Engineers connect bacteria to create living transistors

Amazing stuff! Are we getting closer to artificial biological intelligence? You bet!

The human brain is a lot more energy efficient than machine learning & artificial intelligence. The human brain does not need a voracious water and energy consuming data center!

"MIT researchers have engineered bacteria that can function as transistors, allowing the team to create living “circuit boards” that can be printed onto a growth medium in a Petri dish. ...

The research team designed two different transistors, along with three bacterial strains that relay information between the transistors, giving them the building blocks they need to design nearly any type of circuit. In a new study, they used these cells to create circuits that can add two or three inputs, or send one input to a specific location in the circuit. ..."

From the abstract:

"The multicellular forms and functions seen in biology are controlled by cellular communication and collective computation.

Reprogramming natural systems is difficult because they comprise many signaling molecules connecting a web of regulatory networks within cells.

Here we apply principles from pass transistor logic (PTL) to design bacteria that can be easily reconfigured to perform computations on a solid surface. Strains of Pantoea agglomerans were built to encode two transistors (N-type and P-type) whose inputs and outputs are small molecules. They are connected by three relay strains that convert molecular diffusion to unidirectional flow.

To build circuits, an acoustic liquid handler prints patterns of these five strains on a surface.

By changing the pattern, not requiring any genetic changes, different operations are implemented, including multi-input multioutput logic, demultiplexor, half-adder and full-adder.

This work demonstrates that only five cell types, each encoding a simple operation, can be scaled to create complex computational operations."

MIT engineers connect bacteria to create living transistors | MIT News | Massachusetts Institute of Technology "By wiring together colonies of these bacteria, the researchers built circuits that can perform complicated calculations."

Living circuit boards built by printing bacterial transistors (no public access)

Tiny implantable, high density ‘cell factories’ produce drugs inside the body

Good news!

"Tiny devices containing cells engineered to continuously produce drugs could one day deliver medicines from inside the body without requiring patients to remember to administer doses.

Researchers have designed a device called hybrid oxygenation bioelectronics system for implanted therapy, or HOBIT, in a step towards realising this goal.

The system hides genetically-engineered cells from the immune system while producing its own oxygen and nutrients to keep the cells alive.

It contains a cell chamber to house the cells, an electrochemical device to generate oxygen by splitting water molecules and electronics and a battery to regulate oxygen production while wirelessly communicating with external devices.

In a proof-of-concept study the team engineered cells to produce an anti-HIV antibody, a GLP-1-like peptide used to treat type 2 diabetes and leptin, a hormone that regulates appetite and metabolism. They implanted the devices under the skin of rats and monitored drug levels in the animals’ bloodstreams for 30 days.

Levels remained stable across the study period. About 65% of the cells were still viable by the end of the experiment. ..."

From the highlights and abstract:

"The bigger picture

.... The difficulty lies in making cells potent enough to be clinically relevant and easy to administer. The hybrid oxygenation bioelectronics system for implanted therapy (HOBIT) device solves these problems: supplemental oxygen is produced at the site of implant and enables a greater density of cells in the subcutaneous space, allowing a minimally invasive procedure to deliver a complex biologic regimen in a proof-of-concept model. From here, the platform can be expanded to target a variety of diseases or cell types to maximize efficacy and feasible translation.

Highlights

• A fully implantable, subcutaneous device enables high-density cell therapy

• Complex biologic therapy regimens are enabled with the HOBIT design

• The HOBIT device demonstrates power-efficient, subcutaneous oxygen generation

Summary

Cell therapy shows promise for sustained delivery of therapeutics, allowing a single dose to replace repeated injections and lasting many months to years. As cells are typically delivered systemically, a natural progression of cell therapy is to miniaturize and compact the cells into a single device. However, the nutrient requirements, coupled with practical limits on device size, limit its application. In addition, while the subcutaneous space presents a convenient location for implantation, oxygen supply is limited and restricts the density of effective cell therapy.

To address this problem, we designed and validated a wireless, fully implantable platform to produce local oxygen and increase the maximum cell density. We demonstrate that encapsulated cells with a density of 60 million cells per mL are viable in our device for 31 days in vivo. This technology has the potential to serve as a platform for cell therapy, allowing clinically relevant doses with minimally invasive implants."

