MICA_Consolidated_Lightning_Round_Slides.pptx

Wafer-scale Fabrication of Functional DNA Origami Devices

Spatial control of organic and inorganic materials on the 1–100nm scale

Integrated with electron beam (or photo-) lithography for wafer-scale, scalable fabrication

Fabrication on silicon dioxide, aluminum nitride, etc. for functional devices

Long-term, environmental stability via silica-based encapsulation

Prof. Mark Bathe Biological Engineering, MIT mbathe@mit.edu

Multi-channel Bioreactor Microsystem for Aviation Fuel Synthesis Susie Dai & Zheng Yan, University of Missouri, sydai@missouri.edu

1. Mass transfer limits substrate utilization and product removal

2. Enzyme stability and aggregation

3. Loss of function due to immobilization

4. Optimization of reaction conditions is time consuming

1. Immobilize enzymes and feed through substrates

2. Surface design and enzyme engineering

3. Affinity Tag expression for mobilization

4. Parallel multi channel reactors for real time monitoring and conditioning

Needs Solution Advantages

1. Achieve dynamic control and optimal reaction rates

2. System stability and robustness

3. Close to native state enzyme immobilization

4. A system to inform further improvement strategy

NBD

C4 C3 C1 C2

QC

C4 C3 C1 C2

1 2 3 4 5 6 7 8

Nanobiotronix Lab – Single Molecule Electrical Catalysis https://nanobiotronix.com/ Josh Hihath, jhihath@asu.edu

Artificial Enzymes Mechanically Control Electrode Separation Control the Applied Electric Field Monitor the Current through the Device Measure the Raman Spectra in Real-Time Induce Forbidden Reactions Directly Observe Transition States Control and Characterize Single-Molecule Reactions a c e g b d f h

Integrated Single-Molecule Electronic Catalysis

Gate/V -25 Time/s Current/nA

R

ΔS + V

ΔS + V2

VG1

VG2

Electrically Control Potential across a Molecular Device Apply Gate Voltages to Control Surface Charge and pH Reversibly Control Chemical Reactions On-Chip Obtain 10’s of Devices per Chip © 2025, J. Hihath, Patents Pending V G3

Ag+/Hg2+ Hg2+/Hg2+ Ag+/Hg2+ Ag+/Ag+

MIT Lincoln Laboratory MICA Areas of Expertise

Reaction Mixture In Catalyst Bed Flow Cell

Modulation Energy E(t) t t ~ min to hrs Catalyst-containing microfluidic flow cell Reaction Mixture Out System Performance Performance of coupled reactions Guide integration strategy

Catalyst Characterization Reversibility Efficiency Immobilization stability Spatial effects Modeling Reaction kinetics On/off transition dynamics Mass transport effects System Integration Multi-physics component integration

C(t)

In-Line Measurements

Raman Microscopy Continuous Mass Spec

Thermal, Rxn, Diffusion Modeling in mMicrofluidics

Integrated mMicrofluidics POCs: Rod Kunz; kunz@LL.mit.edu Brad Perkins; Bradford.perkins@LL.mit.edu

DARPA MICA Industry Day ‹#› 01/23/2024 Unclassified

Technical POC: Michael Switkes, mswitkes@draper.com

Teaming needs: Open to all Device Controlled Chemistry

Microfluidic Chemistry

3.5 5.5 8.0 Micro Optics Human Organ System DNA Monolayer

DNA

Electrode DNA Chip DNA µFluidic Device Surface Chemistry

2 nm -2 nm SiOx

Platinum

DNA

Nonprofit engineering Innovation at the intersection of government, academia, and industry Solving complex challenges in the national interest 2,300+ employees 12,000 ft2 BSL-2 laboratory, established operation in BSL-3 facility Cambridge MA headquarters with 12 other campuses across the country.

www.draper.com Reagent Storage/Release spatial control of pH Draper Expertise ASICs electronics software surface chemistry enzyme engineering synthetic chemistry micro-fluidics bio-informatics Molecular Device Fabrication Draper Overview gt3@berkeley.edu tilabberkeley.com Grigory Tikhomirov, assistant professor University of California Berkeley Electrical Engineering and Computer Sciences, Biophysics

DNA origami nanomachines compatible with CMOS and biology

1. Nanoscale self-assembly and fabrication:

2. Nanoscale machines for electronic control over biological activity including enzymatic catalysis https://www.nature.com/articles/nature24655 Capabilities:

