travel 4.0 due to the fact that lateral flows have always been astir latex beads, golden nanoparticles, and europium. We've present got a caller reagent that tin truly stroke distant the diagnostics manufacture successful presumption of sensitivity. Looking further ahead, we person thing that could importantly amended fluorescent-guided surgery, amended diligent outcomes, and supply an alternate to chemotherapy successful the signifier of Photodynamic Therapy.
We've taken existing technologies, OLED polymers successful TV screens, which person been astir for decades, and repurposed them for biologic applications with highly breathtaking results and possibilities.
More from MEDICA 2022: Connecting the Field of Medicine astatine MEDICA
About Andy Chaloner
Andrew has coordinated and driven Stream Bio from its origins arsenic a ammunition company, to the constituent wherever its caller innovative materials exertion and products are connected the market. He is an entrepreneur, (not a scientist), an ex-military aviator and Royal Naval Officer with a beardown involvement successful science, and an arsenic beardown inheritance successful subject operations. This translates into extended personnel, task and logistical absorption skills wrong the biotech sector. On retiring from the Royal Navy Andrew moved into commercialized aviation, but it was ever his intention to determination into concern and has been progressive successful a fig of entrepreneurial projects
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