Co-incubating confined microbial communities
This invention provides devices and methods that enable co-incubation of microorganisms. Also provided are methods of making such devices for co-incubation of microorganisms, and various applications of such devices.
1. An ingestible capsule or pill structured to include a first area containing a first microorganism and a second area containing a second microorganism, and a barrier between the first and the second areas, the barrier being impermeable to the first microorganism and the second microorganism and permeable to molecules and fluid, and wherein the areas are separated by a distance x, the distance x is selected to define a space structured to minimize competition for nutritive substances between the first and second microorganisms while allowing exchange of chemicals between the first and second microorganism, with the microorganisms unable to commingle in the ingestible capsule or pill and wherein the first organism performs a function differently than it would if the second microorganism was absent and wherein the first and second microorganisms are bacteria, protozoa, viruses, or fungi.
2. The ingestible capsule or pill of claim 1 , wherein the distance x is between about 50 μm and about 500 μm.
3. The ingestible capsule or pill of claim 1 , wherein the ingestible capsule or pill is a bead or a gel.
4. The ingestible capsule or pill of claim 1 , wherein at least one microorganism produces a therapeutic substance in the presence, but not absence, of at least another microorganism.
5. The ingestible capsule or pill of claim 1 , wherein at least one of the first and second microorganisms degrades an undesirable substance in the intestinal tract of the patient in the presence, but not absence, of at least the other of the first and second microorganisms.
6. The ingestible capsule or pill of claim 1 , wherein the ingestible capsule or pill comprises two or more gel beads.
7. The ingestible capsule or pill of claim 1 , wherein the first microorganism produces a first nutrient and the second microorganism produces a second nutrient and the distance x is calculated by numerically solving equations (1), (2) and (3):
Production
A
,
alpha
=
∂
A
alpha
∂
t
=
k
2
*
A
alpha
3
*
(
B
alpha
(
L
)
)
3
(
k
2
+
A
alpha
3
)
*
(
k
3
+
(
B
alpha
(
L
)
)
3
)
*
S
alpha
(
A
alpha
,
B
alpha
,
t
)
(
1
)
Consumption
A
,
alpha
=
∂
A
alpha
∂
t
=
k
4
*
A
alpha
*
S
alpha
(
A
alpha
,
B
alpha
,
t
)
(
2
)
Consumption
A
,
beta
=
∂
[
A
]
beta
∂
t
=
k
5
*
[
A
beta
]
(
L
)
*
S
beta
(
[
A
]
beta
,
[
B
]
beta
,
t
)
(
3
)
wherein L is distance x; A is the first nutrient; B is the second nutrient, alpha is the first microorganism; and beta is the second microorganism.
8. The ingestible capsule or pill of claim 7 , wherein the Production A,apha is equal to the sum of Consumption A,alpha and Consumpton A,beta .
9. The ingestible capsule or pill of claim 1 , wherein the first microorganism and the second microorganism form within a synthetic microbial community.
10. The ingestible capsule or pill of claim 9 , wherein the first microorganism and the second microorganism are synthrophic microorganisms.
11. The ingestible capsule or pill of claim 1 , wherein the ingestible capsule or pill is a polymeric particle.
12. A synthetic droplet or particle structured to include a first and a second area separated by a distance x, the first area containing a first microorganism, the second area containing a second microorganism, and the first and the second microorganisms are environmentally incompatible, wherein the first and the second microorganisms are confined by barriers with pores, the pores having a size selected to
i) be not permeable to bacteria,
ii) allow diffusion of molecules and flow of fluid, and
iii) prevent commingling of the first and the second microorganisms within the synthetic droplet or particle, and wherein the first and second microorganisms are bacteria, protozoa, viruses, or fungi.
13. The synthetic droplet or particle of claim 12 , wherein the distance x defines a space structured to minimize competition for nutritive substances between the first and second microorganisms while allowing exchange of chemicals between the first and second microorganisms.