Previous Work and Future Partners Nanofabrication for Biological Applications Katie Young (Katherine.young@gtri.gatech.edu) Facilities and Capabilities Cleanrooms: Class 100 inorganic and Class 1000 organic Materials Characterization Suite

SEM/TEM

Raman

AFM

XPS

Metrology

Plasma etch

Wafer bonding

Thin film deposition

Lithography We can provide fabrication and materials characterization if you can provide biomolecule expertise

Biotemplates for devices

Thin film nanopores

Well arrays for DNA synthesis

Citrine Informatics, External Research Department ERD Overview Research group within Citrine focused on publishable material informatics research Physics-based modeling, AI/ML, database development, automated experiments Recent work: polymers, nuclear waste storage, thermoelectrics, alloys, batteries, catalysts

CASE STUDY - SEQUENTIAL LEARNING FOR CATALYST SYNTHESIS OPTIMIZATION

Particle size distribution Average particle size Particle yield (scattering intensity) Utilization of machine learning to accelerate colloidal synthesis and discovery J. Chem. Phys. 154, 224201 (2021)

PI: Chris Tassone (SLAC) Contract #DE-AC02-76SF00515

ML – and computer controlled colloidal synthesis of nanoparticles and SAXS characterization 16 experiments to initialize ML, then uncertainty driven design

Confidential

Needs: (1) aqueous reactions that are DNA-friendly; (2) new ways to manipulate DNA structure on chip; (3) local photophysics on chip; (4) 3D multiplexing

(2) pH and Field-Driven Reconfiguration

Crystalline Nanoreactor Nanoscale channels

NH2

H2N

2.1 Å

C O

N

N C O

N

N

Ag+ cytosine ~2.3 Å

O O3P

O

O O

PO3

Metal-mediated DNA

Atomic design resolution Chip-based integration (Josh Hihath—ASU) Redox-active nanoclusters X-ray validation Highly-conductive electrical readout

DNA-Scaffolded, Electrically-Driven Catalysis Simon Vecchioni, Ruojie Sha, James W. Canary, Yoel Ohayon: Structural DNA Nanotech Lab at NYU

O O

PO3

N O O3P

O

N

N O O H

H3C

H

CN

photo product

H

H UV: 365 nm Photo crosslinking

140 nm

(1) Conductive Metallo-DNA Helices

(3) Solid-Phase Catalysis in DNA Nanostructures Transmetalation at applied gate bias (Josh Hihath—ASU) Local catalysis DNA triple helix forms at acidic pH Nanomechanical Proximity induced photo-catalysis Internal crystal interface engineering Size from nm to mm

ARZEDA’s NOBEL-PRIZE WINNING INTELLIGENT PROTEIN DESIGN TECHNOLOGY™ AI-DRIVEN DBTL CYCLE FOR NOVEL ENZYME DEVELOPMENT, FORWARD-INTEGRATED TO MANUFACTURING

Unmet market need

LEARN

Data-driven Deep Learning

DESIGN

Computational Design

TEST

Assay Protein Activity

BUILD

Synthetic DNA Arzeda commercial translation expertise

ARZEDA. // NON-CONFIDENTIAL

Optimization of expression host Commercial Titer

BioProcess & DSP Manufacturing process development

Scale-up (CMO)

Fermentations @ scale 1kL-100kL Novel function Stability in new environments Excellent manufacturability image1.png image28.png image29.png image38.png image39.png image40.png image41.png image42.png image43.png image44.png image45.png image46.png image47.jpg image30.png image48.jpg image49.jpg image50.png image51.png image52.png image53.png image54.png image55.png image31.png image56.png image57.png image58.png image59.png image60.png image61.png image62.png image63.jpg image64.png image65.png image32.png image66.png image67.png image68.png image69.png image70.jpg image71.png image72.png image73.png image74.png image75.png image33.jpg image76.png image34.png image35.png image36.png image37.png image77.jpeg image78.jpeg image79.jpg image80.png image81.jpeg image87.jpeg image88.jpeg image89.jpeg image90.emf image91.jpeg image82.png image83.jpeg image84.jpeg image85.png image86.png image92.png image93.png image94.png image95.png image96.png image97.jpeg image98.png image107.jpg image108.png image109.png image110.png image111.png image99.jpg image100.jpg image101.jpg image102.jpg image103.jpg image104.jpg image105.jpg image106.jpg image27.png image25.png image112.png image113.png image114.png image115.png image116.emf image117.png image118.png image119.png image120.emf image121.png image122.png image123.tif image124.png image125.png image126.png image127.tif image128.png image129.png image3.png image4.png image5.png image10.png