How will our product be used?
Our final product will be presented in two capsules. One capsule is an enteric capsule containing our modified bacteria, while the other capsule is a UV light radiator to trigger the bacteria synthesis what we want in the human small intestine. All the size of the capsules are designed as small as possible for people to swallow. The enteric capsule will dissolve in the small intestinal environment to allow the release of engineered bacteria. The UV light radiator is indigestible, therefore after the therapy, the patient just needs to excrete it outside the body. The shell of the UV light radiator capsule is non-toxic and harmless to prevent any damage to the body caused by the UV light radiator capsule.
Hiding in an enteric capsule, the bacteria will be able to enter the human small intestine without causing damage to the human body. When the capsule reached the small intestine, it releases the bacteria. UV light will be radiated by a capsule automatically when it reaches the place where the bacteria are dropped. The UV light will last only for few seconds, to prevent the UV light from damaging human intestinal cells, just to trigger the bacteria to synthesis the outer membrane vesicles, which carry anti-cancer drugs. The antigen presented on the outer membrane vesicle will than bind with the antigen receptor of the immune cells in the small intestine, releasing the anti-cancer drugs directly to the intestinal immune cells.
Improve on machine vision system
We trained a convolutional neural network to cognise the location of peyer's patches We used the pictures with open access, which were collected during real gastro- and colonoscopy examinations at a Hospital in Norway and partly labeled by experienced gastrointestinal endoscopists. The dataset contains 110,079 images and 374 videos where it captures anatomical landmarks and pathological and normal findings giving in total around 1 million images and video frames. However, the real accuracy of our capsule need to be tested through real world trials . Therefore, collaboration with hospitals is needed. We also need to ensure there is no ethical concern. Our model might also can be designed to aim to peyer's patches , which is the region contaion high density if immune cells.
[1]Edna Filipa Pais Soares and Olga Maria Fernandes Borges, Oral Vaccination Through Peyer's Patches: Update on Particle Uptake, Current Drug Delivery
Improved on hardware-reduce the size
The size of LED capsule prototype we designed is still too large than the capsule endoscope on the market.Fig1 and 2.
However, the micro controler module we used is too large which will take a lot of space, by change to another model, the PCB could be much smaller.
Improve SulAp through direct evolution
Initial planA:
LexA-binding sequences (LBS) were mutated, evolved and screened by similar exponential ligand enrichment (SELEX) and chromosomal immunoprecipitation-high-throughput sequencing (ChIP-seq) techniques. That is, LBS mutation library was randomly generated, and the sequence with high binding strength was selected as the next error-prone PCR template. LBS with stronger binding effect was obtained after several post cycles, so as to design a new SulAp promoter.
Plan B:
Nucleic acid protein interaction simulation was performed by computer, all possible mutations were scored, and high-score sequences were used for direct experiments.