Implantable ‘cell factories’ produce drugs inside the body | News | ConnectSci

Design of a wireless, fully implantable platform for in-situ oxygenation of encapsulated cell therapies (no public access)

Graphical abstract

Subcellular Circulatronics offers surgery-free brain treatment breakthrough

Good news! Amazing stuff! This could be a breakthrough indeed!

"A team of researchers at Massachusetts Institute of Technology (MIT) has been refining and combining several advanced technologies over the past six years to create a revolutionary platform to treat a vast array of neurological diseases and mental illnesses. ...

It's called Circulatronics, and the idea is to use a fusion of electronics and biological transport to autonomously implant bioelectronics within the body – completely avoiding the need for surgery to enable modern forms of treatment.

The tech is centered around using targeted electrical stimulation aimed at the brain for various conditions. In recent years, this approach has been applied to treating depression, Alzheimer’s disease, Multiple sclerosis, and brain tumors. ...

it involves sub-cellular sized wireless electronic devices (SWED) that can be delivered to your brain via a jab in the arm. Once these tiny chips have been injected, they can autonomously implant themselves on target regions in the brain, and power themselves as they deliver electrical stimulation to the affected areas. ..."

"... Moreover, because the electronic devices are integrated with living, biological cells before being injected, they are not attacked by the body’s immune system and can cross the blood-brain barrier while leaving it intact. This maintains the barrier’s crucial protection of the brain. ..."

From the abstract:

"Bioelectronic implants for brain stimulation are used to treat brain disorders but require invasive surgery. To provide a noninvasive alternative, we report nonsurgical implants consisting of immune cell–electronics hybrids, an approach we call Circulatronics.

The devices can be delivered intravenously and traffic autonomously to regions of inflammation in the brain, where they implant and enable neuromodulation, circumventing the need for surgery.

To achieve suitable electronics, we designed and built subcellular-sized, wireless, photovoltaic electronic devices that harvest optical energy with high power conversion efficiency.

In mice, we demonstrate nonsurgical implantation in an inflamed brain region, as an example of therapeutic target for several neural diseases, by employing monocytes as cells, covalently attaching them to the subcellular-sized, wireless, photovoltaic electronic devices and administering the resulting hybrids intravenously.

We also demonstrate neural stimulation with 30-µm precision around the inflamed region. Thus, by fusing electronic functionality with the biological transport and targeting capabilities of living cells, this technology can form the foundation for autonomously implanting bioelectronics."

MIT's Circulatronics offers surgery-free brain treatment breakthrough

New therapeutic brain implants could defy the need for surgery (original news release) "MIT researchers created microscopic wireless electronic devices that travel through blood and implant in target brain regions, where they provide electrical stimulation."

A nonsurgical brain implant enabled through a cell–electronics hybrid for focal neuromodulation (open access)

Fig. 2: Characterization of subcellular-sized electronics with optical remote control.

Fig. 3: Autonomous implantation of wireless bioelectronics in the brain.

‘Biohybrid’ device could restore function in paralysed limbs

Good news!

"... Previous attempts at using neural implants to restore limb function have mostly failed, as scar tissue tends to form around the electrodes over time, impeding the connection between the device and the nerve. By sandwiching a layer of muscle cells reprogrammed from stem cells between the electrodes and the living tissue, the researchers found that the device integrated with the host’s body and the formation of scar tissue was prevented. The cells survived on the electrode for the duration of the 28-day experiment, the first time this has been monitored over such a long period. The researchers say that by combining two advanced therapies for nerve regeneration – cell therapy and bioelectronics – into a single device, they can overcome the shortcomings of both approaches, improving functionality and sensitivity. ...
The researchers designed a biocompatible flexible electronic device that is thin enough to be attached to the end of a nerve. A layer of stem cells, reprogrammed into muscle cells, was then placed on the electrode. This is the first time that this type of stem cell, called an induced pluripotent stem cell, has been used in a living organism in this way. ..."