14. The synthetic droplet or particle of claim 12 , wherein the synthetic droplet or particle is an ingestible capsule.
15. The droplet or particle of claim 12 , wherein the barriers are a polycarbonate membrane.
16. An ingestible capsule for co-incubating microorganisms, comprising: a first compartment and a second compartment separated by a distance x and connected via a communication channel, through a barrier structure, wherein the first compartment contains a first microorganism confined within the first compartment by the barrier structure, and the second compartment contains a second microorganism confined within the second compartment by the barrier structure, the first microorganism performing a function differently that it would if the second microorganism was absent, wherein the barrier structure is impermeable to the first microorganism and the second microorganism and permeable to molecules and fluid and wherein the first and second microorganisms are bacteria, protozoa, viruses, or fungi.
17. The ingestible capsule of claim 16 , wherein the ingestible capsule comprises an upper layer and a lower layer, the upper layer comprising the communication channel, the lower layer comprising the first and the second compartments, and the upper layer and the lower layer separated by the barrier structure.
18. The ingestible capsule of claim 17 , wherein the upper and the lower layer comprise a material selected from the group consisting of a polymer, metal, glass, hydrogel, composite or inert material.
19. The ingestible capsule of claim 17 , wherein the barrier structure is positioned between the lower and the upper layers.
20. The device ingestible capsule of claim 16 , wherein the distance x defines a space configured to minimize comminglement between the first microorganism and the second microorganism while allowing exchange of chemicals between the first microorganism and the second microorganism.
21. The ingestible capsule of claim 16 , wherein the first microorganism produces a first nutrient and the second microorganism produces a second nutrient and the distance x is calculated by numerically solving equations (1), (2), and (3):
Production
A
,
alpha
=
∂
A
alpha
∂
t
=
k
2
*
A
alpha
3
*
(
B
alpha
(
L
)
)
3
(
k
2
+
A
alpha
3
)
*
(
k
3
+
(
B
alpha
(
L
)
)
3
)
*
S
alpha
(
A
alpha
,
B
alpha
,
t
)
(
1
)
Consumption
A
,
alpha
=
∂
A
alpha
∂
t
=
k
4
*
A
alpha
*
S
alpha
(
A
alpha
,
B
alpha
,
t
)
(
2
)
Consumption
A
,
beta
=
∂
[
A
]
beta
∂
t
=
k
5
*
[
A
beta
]
(
L
)
*
S
beta
(
[
A
]
beta
,
[
B
]
beta
,
t
)
(
3
)
wherein L is distance x; A is the first nutrient; B is the second nutrient, alpha is the first microorganism; and beta is the second microorganism.
22. The ingestible capsule of 16 , wherein the distance x is between about 50 μm and about 500 μm.
23. The ingestible capsule of claim 16 , wherein the first microorganism and the second microorganism form within a synthetic microbial community.
24. The ingestible capsule of claim 16 , wherein the barrier structure is positioned between the compartments and the communication channel.
25. The ingestible capsule of claim 16 , the ingestible capsule comprises at least two gel beads.
26. A synthetic droplet or particle structured to include a first area containing a first microorganism, a second area containing a second microorganism and a barrier between the first and second areas, the first and second microorganisms being environmentally incompatible and the barrier being impermeable to the first microorganism and the second microorganism and permeable to molecules and fluid, wherein the areas are separated by a distance x, the distance x is selected to define a space structured to minimize competition for nutritive substances between the first and second microorganisms while allowing exchange of chemicals between the first and second microorganisms, with the microorganisms unable to commingle in the synthetic droplet or particle and wherein the first and second microorganisms are bacteria, protozoa, viruses, or fungi.
27. The synthetic droplet or particle of claim 26 , wherein the synthetic droplet or particle is an ingestible capsule or pill.
28. The synthetic droplet or particle of claim 26 , wherein the synthetic droplet or particle comprises two or more gel beads.
29. The synthetic droplet or particle of claim 26 , wherein the distance x is between about 50 μm and about 500 μm.
30. The synthetic droplet or particle of claim 26 , wherein the first microorganism is aerobic and the second microorganism is anaerobic.
31. The synthetic droplet or particle of claim 26 , wherein the first microorganism and the second microorganism have different growth rates.
32. The synthetic droplet or particle of claim 26 , wherein at least one of the first and second microorganisms produces a therapeutic substance in the presence, but not absence, of at least the other microorganism.
33. The synthetic droplet or particle of claim 26 , wherein at least one of the first and the second microorganism degrades an undesirable substance in an intestinal tract of a patient in the presence, but not absence, of at least the other of the first and the second microorganisms.