Rapid thermal cycling for sample analyses and processing

Abstract

Apparatus and method for thermal processing of nucleic acid in a thermal profile is provided. The apparatus employs a reactor holder for holding reactor(s) each accommodating reaction material containing the nucleic acid. The apparatus comprises a first bath; and a second bath, bath mediums in the baths being respectively maintainable at two different temperatures T HIGH and T LOW ; and a transfer means for allowing the reactor(s) to be in the two baths in a plurality of thermal cycles to alternately attain: a predetermined high target temperature T HT , and a predetermined low target temperature T LT , while the apparatus adapts to a temperature-offset feature defined by at least one condition from the group consisting: a) the T HT is lower than the T HIGH , b) the T LT is higher than the T LOW , and c) the conditions at a) and b).

1 . An apparatus for thermal processing of nucleic acid in a thermal profile, the apparatus employing a reactor holder for holding a reactor, wherein the reactor is configured to accommodate a reaction material containing the nucleic acid, the apparatus comprising:
 two baths including a first bath and a second bath;   wherein bath mediums in the two baths are configured to be maintainable at two different temperatures T HIGH  and T LOW , and   a transfer means configured for keeping the reactor to be in the two baths in a plurality of thermal cycles to alternately attain:
 a predetermined high target temperature T HT , and 
 a predetermined low target temperature T LT , 
 while the apparatus adapts to a temperature-offset feature defined by at least one condition selected from the group consisting of
 a) the T HT  is lower than the T HIGH , and 
 b) the T LT  is higher than the T LOW ; 
 
   the transfer means being operable by at least one mode selected from the group consisting of:   a temperature guided motion controlling means (TeGMCM) operable based on a real-time temperature as sensed by a reactor temperature sensor during thermal cycling,   and
 a time guided motion controlling means (TiGMCM) operable based on time-periods for which the reactor are allowed to be in the two baths; 
 the bath mediums in the two baths are in gaseous form, liquid form, solid form, powder form or combination thereof. 
   
     
     
         2 . The apparatus according to  claim 1 , wherein, the TiGMCM is configured to be calibrated for the time-periods. 
     
     
         3 . The apparatus according to  claim 1  further comprising a third bath, wherein a bath medium of the third bath is configured to be maintainable at a medium temperature T MEDIUM , wherein the transfer is configured for keeping the reactor to be in the third bath to attain a predetermined medium target temperature T MT , and the T MEDIUM  is equal to the T MT  or offset from the T MT . 
     
     
         4 . The apparatus according to  claim 1  further comprising
 a fourth bath, wherein a bath medium of the fourth bath is configured to be maintainable at a temperature T AP  to perform an additional process for the reactor before the thermal cycling, the additional process being one selected from the group consisting of 
 
       a) reverse transcription-polymerase chain reaction (RT-PCR), 
       b) hot start process and 
       c) isothermal amplification reaction, 
       wherein, the transfer means is configured for keeping the reactor to be in the fourth bath to attain an additional process target temperature T APT , the T AP  is equal to the T APT  or offset from the T AP . 
     
     
         5 . The apparatus according to  claim 1 , wherein the bath medium in the first bath is maintainable above 100 degrees Celsius. 
     
     
         6 . The apparatus according to  claim 1 , wherein the bath medium in the second bath is maintainable below room temperature. 
     
     
         7 . The apparatus according to  claim 1 , where the transfer means is calibrated to initiate lift-off of the reactor from the two baths when the reactor reaches a first lift-off temperature that is lower than the T HT  and a second lift-off temperature that is higher than the T LT , in order to compensate for operational electro-mechanical delays unwantedly causing over heating or over cooling of the reactor. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . The apparatus according to  claim 1 , wherein, a first offset between the T HIGH  and the T HT  is within a range of 1-400 degree Celsius and a second offset between the T LOW  and the T LT  is within a range of 1-100 degree Celsius. 
     
     
         15 . The apparatus according to  claim 1 , wherein, the bath medium in the first bath is a first liquid added to a second liquid, a boiling point of the second liquid being higher than a boiling point of the first liquid. 
     
     
         16 . The apparatus according to  claim 15 , wherein, a boiling point of a mixture of the first liquid and the second liquid is higher than 100 degree Celsius. 
     
     
         17 . The apparatus according to  claim 1  further comprising bath covers on the two baths, an opening on the covers for keeping the reactor to be in the two baths and closing after the reactor is removed from the two baths. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . A method for thermal processing nucleic acid in a thermal profile, comprising:
 employing a reactor holder for holding a reactor, wherein, the holding reactor accommodates, reaction material containing the nucleic acid;   employing an apparatus comprising two baths including a first bath and a second bath;   maintaining bath mediums in the first bath at temperature T HIGH  and in the second bath at temperature T LOW ; and   employing a transfer means in the apparatus to keep the reactor to be in the two baths in a plurality of thermal cycles to alternately attain:
 a predetermined high target temperature T HT , and 
 a predetermined low target temperature T LT ; and 
   adapting to a temperature-offset feature defined by at least one condition selected from the group consisting of:   a) the T HT  is lower than the T HIGH , and   b) the T LT  is higher than the T LOW      the transfer means being operable by at least one mode selected from the group consisting of:   a temperature guided motion controlling means (TeGMCM) that is operable based on a real-time temperature as sensed by a reactor temperature sensor during thermal cycling, and
 a time guided motion controlling means (TiGMCM) that is operable based on time-periods for which the reactor are allowed to be in the two baths;
 the bath mediums in the two baths are in gaseous form, liquid form, solid form, powder form or combination thereof. 
 
   
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The method according to  claim 21  further comprising maintaining the bath medium in the first bath above 100 degrees Celsius. 
     
     
         25 . The method according to  claim 21  further comprising maintaining the bath medium in the second bath below room temperature. 
     
     
         26 . The method according to  claim 21  further comprising calibrating the transfer means to initiate lift-off of the reactor from the two baths when the reactor reaches a first lift-off temperature that is lower than the T HT  and a second lift-off temperature that is higher than the T LT  to compensate for operational electro-mechanical delays unwantedly causing over heating or over cooling of the reactor. 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . The method according to  claim 21  further comprising
 adding a second liquid to a first liquid in the bath medium in the first bath, a boiling point of the second liquid being higher than a boiling point of the first liquid. 
 
     
     
         35 . The method according to  claim 34 , wherein, a boiling point of a mixture of the first liquid and the second liquid is higher than 100° C. 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . (canceled)