From the abstract:

"The development of neural interfaces with superior biocompatibility and improved tissue integration is vital for treating and restoring neurological functions in the nervous system. A critical factor is to increase the resolution for mapping neuronal inputs onto implants. For this purpose, we have developed a new category of neural interface comprising induced pluripotent stem cell (iPSC)–derived myocytes as biological targets for peripheral nerve inputs that are grafted onto a flexible electrode arrays. We show long-term survival and functional integration of a biohybrid device carrying human iPSC-derived cells with the forearm nerve bundle of freely moving rats, following 4 weeks of implantation. By improving the tissue-electronics interface with an intermediate cell layer, we have demonstrated enhanced resolution and electrical recording in vivo as a first step toward restorative therapies using regenerative bioelectronics."

‘Biohybrid’ device could restore function in paralysed limbs Researchers have developed a new type of neural implant that could restore limb function to amputees and others who have lost the use of their arms or legs.

Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics (open access)

Fig. 1. A biohybrid peripheral neural interface.

Growing Electronics Inside the Brain in live zebra fish and leeches

Amazing stuff! I could use a better brain! 😊 This seems to be early stage research!

"Bioelectronics can be made directly inside the brains of live animals by injecting a cocktail of molecules that can transform into electrically conductive gel, a new study finds.

Swedish scientists have created bioelectronics in live zebra fish and leeches with this new technique. In the long term, the ability to turn any living tissue into electronic matter could make it possible to fabricate microchips in live organisms, the researchers say. ...

The scientists developed a medley of molecules that, when injected into biological tissue, chemically reacted with naturally occurring compounds such as glucose and lactase to form an electrically conducting gel. (Before the injection, the cocktail is not electrically conductive.)

The Swedish researchers first created electronic roses in 2015. However, plant cells possess rigid walls that can serve as scaffolding to help electrodes form, whereas animal cells lack such structures. Creating a mixture of compounds that could form electronics in animals took years of work. ..."

"A recipe for in situ bioelectronic materials

There are challenges in making materials that are soft enough to be interfaced with living tissue but firm enough to be inserted into the body. Strakosas et al. bypassed this challenge by developing a route to the polymer in vivo (see the Perspective by Inal). They introduced a complex precursor system including an oxidase to generate hydrogen peroxide in situ, a peroxidase to catalyze oxidative polymerization, a water-soluble conjugated monomer, a polyelectrolyte with counterions for covalent cross linking, and a surfactant for stabilization. With this cocktail, the authors were able to induce polymerization and subsequent gelation in different tissue environments. Demonstrations include the ex situ fabrication of this conducting gel in zebrafish (brain, fin, and heart), in food samples (beef, pork, chicken, and tofu), and a proof of concept of in vivo stimulation of a leech nerve. ..."

From the abstract of the perspective:

"Electronic devices implanted into a tissue close to neurons of interest are meant to exchange signals with the nervous system. Such bioelectronic devices not only facilitate the study of neural communication, they can also hijack neural circuitry in a therapeutic approach known as bioelectronic medicine. The success of these applications relies on the robustness of the implanted devices and their compatibility with the body. Conventional bioelectronic devices have solid substrates that carry conducting films. Their rigidity can damage soft tissues and reduce an implant’s long-term performance. On page 795 of this issue, Strakosas et al. (1) address the mechanical mismatch between soft and wet biological matter and solid-state electronics and describe an approach that generates electronics directly inside a tissue without a substrate, causing little damage to the tissue."

From the abstract:

"Interfacing electronics with neural tissue is crucial for understanding complex biological functions, but conventional bioelectronics consist of rigid electrodes fundamentally incompatible with living systems. The difference between static solid-state electronics and dynamic biological matter makes seamless integration of the two challenging. To address this incompatibility, we developed a method to dynamically create soft substrate-free conducting materials within the biological environment. We demonstrate in vivo electrode formation in zebrafish and leech models, using endogenous metabolites to trigger enzymatic polymerization of organic precursors within an injectable gel, thereby forming conducting polymer gels with long-range conductivity. This approach can be used to target specific biological substructures and is suitable for nerve stimulation, paving the way for fully integrated, in vivo–fabricated electronics within the nervous system."

Growing Electronics Inside the Brain - IEEE Spectrum Experiments in live zebra fish and leeches may one day lead to growing microchips in living tissue

Perspective Turning tissues into conducting matter An electrically conducting soft polymer is synthesized within living tissue (no public access)

Researchers grow electronics directly inside living tissue

Metabolite-induced in vivo fabrication of substrate-free organic bioelectronics (no public access)