Injection needle and device
Several needle assemblies and intracellular delivery devices that are used for the delivery of prophylactic and/or therapeutic material (i.e., delivered agents) into a tissue of a subject are disclosed. Preferably, the needle assemblies and/or the intracellular delivery devices comprise needles and/or needle electrodes, which are disposed in an array (e.g., a Y-type array having three outer needles and a center needle), wherein each needle in the array has a closed end and a plurality of apertures along each needle barrel, and the apertures on the needle barrels of the outer needles of the array are positioned to deliver the delivered agent toward the apertures of the center needle and/or an adjacent needle, but not outside of the active zone defined by the area within the needle array and the apertures on the needle barrel of the center needle are positioned to deliver the delivered agent toward the outer needles.
1. An apparatus for intracellular delivery of a delivered agent comprising:
a hub comprising at least one electrical connector;
a plurality of needles connected to the hub, wherein each needle of the plurality of needles comprises:
a closed end;
a needle barrel; and
a plurality of apertures that are disposed on the needle barrel;
an electrode; and
an electrical power supply configured to generate an electric field at the electrode, wherein the electrical power supply is connected to the electrode through the at least one electrical connector, wherein the plurality of needles is arranged in an array of four needles arranged in a Y-type pattern comprising a center needle and three outer needles disposed around the center needle, wherein the center needle is a needle-electrode configured to apply a first polarity voltage, and the three outer needles are needle-electrodes, configured to apply a second polarity voltage; and
wherein the center needle comprises apertures along the needle barrel, which are configured to direct delivery of the delivered agent toward apertures that are present on each of the three outer needles and each of the three outer needles comprises apertures along the needle barrel, which are configured to direct delivery of a delivered agent toward apertures that are present on the center needle so as to generate an opposing direction of delivery of the delivered agent.
2. The intracellular delivery apparatus of claim 1 , wherein said needle-electrodes, are electrically connected to the electrical power supply and are configured to generate an electric field.
3. An intracellular delivery apparatus comprising:
a hub comprising at least one electrical connector:
a plurality of needles connected to the hub, wherein each needle of the plurality of needles comprises:
a closed end;
a needle barrel; and
a plurality of apertures that are disposed on the needle barrel;
an electrode; and
an electrical power supply configured to generate an electric field at the electrode, wherein the electrical power supply is connected to the electrode through the at least one electrical connector, wherein apertures on at least one needle barrel oppose the apertures on at least one other needle barrel wherein the plurality of needles is arranged in an array comprising a center needle and a plurality of outer needles disposed around the center needle, wherein the center needle comprises apertures along the needle barrel, which are configured to direct delivery of the delivered agent toward the outer needles and the outer needles comprise apertures along the needle barrel which are configured to direct delivery of a delivered agent toward the center needle so as to generate an opposing direction of delivery of the delivered agent;
a syringe in fluid communication with the hub; and
a delivery unit comprising:
a channel configured to receive the hub and the syringe;
a collar operable to fasten the syringe within the channel;
a handle, which operates to enclose the syringe and hub within the channel such that the closed ends of the needle barrels protrude from the channel and are available to engage a subject;
a charging element configured to be charged by the operation of the handle, the charging element coupled to a trigger and the syringe such that operation of the trigger releases the charging element and the charging element acts on the syringe, thereby displacing prophylactic and/or therapeutic material out of the syringe; and
an electrical port configured to mate with the electrical connector on the hub of the intracellular delivery apparatus thereby establishing electrical contact between the electrical power supply and the electrodes and/or needle-electrodes.
4. The intracellular delivery apparatus of claim 1 , wherein the hub is a pocket hub, comprising an individual reservoir of a delivered agent for each needle or needle electrode.
5. The intracellular delivery apparatus of claim 1 , wherein the hub comprises a single reservoir of a delivered agent for each needle or needle-electrode.
6. The intracellular delivery apparatus of claim 1 , wherein at least one needle of the plurality of needles is at least partially laminated with an electrically non-conductive material.
7. The intracellular delivery apparatus of claim 1 , further comprising an electrical power supply controller configured to control generation of the electric field.
8. The intracellular delivery apparatus of claim 7 , wherein controlling generation of the electric field comprises controlling one or more of a pulse voltage, polarity of the needle-electrodes, a number of pulses, a pulse pattern, or a pulse duration.
9. The intracellular delivery apparatus of claim 3 , wherein the charging element is a spring configured to be compressed by the operation of the handle and configured to decompress upon operation of the trigger or when activated by an electrically operated transducer.
10. The intracellular delivery apparatus of claim 1 , wherein the electric field applied at the electrode and/or needle electrodes is commutating.
11. The intracellular delivery apparatus of claim 3 , wherein the delivery unit is configured to control injection speed.
12. The intracellular delivery apparatus of claim 3 , wherein the delivery unit is configured to control injection pressure.
13. A method of nucleic acid immunization comprising:
providing the intracellular delivery apparatus of claim 1 ;
providing a voltage source;
inserting a plurality of needles and a plurality of electrodes or a plurality of
needle-electrodes of the intracellular delivery apparatus into a tissue of a subject;
displacing a nucleic acid through the plurality of apertures on the plurality of needles or the plurality of needle-electrodes and into the tissue of the subject; and
applying an electric field to the tissue of the subject.
14. The method of claim 13 , wherein the nucleic acid immunization comprises introduction of a polynucleotide encoding a hepatitis antigen.
15. The method of claim 14 , wherein the hepatitis antigen is a hepatitis C virus (HCV) antigen.
16. The method of claim 15 , wherein the HCV antigen comprises NS 3 .
17. A method of nucleic acid immunization comprising:
providing the intracellular delivery apparatus of claim 3 ;
providing a voltage source;
inserting a plurality of needles and a plurality of electrodes or a plurality of needle-electrodes of the intracellular delivery apparatus into a tissue of a subject;
displacing a nucleic acid through the plurality of apertures on the plurality of needles or the plurality of needle-electrodes and into the tissue of the subject; and
applying an electric field to the tissue of the subject.