Open-Source Blueprint: PancreaCORE - The PDAC Ablation System

Document Status: PRIOR ART & TECHNICAL SPECIFICATION - Public Domain, CC0 1.0 Universal.
Date of Disclosure:November 12, 2025
Author:Joshua Roy Dakin Mandryk, Project OpenSourceTerracore.

Objective

To provide a complete, open-source blueprint for a curative, multi-modal therapeutic system for Pancreatic Ductal Adenocarcinoma (PDAC), designed to dismantle the tumor's defense systems and induce complete regression.

Core Thesis: The Simultaneous Multi-Front Assault

PDAC's lethality stems from its multi-layered defense. The PancreaCORE system executes a synchronized, in-situ attack on all three fronts within a single clinical procedure.

System Architecture & Procedure Workflow

The PancreaCORE is an integrated suite of devices used in a single, image-guided interventional procedure. The core platform is a modified Endoscopic Ultrasound (EUS) system.

Procedure Timeline: ~90-120 minutes.

1. Phase 1 (T=0-15 min): Mapping & Targeting via EUS-Guided Multi-Spectral Optoacoustic Tomography (MSOT).
2. Phase 2 (T=15-45 min): Stromal Breach via Targeted Pulsed Electro-Histotripsy (TPEH).
3. Phase 3 (T=45-60 min): Precision Lethality via Localized Multi-Agent Infusion (LMAI).
4. Phase 4 (T=60-90 min): Immune Activation via Biodegradable Immuno-Scaffold (BIS) Implant.


Phase 1: The Cartographer - EUS-Guided MSOT

Function & Rationale

To visualize the tumor's functional anatomy in real-time to guide targeted therapy.

Technical Specifications

· Base Platform: Standard EUS endoscope.
· Integrated MSOT Probe:
  · Technology: Multi-Spectral Optoacoustic Tomography.
  · Laser Source: Tunable OPO laser, pulses at 10 Hz.
  · Wavelengths: 680, 730, 760, 800, 850, 900 nm.
  · Ultrasound Detector: 64-element annular array.
· Output Variables & Algorithms:
  · Hypoxia Map: H_map = fNIRS_algorithm(SO2_680nm, SO2_730nm, SO2_760nm)
  · Vascular Density Map: V_map = OA_signal_amplitude(800nm)
  · Stromal Density Map: S_map = OA_signal_amplitude(900nm)

Phase 2: The Breacher - Targeted Pulsed Electro-Histotripsy (TPEH)

Function & Rationale

To physically disrupt the dense stromal barrier and permeabilize cancer cell membranes without thermal damage.

Technical Specifications

· Integrated EUS-TPEH Needle:
  · Material: Insulated 19-gauge needle with 1cm exposed conductive tip.
  · Electrodes: Bipolar configuration.
· Pulsed Electric Field (PEF) System:
  · Waveform: Biphasic, square-wave pulses.
  · Voltage: 1000 V/cm
  · Pulse Width: 100 µs per phase
  · Pulse Number: 80 pulses
  · Frequency: 1 Hz
· Coincident Histotripsy System:
  · Transducer: External, focused ultrasound transducer.
  · Frequency: 1 MHz
  · Peak Negative Pressure (PNP): 8 MPa
  · Pulse Duration: 5 cycles
  · Pulse Repetition Frequency (PRF): 1 Hz
· Synchronization: Histotripsy pulse delivered 200 µs AFTER the end of each PEF pulse.
· Targeting: Uses the S_map from Phase 1.

Phase 3: The Terminator - Localized Multi-Agent Infusion (LMAI)

Function & Rationale

To deliver a multi-mechanism, tumor-specific cytotoxic payload directly into the breached tumor.

Payload Formulation

The following cocktail is infused via the central lumen of the EUS-TPEH needle. Total volume: 10-20 mL.

Component Concentration Mechanism of Action
KRAS-G12D/V CRISPR-Cas13d LNPs 1.0 mg/mL Genetic Silencing: Degrades mutant KRAS mRNA.
NTR-Encoding Minicircle DNA 0.5 mg/mL "Suicide Gene": Expresses E. coli Nitroreductase (NTR).
Albumin-Bound Gemcitabine 10 mg/mL Cytotoxic Chemotherapy.
Albumin-Bound Paclitaxel 5 mg/mL Cytotoxic Chemotherapy.
PEGylated Hyaluronidase 50 U/mL Matrix Degradation: Degrades hyaluronic acid in stroma.
Tranexamic Acid (TXA) 10 mg/mL Anti-fibrinolytic: Prevents clotting.

Infusion Rate: 1 mL/min.

---

Phase 4: The Sentry - Biodegradable Immuno-Scaffold (BIS) Implant

Function & Rationale

To create a sustained, local source of immunostimulation, reversing immunosuppression and training the immune system for long-term surveillance.

Implant Formulation & Specifications

· Base Matrix: Thermosensitive Poloxamer 407 Hydrogel (25% w/v).
· Immunostimulatory Payload:
  · STING Agonist (cGAMP): 100 µM
  · IL-15 Superagonist (ALT-803): 50 µg/mL
  · Anti-PD-1 Nanobodies: 1 mg/mL
  · GM-CSF: 20 µg/mL
· Implantation: Injected into the treated tumor cavity after LMAI infusion. Gelates at body temperature.
· Degradation Time: 3-4 weeks.

Post-Procedure Activation Protocol

1. Day 1-5: Oral administration of the prodrug CB1954 begins. It is activated by the NTR enzyme within the tumor, creating a potent, localized cytotoxin.
2. Week 1-4: The BIS implant degrades, continuously releasing immunostimulants to drive a systemic anti-tumor immune response.

Integrated System Control & Safety Code

```python
# Pseudo-Code for PancreaCORE Master Control Sequence
def pancreacore_procedure(eus_needle, tumor_coordinates, stromal_map):
    
    # PHASE 1: MAPPING
    h_map, v_map, s_map = msot_cartographer.map_tumor(tumor_coordinates)
    
    # PHASE 2: STROMAL BREACH
    for target_zone in s_map.high_density_zones:
        eus_needle.position = target_zone
        for pulse in range(80):
            pef_system.deliver_pulse(voltage=1000, width=100e-6)
            time.sleep(0.200e-3) # 200 µs delay
            histotripsy_system.deliver_pulse(pnp=8e6, cycles=5)
            time.sleep(1.0) # 1 Hz PRF
    
    # PHASE 3: MULTI-AGENT INFUSION
    lmai_cocktail = prepare_cocktail(
        cas13d_lnp=1.0,
        ntr_mcdna=0.5,
        gemcitabine=10,
        paclitaxel=5,
        hyaluronidase=50,
        txa=10
    )
    eus_needle.infuse(lmai_cocktail, rate=1.0) # 1 mL/min
    
    # PHASE 4: IMMUNE SCAFFOLD IMPLANT
    bis_implant = prepare_hydrogel(
        poloxamer=25,
        cgamp=100e-6,
        il15_superagonist=50e-6,
        anti_pd1_nb=1.0,
        gm_csf=20e-6
    )
    eus_needle.infuse(bis_implant)

    print("PancreaCORE Procedure Complete. Initiate oral CB1954 protocol.")
```

Declaration of Prior Art & Sovereign Release

This document, the PancreaCORE PDAC Ablation System, its integrated methods, specific parameters, and formulations are hereby placed irrevocably into the public domain.

The cure for pancreatic cancer is no longer a secret. It is a recipe.
